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In early 2023, a new type of weight loss medication, Wegovy (semaglutide), was made available in Denmark. Both subsequent media coverage and public demand were huge. Wegovy is only available by prescription, primarily via general practitioners. However, there is very little knowledge about how healthcare professionals (HCPs) in general practice might deal with the great demand for and attention surrounding a new weight loss drug. The aim of this qualitative study was, therefore, to explore how Wegovy is managed and negotiated in general practice, particularly in terms of prescribing and follow-up. We conducted a focused ethnography study based on direct observation of consultations and both formal and informal interviews with seven doctors and four nurses from three general practices in Denmark. Using discourse analysis, we identified four central discourses revolving around trust in medicine, individual responsibility for health, the cost of weight loss medication, and the importance of shared decision-making. This study shows that the availability of a new, sought-after weight loss medication presents both opportunities and challenges for HCPs in general practice. The management of Wegovy involves numerous factors, including medical, economic, organizational, interpersonal and moral concerns., (© 2024 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: During the developmental transition from childhood to adulthood, young people living with type 1 diabetes (T1D) are more likely to take less care of their chronic disease. Alongside the developmental transition, young people with T1D also experience an organisational transition in which the care responsibility changes from a family-based approach in paediatric care to an individualised approach in adult care. Little is known from the perspective of the young people about what their interactions with the healthcare providers mean during these transitions., Aim: The aim of this study is to explore how young people living with T1D experience interactions with their care providers, and what it means for their developmental transition., Method: Semi-structured interviews with 10 respondents aged 18-20 living with T1D who were recruited from a youth outpatient diabetes clinic in Denmark. Recorded audio data were transcribed and analysed using an interpretative phenomenological analysis approach., Results: Young people experience continuity in the relationship with the diabetes nurse from the paediatric clinic and a personal patient-provider relationship with their well-known and new care providers. This creates a feeling of familiarity and contributes to a seamless transition. The young people express that becoming more involved in diabetes treatment increases their willingness to take more responsibility for their own health. They also express that care providers should support them in managing their diabetes and talk about sensitive topics., Conclusion: Continuity in the relationship with the diabetes nurse makes the transition from paediatric to adult care more satisfying and seamless. To support the developmental transition, care providers should gradually involve young people more in diabetes management and be supportive as they become more independent during the developmental transition., (© 2023 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

Background: Experiences over the last three decades of war have demonstrated a high incidence of traumatic brain injury (TBI) resulting in a persistent need for a neurosurgical capability within the deployed theater of operations. Despite this, no doctrinal requirement for a deployed neurosurgical capability exists. Through an iterative process, the Joint Trauma System Committee on Surgical Combat Casualty Care (CoSCCC) developed a position statement to inform medical and nonmedical military leaders about the risks of the lack of a specialized neurosurgical capability., Methods: The need for deployed neurosurgical capability position statement was identified during the spring 2021 CoSCCC meeting. A triservice working group of experienced forward-deployed caregivers developed a preliminary statement. An extensive iterative review process was then conducted to ensure that the intended messaging was clear to senior medical leaders and operational commanders. To provide additional context and a civilian perspective, statement commentaries were solicited from civilian clinical experts including a recently retired military trauma surgeon boarded in neurocritical care, a trauma surgeon instrumental in developing the Brain Injury Guidelines, a practicing neurosurgeon with world-renowned expertise in TBI, and the chair of the Committee on Trauma., Results: After multiple revisions, the position statement was finalized, and approved by the CoSCCC membership in February 2023. Challenges identified include (1) military neurosurgeon attrition, (2) the lack of a doctrinal neurosurgical capabilities requirement during deployed combat operations, and (3) the need for neurosurgical telemedicine capability and in-theater computed tomography scans to triage TBI casualties requiring neurosurgical care., Conclusion: Challenges identified regarding neurosurgical capabilities within the deployed trauma system include military neurosurgeon attrition and the lack of a doctrinal requirement for neurosurgical capability during deployed combat operations. To mitigate risk to the force in a future peer-peer conflict, several evidence-based recommendations are made. The solicited civilian commentaries strengthen these recommendations by putting them into the context of civilian TBI management. This neurosurgical capabilities position statement is intended to be a forcing function and a communication tool to inform operational commanders and military medical leaders on the use of these teams on current and future battlefields., Level of Evidence: Prognostic and Epidemiological; Level V., (Copyright © 2023 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Primary care providers see patients with obesity in general practice every day but may be challenged regarding communication about obesity. The research question of this study is: how do general practitioners and general practice staff and adult patients with obesity communicate about weight-related issues?, Methods: A scoping review approach was used, searching PubMed, Scopus and CINAHL for peer-reviewed studies - of both quantitative and/or qualitative study designs, and published between 2001 and 2021., Results: Twenty articles were included. The weight-related issues discussed were by far physical issues, and only one study mentioned psychosocial issues. Most of the included studies contained information on who initiates the communication, how the weight-related issues are addressed and handled, and also obstacles and challenges in relation to the communication. The studies lacked information of when the weight-related issues are addressed and differences in views and experiences when discussing weight-related issues in general practice., Conclusion: Studies with the main focus communication about obesity and overall health in general practice are needed. Findings also indicate, that non-stigmatizing communication tools and guidelines are needed on this area to promote these types of conservations., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

