Total spinal anaesthesia following obstetric neuraxial blockade: a narrative review.

BACKGROUND: Total spinal anaesthesia (TSA) is an emergency caused by high neuraxial blockade. It is a recognised complication of all neuraxial techniques in obstetric anaesthesia. Its incidence and outcomes have not been evaluated. There is compelling evidence that TSA continues to be a problem in contemporary practice, having the capacity to cause significant morbidity and mortality if not recognised early and promptly treated. This review based on a literature search aims to clarify the epidemiology of TSA, summarise its pathophysiology, and identify risk factors and effective treatments. METHODS: We performed a literature search using PubMed, Web of Science and Google Scholar databases using specified search terms for materials published using search terms. For each case, the type of block, the difficulty of the procedure, the dose of local anaesthetic, positivity of aspiration before and after the event, maternal outcome, Apgar score, onset of symptoms, cardiorespiratory and neurological manifestations, cardiorespiratory support employed, admission to an intensive care unit, cardiac arrest events and duration of mechanical ventilation were extracted. RESULTS: A total of 605 cases were identified, of which 51 were sufficiently detailed for analysis. Although TSA is described after all neuraxial techniques, spinal after epidural was a particular concern in recent reports. Respiratory distress was universal but apnoea was not. The onset of apnoea was variable, ranging from 1 to 180 min. Hypotension was not invariable and occurred in approximately half of cases. Multiple fatalities and neurological injuries were reported, often in under-resourced areas when providers were not skilled in airway management or when recognition and intervention were delayed. In the most recent reports good outcomes were achieved when effective treatments were rapidly provided. CONCLUSIONS: The available literature confirms that TSA remains an active clinical problem and that with prompt recognition and treatment good outcomes can be achieved. This requires anticipation and preparedness in all clinical areas where neuraxial techniques are performed.

Building Back Better: Going Big with Emancipatory Sciences.

This commentary argues that precarity and inequity across the life course and aging has accelerated via the COVID-19 pandemic. President Biden's vaccination efforts, $1.9 trillion American Rescue Plan Act, and Build Back Better framework reflect a paradigm shift to restore faith and trust in government that boldly confronts entrenched austerity ideologues. We offer emancipatory sciences as a conceptual framework to analyze and promote social structural change and epic theory development. Emancipatory sciences aim to advance knowledge and the realization of dignity, access, equity, respect, healing, social justice, and social change through individual and collective agency and social institutions. Epic theory development moves beyond isolated incidents as single events and, instead, grasps and advances theory through attempts to change the world itself by demanding attention to inequality, power, and action. Gerontology with an emancipatory science lens offers a framework and vocabulary to understand the individual and collective consequences of the institutional and policy forces that shape aging and generations within and across the life course. It locates an ethical and moral philosophy engaged in the Biden Administration's approach, which proposes redistributing - from bottom-up - material and symbolic resources via family, public, community, and environmental benefits.

Biopsychosocial sequelae and recovery trajectories from whiplash injury following a motor vehicle collision.

BACKGROUND CONTEXT: Five out of 10 injured in a motor vehicle collision (MVC) will develop persistent pain and disability. It is unclear if prolonged symptoms are related to peritraumatic pain/disability, psychological distress, muscle fat, lower extremity weakness. PURPOSE: To test if widespread muscle fat infiltration (MFI) was (1) unique to those with poor recovery, (2) present in the peritraumatic stage, (3) related to known risk factors. STUDY DESIGN/SETTING: A cohort study, single-center academic hospital. PATIENT SAMPLES: A total of 97 men and women (age 18-65) presenting to an urban academic emergency medicine department following MVC, but not requiring inpatient hospitalization. PRIMARY OUTCOME MEASURE: Neck disability at 12-months. METHODS: Participants underwent magnetic resonance imaging (MRI) to quantify neck and lower extremity MFI, completed questionnaires on pain/disability and psychological distress (< 1-week, 2-weeks, 3-, and 12-months) and underwent maximum volitional torque testing of their lower extremities (2-weeks, 3-, and 12-months). Percentage score on the Neck Disability Index at 12-months was used for a model of (1) Recovered (0%-8%), (2) Mild (10%-28%), and (3) Moderate/Severe (≥ 30%). This model was adjusted for BMI and age. RESULTS: Significant differences for neck MFI were revealed, with the Recovered group having significantly lower neck MFI than the Mild and Moderate/Severe groups at all time points. The Mild group had significantly more leg MFI at 12-months (p=.02) than the Recovered group. There were no other significant differences at any other time point. Lower extremity torques revealed no group differences. The Traumatic Injury Distress Scale (TIDS) and MFI of the neck at 1-week postinjury significantly predicted NDI score at 12-months. CONCLUSIONS: Higher neck MFI and distress may represent a risk factor though it is unclear whether this is a pre-existing phenotype or result of the trauma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02157038.