This review focuses on communication about weight-related issues with patients with obesity in general practice. Primary care providers still lack knowledge and tools to address and communicate about the topic of weight and weight-related issues - with focus on minimizing stigmatization and a person centered approach. A few communication tools on the topic have been developed but it seems that the use of those is limited, suggesting an urgent need for making a fast, easy and simple tool for the use in general practice.

Background: Over the last 20 years of war, there has been an operational need for far forward surgical teams near the point of injury. Over time, the medical footprint of these teams has decreased and the utilization of mobile single surgeon teams (SSTs) by the Services has increased. The increased use of SSTs is because of a tactical mobility requirement and not because of proven noninferiority of clinical outcomes. Through an iterative process, the Committee on Surgical Combat Casualty Care (CoSCCC) reviewed the utilization of SSTs and developed an expert-opinion consensus statement addressing the risks of SST utilization and proposed mitigation strategies., Methods: A small triservice working group of surgeons with deployment experience, to include SST deployments, developed a statement regarding the risks and benefits of SST utilization. The draft statement was reviewed by a working group at the CoSCCC meeting November 2021 and further refined. This was followed by an extensive iterative review process, which was conducted to ensure that the intended messaging was clear to senior medical leaders and operational commanders. The final draft was voted on by the entire CoSCCC membership. To inform the civilian trauma community, commentaries were solicited from civilian trauma leaders to help put this practice into context and to further the discussion in both military and civilian trauma communities., Results: After multiple revisions, the SST statement was finalized in January 2022 and distributed to the CoSCCC membership for a vote. Of 42 voting members, there were three nonconcur votes. The SST statement underwent further revisions to address CoSCCC voting membership comments. Statement commentaries from the President of the American Association for the Surgery for Trauma, the chair of the Committee on Trauma, the Medical Director of the Military Health System Strategic Partnership with the American College of Surgeons and a recently retired military surgeon we included to put this military relevant statement into a civilian context and further delineate the risks and benefits of including the trauma care paradigm in the Department of Defense (DoD) deployed trauma system., Conclusion: The use of SSTs has a role in the operational environment; however, operational commanders must understand the tradeoff between tactical mobility and clinical capabilities. As SST tactical mobility increases, the ability of teams to care for multiple casualty incidents or provide sustained clinical operations decreases. The SST position statement is a communication tool to inform operational commanders and military medical leaders on the use of these teams on current and future battlefields., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Objectives: The research question asked to what extent do self-rated performance scores of individual surgeons correspond to assessed procedural performance abilities and to peer ratings of procedural performance during a mass casualty (MASCAL) event?, Background: Self-assessment using performance rating scales is ubiquitous in surgical education as a proxy for direct measurement of competence. The validity and reliability of self-ratings as competency measures are susceptible to cognitive biases such as Dunning-Kruger effects, which describe how individuals over/underestimate their own performance compared to assessments from independent sources. The ability of surgeons to accurately self-assess their procedural performance remains undetermined., Methods: A purposive sample of military surgeons (N = 13) who collectively cared for trauma patients during a MASCAL event participated in the study. Pre-event performance assessment scores for 32 trauma procedures were compared with post-event self and peer performance ratings using F tests ( P < 0.05) and effect sizes (Cohen's d )., Results: There were no significant differences between peer ratings and performance assessment scores. There were significant differences between self-ratings and both peer ratings ( P < 0.001) and performance assessment scores ( P < 0.001). Effect sizes were very large for self to peer rating comparison (Cohen's d = 2.34) and self to performance assessment comparison (Cohen's d = 2.77)., Conclusions: The outcomes demonstrate that self-ratings were significantly lower than the independently determined assessment scores for each surgeon, revealing a Dunning-Kruger effect for highly skilled individuals underestimating their abilities. These outcomes underscore the limitations of self-assessment for measuring competence., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Maternal obesity is a global health concern that is associated with significant effects on both short- and long-term health of both mother and child. However, maternal lifestyle interventions tend to focus solely on diet and physical activity in ways that disembody and disengage the social context in which women live their lives., Aims: The aim of this study was to explore the lived experiences of maternal obesity and delve into how experiences of the body and motherhood affect women's motivation for participating in a postpartum lifestyle intervention., Method: A qualitative study using in-depth semi-structured interviews based on participant-generated photographs was used to allow the women to openly express their lived experiences of maternal obesity. The study emanated from a gynaecological department of a major Danish hospital, and five pregnant or postpartum women living with obesity participated. Interviews were audio recorded, transcribed and analysed using an Interpretive Phenomenological Approach., Results: The analysis identified an overall theme of ambivalence and four subthemes among the participating women. The themes reflected contrasting feelings where the obese body was simultaneously an arena for aesthetic failure, functional success and moral dilemmas. Experiences of weight stigma and moral accusations in healthcare settings further increased the women's sense of ambivalence and challenged their strong desire to lose weight., Conclusion: This study highlights an ambivalent and vulnerable situation of maternal obesity which makes moral sensitivity towards weight and body concerns crucial to consider in future maternal health interventions. Our data suggest that an emphasis on functionality and capability rather than aesthetics and measured ideals would be useful in providing care and support in postpartum lifestyle interventions for women living with obesity., (© 2021 Nordic College of Caring Science.)

Background: The Military Health System must develop and sustain experienced surgical trauma teams while facing decreased surgical volumes both during and between deployments. Military trauma resources may enhance local trauma systems by accepting civilian patients for care at military treatment facilities (MTFs). Some MTFs may be able to augment their regional trauma systems by developing trauma center (TC) capabilities. The aim of this study was to evaluate the geographical proximity of MTFs to the continental US (CONUS) population and relative to existing civilian adult TCs, and then to determine which MTFs might benefit most from TC development., Methods: Publicly available data were used to develop a list of CONUS adult civilian level 1 and level 2 TCs and also to generate a list of CONUS MTFs. Census data were used to estimate adult population densities across zip codes. Distances were calculated between zip codes and civilian TCs and MTFs. The affected population sizes and reductions in distance were tabulated for every zip code that was found to be closer to an MTF than an existing TC., Results: 562 civilian adult level 1 and level 2 TCs and 33 military medical centers and hospitals were identified. Compared with their closest civilian TCs, MTFs showed mean reductions in distance ranging from 0 to 30 miles, affecting populations ranging from 12 000 to over 900 000 adults. Seven MTFs were identified that would offer clinically significant reductions in distance to relatively large population centers., Discussion: Some MTFs may offer decreased transit times and improved care to large adult populations within their regional trauma systems by developing level 1 or level 2 TC capabilities. The results of this study provide recommendations to focus further study on seven MTFs to identify those that merit further development and integration with their local trauma systems., Level of Evidence: IV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Hemorrhage is the most common mechanism of death in battlefield casualties with potentially survivable injuries. There is evidence that early blood product transfusion saves lives among combat casualties. When compared to component therapy, fresh whole blood transfusion improves outcomes in military settings. Cold-stored whole blood also improves outcomes in trauma patients. Whole blood has the advantage of providing red cells, plasma, and platelets together in a single unit, which simplifies and speeds the process of resuscitation, particularly in austere environments. The Joint Trauma System, the Defense Committee on Trauma, and the Armed Services Blood Program endorse the following: (1) whole blood should be used to treat hemorrhagic shock; (2) low-titer group O whole blood is the resuscitation product of choice for the treatment of hemorrhagic shock for all casualties at all roles of care; (3) whole blood should be available within 30 min of casualty wounding, on all medical evacuation platforms, and at all resuscitation and surgical team locations; (4) when whole blood is not available, component therapy should be available within 30 min of casualty wounding; (5) all prehospital medical providers should be trained and logistically supported to screen donors, collect fresh whole blood from designated donors, transfuse blood products, recognize and treat transfusion reactions, and complete the minimum documentation requirements; (6) all deploying military personnel should undergo walking blood bank prescreen laboratory testing for transfusion transmitted disease immediately prior to deployment. Those who are blood group O should undergo anti-A/anti-B antibody titer testing., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Little is known regarding the effect of hemorrhagic shock on the diagnosis and treatment of tension pneumothorax (tPTX). Recently, the Tactical Combat Casualty Care guidelines included the 10-gauge angiocatheter (10-g AC) as an acceptable alternative to the 14-g AC. This study sought to compare these two devices for decompression of tPTX and rescue from tension-induced pulseless electric activity (tPEA) in the setting of a concomitant 30% estimated blood volume hemorrhage., Methods: Following a controlled hemorrhage, carbon dioxide was insufflated into the chest to induce either tPTX or tPEA. Tension pneumothorax was defined as a reduction in cardiac output by 50%, and tPEA was defined as a loss of arterial waveform with mean arterial pressure less than 20 mm Hg. The affected hemithorax was decompressed using a randomized 14-g AC or 10-g AC while a persistent air leak was maintained after decompression. Successful rescue from tPTX was defined as 80% recovery of baseline systolic blood pressure, while successful return of spontaneous circulation following tPEA was defined as a mean arterial pressure greater than 20 mm Hg. Primary outcome was success of device., Results: Eighty tPTX and 50 tPEA events were conducted in 38 adult Yorkshire swine. There were no significant differences in the baseline characteristics between animals or devices. In the tPTX model, the 10-g AC successfully rescued 90% of events, while 14-g AC rescued 80% of events (p = 0.350). In the tPEA model, the 10-g AC rescued 87% of events while the 14 AC rescued only 48% of events (p = 0.006)., Conclusion: The 10-g AC was vastly superior to the 14-g AC for return of spontaneous circulation following tPEA in the setting of 30% hemorrhage. These findings further support the importance of larger caliber devices that facilitate rapid recovery from tPTX, particularly in the setting of polytrauma., Level of Evidence: Therapeutic, level II.