Affinity of anti-spike antibodies to three major SARS-CoV-2 variants in recipients of three major vaccines.

Background: Measuring anti-viral antibody affinity in blood plasma or serum is a rational quantitative approach to assess humoral immune response and acquired protection. Three common vaccines against SARS-CoV-2-Comirnaty developed by Pfizer/BioNTech, Spikevax developed by Moderna/NIAID, and Jcovden (previously Janssen COVID-19 Vaccine) developed by Johnson & Johnson/Janssen (J&J)-induce antibodies to a variety of immunogenic epitopes including the epitopes located in the ACE2 receptor-binding domain (RBD) of the spike protein. Blocking RBD with antibodies interferes with the binding of the virus to ACE2 thus protecting against infection. Methods: We perform measurements in the serum of the recipients of Pfizer, Moderna, and J&J vaccines, and we compare the apparent affinities of vaccine-induced antibodies against the RBD of the ancestral SARS-CoV-2 virus and the Delta and Omicron variants. We use our recently published method to determine the apparent affinity of anti-spike protein antibodies directly in human serum. This involves probing antibody-antigen equilibria with a small number of antigen-coated magnetic microparticles and imaging them on a fluorescence microscope. Results: Recipients of two-dose Pfizer and Moderna vaccines, as well as recipients of the single-dose J&J vaccine, develop high-affinity antibodies toward RBD derived from ancestral SARS-CoV-2. Affinities of these antibodies to Delta-RBD are approximately 10 times weaker, and even more drastically reduced (∼1000-fold) toward Omicron-RBD. Conclusions: Vaccine-induced antibodies against ancestral SARS-CoV-2 RBD demonstrate ~10-fold and ~1000-fold weaker affinities toward Delta- and Omicron-RBD, respectively. Our approach offers a direct means for evaluating vaccine-induced adaptive immunity and can be helpful in designing or updating vaccines.

Utilizing evidence-based guidelines to develop a language barriers simulation.

BACKGROUND: The United States population is becoming increasingly diverse. Despite this trend, diversity in the nursing profession lags. In order to provide patient-centered care, students must learn the nuances of providing culturally competent care. There are many ways to assess the impact of culture on healthcare behaviors and norms, and can include, but are not limited to, ethnicity, sexual orientation, or religious preference. Clinical experiences offer inconsistent opportunities for students to interact with potentially diverse patients. OBJECTIVE: The aim of this project was to develop a simulation that built upon curricular objectives and evidence-based guidelines for healthcare providers communicating across language barriers. FINDINGS: Regulations and evidence-based guidelines describe how to provide quality patient-centered care to diverse groups of patients. These guidelines can be adapted at the clinician and systems level to facilitate culturally sensitive and linguistically appropriate services to patients. These guidelines were applied in an educational setting, and combined with best practices in simulation, to enhance undergraduate nursing students' experience in caring for diverse patients. CONCLUSION: The use of simulation can be optimized when based on evidence-based guidelines encountered in clinical care.

Radio- and nano-chemistry of aqueous Ga(iii) ions anchored onto graphene oxide-modified complexes.

The gallium-68 radiolabelling of new functional graphene oxide composites is reported herein along with kinetic stability investigations of the radio-nanohybrids under different environments and insights into their surface characteristics by SEM and XPS. The present work highlights the potential of graphene oxides as nanocarriers for small molecules such as bis(thiosemicarbazonato) complexes to act as multifunctional platforms for rapid and effective radioimaging agent incorporation.

Reliability and validity of self-reported questionnaires to measure pain and disability in adults with neck pain and its associated disorders: part 3-a systematic review from the CADRE Collaboration.

PURPOSE: To determine the reliability and validity of self-reported questionnaires to measure pain and disability in adults with grades I-IV neck pain and its associated disorders (NAD). METHODS: We updated the systematic review of the 2000-2010 Bone and Joint Decade Task Force on Neck Pain and its Associated Disorders and systematically searched databases from 2005 to 2017. Independent reviewers screened and critically appraised studies using standardized tools. Evidence from low-risk-of-bias studies was synthesized according to best evidence synthesis principles. Validity studies were ranked according to the Sackett and Haynes classification. RESULTS: We screened 2823 articles, and 26 were eligible for critical appraisal; 18 were low risk of bias. Preliminary evidence suggests that the Neck Disability Index (original and short versions), Whiplash Disability Questionnaire, Neck Pain Driving Index, and ProFitMap-Neck may be valid and reliable to measure disability in patients with NAD. We found preliminary evidence for the validity and reliability of pain measurements including the Body Pain Diagram, Visual Analogue Scale, the Numeric Rating Scale and the Pain-DETECT Questionnaire. CONCLUSION: The evidence supporting the validity and reliability of instruments used to measure pain and disability is preliminary. Further validity studies are needed to confirm the clinical utility of self-reported questionnaires to assess pain and disability in patients with NAD. These slides can be retrieved under Electronic Supplementary Material.

The origin and stability of nanostructural hierarchy in crystalline solids.

The structural hierarchy exhibited by materials on more than one length scale can play a major part in determining bulk material properties. Understanding the hierarchical structure can lead to new materials with physical properties tailored for specific applications. We have used a combined experimental and phase-field modeling approach to explore such a hierarchical structure at nanoscale for enhanced coarsening resistance of ordered γ' precipitates in an experimental, multicomponent, high-refractory nickel-base superalloy. The hierarchical microstructure formed experimentally in this alloy is composed of a γ matrix with γ' precipitates that contain embedded, spherical γ precipitates, which do not directionally coarsen during high-temperature annealing but do delay coarsening of the larger γ' precipitates. Chemical mapping via atom probe tomography suggests that the supersaturation of Co, Ru, and Re in the γ' phase is the driving force for the phase separation, leading to the formation of this hierarchical microstructure. Representative phase-field modeling highlights the importance of larger γ' precipitates to promote stability of the embedded γ phase and to delay coarsening of the encompassing γ' precipitates. Our results suggest that the hierarchical material design has the potential to influence the high-temperature stability of precipitate strengthened metallic materials.

Towards an MMP-2-activated molecular agent for cancer imaging.

Matrix metalloproteinases (MMPs) have been identified as biomarkers for cancer, offering prognostic potential; however, non-invasive detection protocols are currently lacking. Herein, we describe the synthesis of a DOTA-containing peptide sequence that can be radiolabelled easily with 68Gallium or can be incorporated with gadolinium for possible MRI applications with clear selectivity for MMP-2 over other members of the MMP family, giving MMP-2 selective cleavage of the labelled peptides.

Reliability and validity of clinical tests to assess the anatomical integrity of the cervical spine in adults with neck pain and its associated disorders: Part 1-A systematic review from the Cervical Assessment and Diagnosis Research Evaluation (CADRE) Collaboration.

OBJECTIVE: To determine the reliability and validity of clinical tests to assess the anatomical integrity of the cervical spine in adults with neck pain and its associated disorders. METHODS: We updated the systematic review of the 2000-2010 Bone and Joint Decade Task Force on Neck Pain and its Associated Disorders. We also searched the literature to identify studies on the reliability and validity of Doppler velocimetry for the evaluation of cervical arteries. Two independent reviewers screened and critically appraised studies. We conducted a best evidence synthesis of low risk of bias studies and ranked the phases of investigations using the classification proposed by Sackett and Haynes. RESULTS: We screened 9022 articles and critically appraised 8 studies; all 8 studies had low risk of bias (three reliability and five validity Phase II-III studies). Preliminary evidence suggests that the extension-rotation test may be reliable and has adequate validity to rule out pain arising from facet joints. The evidence suggests variable reliability and preliminary validity for the evaluation of cervical radiculopathy including neurological examination (manual motor testing, dermatomal sensory testing, deep tendon reflexes, and pathological reflex testing), Spurling's and the upper limb neurodynamic tests. No evidence was found for doppler velocimetry. CONCLUSIONS: Little evidence exists to support the use of clinical tests to evaluate the anatomical integrity of the cervical spine in adults with neck pain and its associated disorders. We found preliminary evidence to support the use of the extension-rotation test, neurological examination, Spurling's and the upper limb neurodynamic tests.