Calcium electroporation is a novel anti-cancer treatment investigated in clinical trials. We explored cell sensitivity to calcium electroporation and electroporation with bleomycin, using viability assays at different time and temperature points, as well as heat calorimetry, lipidomics, and flow cytometry. Three cell lines: HT29 (colon cancer), MDA-MB231 (breast cancer), and HDF-n (normal fibroblasts) were investigated for; (a) cell survival dependent on time of addition of drug relative to electroporation (1.2 kV/cm, 8 pulses, 99 µs, 1 Hz), at different temperatures (37 °C, 27 °C, 17 °C); (b) heat capacity profiles obtained by differential scanning calorimetry without added calcium; (c) lipid composition by mass spectrometry; (d) phosphatidylserine in the plasma membrane outer leaflet using flow cytometry. Temperature as well as time of drug administration affected treatment efficacy in HT29 and HDF-n cells, but not MDA-MB231 cells. Interestingly the HT29 cell line displayed a higher phase transition temperature (approximately 20 °C) versus 14 °C (HDF-n) and 15 °C (MDA-MB231). Furthermore the HT29 cell membranes had a higher ratio of ethers to esters, and a higher expression of phosphatidylserine in the outer leaflet. In conclusion, lipid composition and heat capacity of the membrane might influence permeabilisation of cells and thereby the effect of calcium electroporation and electrochemotherapy.

Background: Objective parameters predicting futility of care in severely injured pediatric patients are lacking. Although futility of care has been investigated in a limited number of studies in trauma patients, none of these studies achieves a 100% success rate in a large cohort of pediatric patients. The purpose of the current study was to identify extreme laboratory values that could be used to predict 100% mortality in severely injured children., Study Design: We evaluated a registry-based, historical cohort of all severely injured children (Level I trauma, younger than 16 years old) who were not dead on arrival between January 2010 and December 2016 from a single Level I trauma center. Extreme arrival laboratory data were evaluated both alone and in conjunction with traumatic brain injury., Results: There were 1,292 patients who met inclusion criteria, of which 1,169 (90.5%) survived and 123 (9.5%) died. Those who died were significantly younger, with higher head Abbreviated Injury Scale scores and overall Injury Severity Scores. Single extreme laboratory values were identified that predicted mortality perfectly (100% positive predictive value): international normalized ratio ≥3.0, pH ≤6.95, base excess ≤ -22, platelet count ≤30,000, hemoglobin ≤5.0 g/dL, rapid thromboelastography ≤30 mm, and rapid thromboelastography lysis at 30 minutes ≥50%. When 2 laboratory values or the presence of traumatic brain injury were added, lower thresholds for futility were noted., Conclusions: Extreme admission laboratory values are capable of predicting 100% mortality and futility of additional care in severely injured children with a high level of accuracy. Validation of these single-center findings is warranted and, if supported, should initiate a discussion within the pediatric trauma community about application and cessation of resuscitation efforts to optimize resource use., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

We demonstrate that conditioning of mammalian cells by electroporation with nanosecond pulsed electric field (nsPEF) facilitates their response to the next nsPEF treatment. The experiments were designed to unambiguously separate the electroporation-induced sensitization and desensitization effects. Electroporation was achieved by bursts of 300-ns, 9 kV/cm pulses (50 Hz, n = 3-100) and quantified by propidium dye uptake within 11 min after the nsPEF exposure. We observed either sensitization to nsPEF or no change (when the conditioning was either too weak or too intense, or when the wait time after conditioning was too short). Within studied limits, conditioning never caused desensitization. With settings optimal for sensitization, the second nsPEF treatment became 2.5 times (25 °C) or even 6 times (37 °C) more effective than the same nsPEF treatment delivered without conditioning. The minimum wait time required for sensitization development was 30 s, with still longer delays increasing the effect. We show that the delayed hypersensitivity was not mediated by either cell swelling or oxidative effect of the conditioning treatment; biological mechanisms underlying the delayed electrosensitization remain to be elucidated. Optimizing nsPEF delivery protocols to induce sensitization can reduce the dose and adverse side effects of diverse medical treatments which require multiple pulse applications.

Electroporation by nanosecond electric pulses (nsEP) is an emerging modality for tumor ablation. Here we show the efficient induction of apoptosis even by a non-toxic nsEP exposure when it is followed by a 30-min chilling on ice. This chilling itself had no impact on the survival of U-937 or HPAF-II cells, but caused more than 75% lethality in nsEP-treated cells (300 ns, 1.8-7 kV/cm, 50-700 pulses). The cell death was largely delayed by 5-23 hr and was accompanied by a 5-fold activation of caspase 3/7 (compared to nsEP without chilling) and more than 60% cleavage of poly-ADP ribose polymerase (compared to less than 5% in controls or after nsEP or chilling applied separately). When nsEP caused a transient permeabilization of 83% of cells to propidium iodide, cells placed at 37 °C resealed in 10 min, whereas 60% of cells placed on ice remained propidium-permeable even in 30 min. The delayed membrane resealing caused cell swelling, which could be blocked by an isosmotic addition of a pore-impermeable solute (sucrose). However, the block of swelling did not prevent the delayed cell death by apoptosis. The potent enhancement of nsEP cytotoxicity by subsequent non-damaging chilling may find applications in tumor ablation therapies.

Adolescents are in a transitional phase of life characterized by major physical, emotional, and psychological challenges. Living with ulcerative colitis is experienced as a reduction of their life quality. Initial treatment of ulcerative colitis is medical, but surgery may be necessary when medical treatment ceases to have an effect. No research-based studies of adolescents' experience of the hospital period after surgery for ulcerative colitis exist. The objective of the study was to identify and describe adolescents' lived experiences while hospitalized after surgery for ulcerative colitis. This qualitative study was based on interviews with eight adolescents. Analysis and interpretation were based on a hermeneutic interpretation of meaning. Three themes were identified: Body: Out of order; Seen and understood; and Where are all the others? The adolescents experience a postoperative period characterized by physical and mental impairment. Being mentally unprepared for such challenges, they shun communication and interaction. The findings demonstrate the importance of individualized nursing care on the basis of the adolescent's age, maturity, and individual needs. Further study of adolescent patients' hospital stay, focusing on the implications of being young and ill at the same time, is needed.

The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21°C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent addition of venom and antivenoms, neutralization depended on the time interval between venom addition and antivenom application. When taipoxin was incubated for 5, 10 or 20min at 21°C, and antivenom added and temperature increased to 37°C, neutralization was achieved only when the toxin was incubated for 5 or 10min. The neutralization by the two antivenoms in an in vivo model showed that both whole IgG and F(ab')2 antivenoms were effective in neutralizing lethality. Our findings highlight the very rapid action of taipan venom at the nerve terminal, and the poor capacity of antivenoms to revert neurotoxicity as the time interval between venom or taipoxin application and antivenom addition increased. Additionally the disparity between molecular masses of the active substances of the two antivenoms did not result in differences in neutralization., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Antivenoms manufactured by bioCSL Limited (Australia) and Instituto Clodomiro Picado (Costa Rica) against the venom of the taipan snakes (Oxyuranus scutellatus) from Australia and Papua New Guinea (PNG), respectively, were compared using antivenomics, an analytical approach that combines proteomics with immunoaffinity chromatography. Both antivenoms recognized all venom proteins present in venom from PNG O. scutellatus, although a pattern of partial recognition was observed for some components. In the case of the Australian O. scutellatus venom, both antivenoms immunorecognized the majority of the components, but the CSL antivenom showed a stronger pattern of immunoreactivity, which was revealed by the percentage of retained proteins in the immunoaffinity column. Antivenoms interacted with taipoxin in surface plasmon resonance. These observations on antivenomics agree with previous neutralization studies., (© The American Society of Tropical Medicine and Hygiene.)