Antibiotic-Induced Rash in Patients With Infectious Mononucleosis.

OBJECTIVE: To provide an extensive review of case reports, epidemiological data, and the underlying mechanism of antibiotic-induced skin rash in patients with concurrent infectious mononucleosis (IM). DATA SOURCES: A MEDLINE literature search inclusive of the dates 1946 to June 2016 was performed using the search terms anti-bacterial agents and infectious mononucleosis. EMBASE (1980 to June 2016) was searched using the terms mononucleosis and antibiotic agent and drug eruption. References of all relevant articles were reviewed for additional citations and information. STUDY SELECTION AND DATA EXTRACTION: We selected English-language, primary literature, review articles, and mechanistic articles that addressed antibiotic-induced skin rash in patients with concurrent IM. We assessed all case reports available for causality utilizing a modified Naranjo nomogram specifically designed for this subject. We assembled the available epidemiological data into tables to identify trends in incidence rates over the years. DATA SYNTHESIS: We identified 17 case reports of antibiotic-associated rash in patients with IM. The median Naranjo score was 6 (range = 1 to 8). The top 3 reported drugs were ampicillin, azithromycin, and amoxicillin. Incidence of this adverse effect was higher in the 1960s (55.6%, 45%, and 33%) than in 2013 (33% and 15%). The mechanism most commonly proposed is a transient virus-mediated immune alteration that sets the stage for loss of antigenic tolerance and the development of a reversible, delayed-type hypersensitivity reaction to the antibiotic. CONCLUSION: A reassessment of the long-held belief of the high incidence (80%-100%) of antibiotic-induced skin rash in patients with IM seems prudent. Additional studies will be necessary to clarify this issue.

Clinical practice guidelines for the noninvasive management of low back pain: A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

We conducted a systematic review of guidelines on the management of low back pain (LBP) to assess their methodological quality and guide care. We synthesized guidelines on the management of LBP published from 2005 to 2014 following best evidence synthesis principles. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane, DARE, National Health Services Economic Evaluation Database, Health Technology Assessment Database, Index to Chiropractic Literature and grey literature. Independent reviewers critically appraised eligible guidelines using AGREE II criteria. We screened 2504 citations; 13 guidelines were eligible for critical appraisal, and 10 had a low risk of bias. According to high-quality guidelines: (1) all patients with acute or chronic LBP should receive education, reassurance and instruction on self-management options; (2) patients with acute LBP should be encouraged to return to activity and may benefit from paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), or spinal manipulation; (3) the management of chronic LBP may include exercise, paracetamol or NSAIDs, manual therapy, acupuncture, and multimodal rehabilitation (combined physical and psychological treatment); and (4) patients with lumbar disc herniation with radiculopathy may benefit from spinal manipulation. Ten guidelines were of high methodological quality, but updating and some methodological improvements are needed. Overall, most guidelines target nonspecific LBP and recommend education, staying active/exercise, manual therapy, and paracetamol or NSAIDs as first-line treatments. The recommendation to use paracetamol for acute LBP is challenged by recent evidence and needs to be revisited. SIGNIFICANCE: Most high-quality guidelines recommend education, staying active/exercise, manual therapy and paracetamol/NSAIDs as first-line treatments for LBP. Recommendation of paracetamol for acute LBP is challenged by recent evidence and needs updating.

Design, synthesis and initial characterisation of a radiolabelled [(18)F]pyrimidoindolone probe for detecting activated caspase-3/7.