The venom proteomes of populations of the highly venomous taipan snake, Oxyuranus scutellatus, from Australia and Papua New Guinea (PNG), were characterized by reverse-phase HPLC fractionation, followed by analysis of chromatographic fractions by SDS-PAGE, N-terminal sequencing, MALDI-TOF mass fingerprinting, and collision-induced dissociation tandem mass spectrometry of tryptic peptides. Proteins belonging to the following seven protein families were identified in the two venoms: phospholipase A(2) (PLA(2)), Kunitz-type inhibitor, metalloproteinase (SVMP), three-finger toxin (3FTx), serine proteinase, cysteine-rich secretory proteins (CRISP), and coagulation factor V-like protein. In addition, C-type lectin/lectin-like protein and venom natriuretic peptide were identified in the venom of specimens from PNG. PLA(2)s comprised more than 65% of the venoms of these two populations. Antivenoms generated against the venoms of these populations showed a pattern of cross-neutralization, corroborating the immunological kinship of these venoms. Toxicity experiments performed in mice suggest that, at low venom doses, neurotoxicity leading to respiratory paralysis represents the predominant mechanism of prey immobilization and death. However, at high doses, such as those injected in natural bites, intravascular thrombosis due to the action of the prothrombin activator may constitute a potent and very rapid mechanism for killing prey., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Gas to liquids (GTL) products have the potential to replace petroleum-derived products, but the efficacy with which any sustainability goals can be achieved is dependent on the lifecycle impacts of the GTL pathway. Life cycle assessment (LCA) is an internationally established tool (with GHG emissions as a subset) to estimate these impacts. Although the International Standard Organization's ISO 14040 standard advocates the system boundary expansion method (also known as the "displacement method" or the "substitution method") for life-cycle analyses, application of this method for the GTL pathway has been limited until now because of the difficulty in quantifying potential products to be displaced by GTL coproducts. In this paper, we use LCA methodology to establish the most comprehensive GHG emissions evaluation to date of the GTL pathway. The influence of coproduct credit methods on the GTL GHG emissions results using substitution methodology is estimated to afford the Well-to-Wheels (WTW) greenhouse gas (GHG) intensity of GTL Diesel. These results are compared to results using energy-based allocation methods of reference GTL diesel and petroleum-diesel pathways. When substitution methodology is used, the resulting WTW GHG emissions of the GTL pathway are lower than petroleum diesel references. In terms of net GHGs, an interesting way to further reduce GHG emissions is to blend GTL diesel in refineries with heavy crudes that require severe hydrotreating, such as Venezuelan heavy crude oil or bitumen derived from Canadian oil sands and in jurisdictions with tight aromatic specifications for diesel, such as California. These results highlight the limitation of using the energy allocation approach for situations where coproduct GHG emissions reductions are downstream from the production phase.

The development of snake antivenoms more than a century ago should have heralded effective treatment of the scourge of snakebite envenoming in impoverished, mostly rural populations around the world. That snakebite still exists today, as a widely untreated illness that maims, kills and terrifies men, women and children in vulnerable communities, is a cruel anachronism. Antivenom can be an effective, safe and affordable treatment for snakebites, but apathy, inaction and the politicisation of public health have marginalised both the problem (making snakebite arguably the most neglected of all neglected tropical diseases) and its solution. For lack of any coordinated approach, provision of antivenoms has been pushed off the public health agenda, leading to an incongruous decline in demand for these crucial antidotes, excused and fed by new priorities, an absence of epidemiological data, and a poor regulatory framework. These factors facilitated the infiltration of poor quality products that degrade user confidence and undermine legitimate producers. The result is that tens of thousands are denied an essential life-saving medicine, allowing a toll of human suffering that is a summation of many individual catastrophes. No strategy has been developed to address this problem and to overcome the intransigence and inaction responsible for the global tragedy of snakebite. Attempts to engage with the broader public health community through the World Health Organisation (WHO), GAVI, and other agencies have failed. Consequently, the toxinology community has taken on a leadership role in a new approach, the Global Snakebite Initiative, which seeks to mobilise the resources, skills and experience of scientists and clinicians for whom venoms, toxins, antivenoms, snakes and snakebites are already fields of interest. Proteomics is one such discipline, which has embraced the potential of using venoms in bio-discovery and systems biology. The fields of venomics and antivenomics have recently evolved from this discipline, offering fresh hope for the victims of snakebites by providing an exciting insight into the complexities, nature, fundamental properties and significance of venom constituents. Such a rational approach brings with it the potential to design new immunising mixtures from which to raise potent antivenoms with wider therapeutic ranges. This addresses a major practical limitation in antivenom use recognised since the beginning of the 20th century: the restriction of therapeutic effectiveness to the specific venom immunogen used in production. Antivenomic techniques enable the interactions between venoms and antivenoms to be examined in detail, and if combined with functional assays of specific activity and followed up by clinical trials of effectiveness and safety, can be powerful tools with which to evaluate the suitability of current and new antivenoms for meeting urgent regional needs. We propose two mechanisms through which the Global Snakebite Initiative might seek to end the antivenom drought in Africa and Asia: first by establishing a multidisciplinary, multicentre, international collaboration to evaluate currently available antivenoms against the venoms of medically important snakes from specific nations in Africa and Asia using a combination of proteomic, antivenomic and WHO-endorsed preclinical assessment protocols, to provide a validated evidence base for either recommending or rejecting individual products; and secondly by bringing the power of proteomics to bear on the design of new immunising mixtures to raise Pan-African and Pan-Asian polyvalent antivenoms of improved potency and quality. These products will be subject to rigorous clinical assessment. We propose radically to change the basis upon which antivenoms are produced and supplied for the developing world. Donor funding and strategic public health alliances will be sought to make it possible not only to sustain the financial viability of antivenom production partnerships, but also to ensure that patients are relieved of the costs of antivenom so that poverty is no longer a barrier to the treatment of this important, but grossly neglected public health emergency., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Snake bite is a common medical emergency in Papua New Guinea (PNG). The taipan, Oxyuranus scutellatus, inflicts a large number of bites that, in the absence of antivenom therapy, result in high mortality. Parenteral administration of antivenoms manufactured in Australia is the current treatment of choice for these envenomings. However, the price of these products is high and has increased over the last 25 years; consequently the country can no longer afford all the antivenom it needs. This situation prompted an international collaborative project aimed at generating a new, low-cost antivenom against O. scutellatus for PNG., Methodology/principal Findings: A new monospecific equine whole IgG antivenom, obtained by caprylic acid fractionation of plasma, was prepared by immunising horses with the venom of O. scutellatus from PNG. This antivenom was compared with the currently used F(ab')(2) monospecific taipan antivenom manufactured by CSL Limited, Australia. The comparison included physicochemical properties and the preclinical assessment of the neutralisation of lethal neurotoxicity and the myotoxic, coagulant and phospholipase A(2) activities of the venom of O. scutellatus from PNG. The F(ab')(2) antivenom had a higher protein concentration than whole IgG antivenom. Both antivenoms effectively neutralised, and had similar potency, against the lethal neurotoxic effect (both by intraperitoneal and intravenous routes of injection), myotoxicity, and phospholipase A(2) activity of O. scutellatus venom. However, the whole IgG antivenom showed a higher potency than the F(ab')(2) antivenom in the neutralisation of the coagulant activity of O. scutellatus venom from PNG., Conclusions/significance: The new whole IgG taipan antivenom described in this study compares favourably with the currently used F(ab')(2) antivenom, both in terms of physicochemical characteristics and neutralising potency. Therefore, it should be considered as a promising low-cost candidate for the treatment of envenomings by O. scutellatus in PNG, and is ready to be tested in clinical trials.

A sandwich hybridization assay (SHA) was developed to detect 16S rRNAs indicative of phylogenetically distinct groups of marine bacterioplankton in a 96-well plate format as well as low-density arrays printed on a membrane support. The arrays were used in a field-deployable instrument, the Environmental Sample Processor (ESP). The SHA employs a chaotropic buffer for both cell homogenization and hybridization, thus target sequences are captured directly from crude homogenates. Capture probes for seven of nine different bacterioplankton clades examined reacted specifically when challenged with target and non-target 16S rRNAs derived from in vitro transcribed 16S rRNA genes cloned from natural samples. Detection limits were between 0.10-1.98 and 4.43- 12.54 fmole ml(-1) homogenate for the 96-well plate and array SHA respectively. Arrays printed with five of the bacterioplankton-specific capture probes were deployed on the ESP in Monterey Bay, CA, twice in 2006 for a total of 25 days and also utilized in a laboratory time series study. Groups detected included marine alphaproteobacteria, SAR11, marine cyanobacteria, marine group I crenarchaea, and marine group II euryarchaea. To our knowledge this represents the first report of remote in situ DNA probe-based detection of marine bacterioplankton.