Evasion of apoptosis is one of the six initially proposed hallmarks of cancer, and as such, a method to detect apoptosis in a tumour would be of considerable interest in both clinical trials of new cancer therapeutics, as well as for routine patient management. Activation of caspase-3/7 is a key biomarker of cellular apoptosis. Herein we describe the design, synthesis and initial characterisation of the first pyrimidoindolone compound for detection of caspase-3/7 activation using positron emission tomography.

Reaction of low-molecular-mass organoselenium compounds (and their sulphur analogues) with inflammation-associated oxidants.

Selenium is an essential trace element in mammals, with the majority specifically encoded as seleno-L-cysteine into a range of selenoproteins. Many of these proteins play a key role in modulating oxidative stress, via either direct detoxification of biological oxidants, or repair of oxidised residues. Both selenium- and sulphur-containing residues react readily with the wide range of oxidants (including hydrogen peroxide, radicals, singlet oxygen and hypochlorous, hypobromous, hypothiocyanous and peroxynitrous acids) that are produced during inflammation and have been implicated in the development of a range of inflammatory diseases. Whilst selenium has similar properties to sulphur, it typically exhibits greater reactivity with most oxidants, and there are considerable differences in the subsequent reactivity and ease of repair of the oxidised species that are formed. This review discusses the chemistry of low-molecular-mass organoselenium compounds (e.g. selenoethers, diselenides and selenols) with inflammatory oxidants, with a particular focus on the reaction kinetics and product studies, with the differences in reactivity between selenium and sulphur analogues described in the selected examples. These data provide insight into the therapeutic potential of low-molecular-mass selenium-containing compounds to modulate the activity of both radical and molecular oxidants and provide protection against inflammation-induced damage. Progress in their therapeutic development (including modulation of potential selenium toxicity by strategic design) is demonstrated by a brief summary of some recent studies where novel organoselenium compounds have been used as wound healing or radioprotection agents and in the prevention of cardiovascular disease.

Mn-salen catalysed benzylic C-H activation for the synthesis of aryl [(18)F]CF3-containing PET probes.

The development of a Mn-salen complex catalysed oxidative benzylic fluorination of non-activated C-H bonds using [(18)F]fluoride is described for installation of [(18)F]CHRF, [(18)F]CR2F and particularly [(18)F]CF3 containing groups in the presence of other functional groups.

A population-based, incidence cohort study of mid-back pain after traffic collisions: Factors associated with global recovery.

BACKGROUND: Traffic collisions often result in a wide range of symptoms included in the umbrella term whiplash-associated disorders. Mid-back pain (MBP) is one of these symptoms. The incidence and prognosis of different traffic injuries and their related conditions (e.g. neck pain, low back pain, depression or others) has been investigated previously; however, knowledge about traffic collision-related MBP is lacking. The study objectives were to describe the incidence, course of recovery and prognosis of MBP after traffic collisions, in terms of global self-reported recovery. METHODS: Longitudinal data from a population-based inception cohort of all traffic injuries occurring in Saskatchewan, Canada, during a 2-year period were used. Annual overall and age-sex-specific incidence rates were calculated, the course of recovery was described using the Kaplan-Meier technique, and associations between participant characteristics and time-to-self-reported recovery were explored in 3496 MBP cases using Cox proportional hazards models. RESULTS: The yearly incidence rate was 236 per 100,000 population during the study period, and was highest in women and in young persons. The median time-to-first reported recovery was 101 days (95% CI: 99-104) and about 23% were still not recovered after 1 year. Participant's expectation for recovery, general health, extent of severely affecting comorbidities and having experienced a previous traffic injury were some of the prognostic factors identified. CONCLUSIONS: These findings show that MBP is common after traffic collisions, may result in a long recovery process and that a range of biopsychosocial factors are associated with recovery.

Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells.

BACKGROUND: The sequence of the beta-subunit of human chorionic gonadotropin (hCGß) varies depending on whether hCGß is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCGß can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCGß encoded by type II genes (type II hCGß). METHODS: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCGß dosing immunoassays and sequencing of CGB genes were performed. RESULTS: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCGß derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and T24 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCGß. Placenta immunohistochemical studies confirmed that type II hCGß expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCGß in serum of patients with either nontrophoblastic cancers or fetal Down syndrome. CONCLUSION: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.