Objective: To examine antivenom use, premedication, early adverse reactions and patient outcomes after snake bite in rural Papua New Guinea., Design: Retrospective chart analysis of all admissions for snake bite with documented antivenom use at 11 rural health facilities from January 1994 to June 2004. No formal protocol was followed and there was no attempt at randomisation or blinding of prophylaxis., Results: Antivenom use was documented in 136/1881 (7.2%) snake bite admissions and most (121/136: 88.9%) received a single vial. CSL Polyvalent antivenom was administered to 112/136 (82.4%). One hundred and eleven patients (81.6%) happened to have been given premedication with adrenaline and/or promethazine and/or hydrocortisone. Early adverse reactions were reported in 25 patients (18.4%) including 23 treated with polyvalent antivenom. Intravenous test doses of antivenom were given to 32 patients, none of whom had a positive test result. Subsequent adverse reactions occurred in 9 of these 32 (28.1%) patients. One death may have been attributable to anaphylaxis after polyvalent antivenom. Reaction rates were significantly (p < or = 0.005) lower in adrenaline premedicated patients (7.7%) compared to patients premedicated without adrenaline (28.3%) and unpremedicated patients (28.0%). Adrenaline premedication caused no detectable changes in vital signs. The case fatality rate was 9.6% (13/136 patients)., Conclusions: Polyvalent antivenom is the main treatment for envenomation in rural health centres, and early adverse reactions are common. Adrenaline premedication appears to significantly reduce acute adverse reaction rates. Premedication with promethazine and/or hydrocortisone without adrenaline did not reduce early adverse reactions.

We report a novel one-pot two-step synthesis of a variety of S-alkyl thiocarbamates. This method offers a two-directional approach making use of trichloroacetyl chloride, requires no complex starting material, incorporates a variety of substituents, and proceeds in high yields.

The effect of long term steroid treatment on coagulation, intraosseous pressure (IOP), femoral head (FH) blood flow, and histology in the normal organism was investigated in this study in growing pigs. From 24 growing female Danish Landrace pigs from 12 litters, 12 animals daily received 100 mg methylprednisolone orally for three months. Their 12 sister pigs served as controls without steroid treatment. Prothrombin time, activated partial thromboplastin time (aPTT), fibrinogen, and antithrombin III levels were recorded in jugular venous blood. Blood flow of the hip regions was measured by means of the radioactive microsphere technique. Metaphyseal and epiphyseal IOP of the left or right proximal femur were measured. Histomorphometry of the left or right FH epiphysis was performed. Major growth inhibition was found in the corticosteroid (CS) treated group. In CS pigs, aPTT was shortened to 50% compared to control pigs. Plasma fibrinogen was higher in the CS animals. Total FH blood flow was not different while regional blood flow in the cranial subregion of the FH epiphysis was higher in the CS group. Metaphyseal and epiphyseal IOP of the proximal femur were not different in the CS animals. Histomorphometrically, cancellous bone volume (23 +/- 1% vs. 34 +/- 2%; p < 0.001) and bone turnover (10 +/- 2% vs. 55 +/- 8%; p < 0.001) of the FH epiphysis was lowerin the CS than in the control group. The FH epiphysis of the CS animals invariably showed an irregular cartilage-bone interface with cartilaginous projections into the subchondral bone mainly in its cranial part. In normal growing pigs, long term high dose CS treatment has induced a hypercoagulable state of plasma via the intrinsic pathway of coagulation, cartilaginous projections into FH subchondral bone, FH osteopenia, and reduced bone turnover. Long-term steroid treatment did not produce FH necrosis or FH IOP alterations in the immature pig model.

Study Design: Bone mineral density and regional blood flow were measured in pigs during long-term methylprednisolone treatment., Objectives: To investigate possible changes in bone mineral density and vertebral blood flow during long-term glucocorticoid treatment., Summary of Background Data: Steroid-induced vertebral osteonecrosis preferentially involves endplates and adjacent cancellous bone. The precise etiology of vertebral osteonecrosis during long-term glucocorticoid treatment is unknown., Methods: Twenty-four 10-week-old female Danish landrace sister pigs from 12 litters were treated in two groups. Twelve animals received oral methylprednisolone for 3 months at a daily dose of 100 mg. The 12 sister pigs received no steroid treatment and served as controls. Regional blood blow was measured by means of microspheres in predefined regions of the C6, T11, and L6 vertebrae. In vitro DEXA scanning of the L2-L4 vertebra was performed to assess bone mineral density., Results: Vertebral cancellous bone and endplate regional blood flow were decreased in the C6 and L6 vertebrae among corticosteroid-treated pigs compared with that of controls.- Width-adjusted lumbar vertebral bone mineral density (g/cm3) was unchanged, whereas projectional lumbar vertebral bone mineral density (g/cm2) was decreased in corticosteroid-treated pigs., Conclusions: Long-term methylprednisolone treatment decreases vertebral bone blood flow mainly in cancellous bone and endplates. This may be an important factor in the pathogenesis of osteonecrosis secondary to glucocorticoid treatment. Lumbar vertebral bone mineral density was unchanged in growing pigs on long-term glucocorticoid treatment when expressed as volumetric bone density. The effect of glucocorticoid treatment on vertebral bone mineral density appears to depend on whether it is expressed as projectional (g/cm2) or volumetric bone mineral density (g/cm3). Vertebral and longbone growth was reduced during methylprednisolone treatment.