Cas12a2 elicits abortive infection through RNA-triggered destruction of dsDNA.

Bacterial abortive-infection systems limit the spread of foreign invaders by shutting down or killing infected cells before the invaders can replicate1,2. Several RNA-targeting CRISPR-Cas systems (that is, types III and VI) cause abortive-infection phenotypes by activating indiscriminate nucleases3-5. However, a CRISPR-mediated abortive mechanism that leverages indiscriminate DNase activity of an RNA-guided single-effector nuclease has yet to be observed. Here we report that RNA targeting by the type V single-effector nuclease Cas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA (dsDNA). After recognizing an RNA target with an activating protospacer-flanking sequence, Cas12a2 efficiently degrades single-stranded RNA (ssRNA), single-stranded DNA (ssDNA) and dsDNA. Within cells, the activation of Cas12a2 induces an SOS DNA-damage response and impairs growth, preventing the dissemination of the invader. Finally, we harnessed the collateral activity of Cas12a2 for direct RNA detection, demonstrating that Cas12a2 can be repurposed as an RNA-guided RNA-targeting tool. These findings expand the known defensive abilities of CRISPR-Cas systems and create additional opportunities for CRISPR technologies.

Rapid and Scalable Characterization of CRISPR Technologies Using an E. coli Cell-Free Transcription-Translation System.

CRISPR-Cas systems offer versatile technologies for genome engineering, yet their implementation has been outpaced by ongoing discoveries of new Cas nucleases and anti-CRISPR proteins. Here, we present the use of E. coli cell-free transcription-translation (TXTL) systems to vastly improve the speed and scalability of CRISPR characterization and validation. TXTL can express active CRISPR machinery from added plasmids and linear DNA, and TXTL can output quantitative dynamics of DNA cleavage and gene repression-all without protein purification or live cells. We used TXTL to measure the dynamics of DNA cleavage and gene repression for single- and multi-effector CRISPR nucleases, predict gene repression strength in E. coli, determine the specificities of 24 diverse anti-CRISPR proteins, and develop a fast and scalable screen for protospacer-adjacent motifs that was successfully applied to five uncharacterized Cpf1 nucleases. These examples underscore how TXTL can facilitate the characterization and application of CRISPR technologies across their many uses.

Exploring substance misuse in a prison in Wales: a cross-sectional analysis.

BACKGROUND: Since 2015, the risks of dying due to drug-related causes are higher in prison than in the general population, with opiates and psychoactive substances being the most common substances recorded on death certificates in prison. Many individuals use drugs before entering the prison environment, it is not clear which individuals continue to use drugs while in prison. This study is a first step towards identifying characteristics of those who use drugs in prison, while exploring substances commonly used. METHODS: This retrospective cross-sectional analysis was performed on 299 men (mean age 38 years [SD 11]) in a long-stay UK prison in South Wales who participated in a research study exploring cardiometabolic risk in prison, in which substance misuse was included as a risk variable. All men aged 25 years or older with no previous diagnosis of cardiometabolic illness were eligible to participate. Data were collected between Oct 7 and Oct 23, 2019. Participants were asked details about their substance use before and since entering the prison. Mental wellbeing was assessed using the short Warwick Edinburgh Mental Wellbeing Score and low mental wellbeing calculated as 1 SD below the population mean score. To examine associations between characteristics (age groups, mental wellbeing, exposure to prison environment) and drug use, we used binary logistic regression (adjusted for characteristics such as age group, mental wellbeing, and exposure to prison environment ). FINDINGS: Overall, 195 (65%) of 299 participants reported a history of drug use before entering prison. Since entering prison 49 (16%) participants reported using drugs including methadone, and 24 (8%) reported using drugs excluding methadone. The next leading substances used in prison were spice (11 [4%] participants) and cannabis (six [2%] participants). All those who used drugs in prison had a history of drug use. Individuals more likely to continue using drugs in prison were aged 39 years and younger (adjusted odds ratio [aOR] 4·72, 95% CI 1·88-11·89; p=0·0009), with reported low mental wellbeing (3·38, 1·54-7·41; p=0·002), and had spent collectively more than 2·5 years in the prison environment (4·77, 2·09-10·91; p=0·0002). INTERPRETATION: This study, from a limited sample, describes the characteristics of those who use drugs in prison. Harm reduction interventions targeted to these individuals could reduce the risk of prison drug-related deaths. These findings should be interpreted with some caution, as this is a single site and may not reflect the wider UK prison environment. FUNDING: Public Health Wales.

A 3-year review of deaths in people under community justice supervision in Wales: a cross-sectional analysis.

BACKGROUND: Despite little fluctuation in the numbers of people under community justice supervision in England and Wales, the number of deaths in this population has more than doubled between 2013-14 and 2020-21, from 560 to 1343 deaths. Contributing factors and causes of mortality are somewhat unknown. The aim of this study was to understand the number and the leading causes of people dying while under community justice supervision in Wales, UK, between April 1, 2018, and March 31, 2021. METHODS: Public Health Wales in collaboration with HM Prison and Probation Service in Wales were provided with identifiable data (name, date of birth, date of death, and the Probation Delivery Unit) of 306 individuals (aged ≥18 years) who had died during this time period while under community justice supervision. Following de-duplication and matching of National Health Service (NHS) numbers using the Welsh Demographic System, 266 deaths were linked to the live Office for National Statistics (ONS) Death Registry to obtain the cause of death. Deaths were grouped based on the International Classification of Diseases (ICD)-10 code assigned as their underlying cause of death. FINDINGS: In this cross-sectional study, the mortality rate overall was higher in women than in men (7·5 vs 5·6 deaths per 1000 population), despite the majority of deaths being in men, with less than 40 deaths in women. Mortality rates were nearly double in those aged 50 years and older (9·4 deaths per 1000 population) than in those aged 18-49 years (5·0 deaths per 1000 population). Drugs or alcohol were considered a primary cause of death for just under half of all deaths (n=115; 43%), with opiates being the most commonly named substance (n=63; 24%). 70 drug-related deaths involved poly-drug use. Accidental drug-related deaths were four times higher in those aged 18-49 years than in those aged 50 years and older (2·3 vs 0·6 deaths per 1000 population). Diseases of the circulatory system accounted for 13% (n=34) of all deaths and were 5 times higher in those aged 50 years and older than those aged 18-49 years (2·2 vs 0·4 deaths per 1000 population). INTERPRETATION: This study provides valuable insight into the leading causes of death among this cohort, notably deaths associated with substance misuse in younger age groups and with circulatory disease in older age groups. The increase in substance misuse-related deaths reflects recent national UK trends. Further research is required to understand which of these deaths were preventable. FUNDING: None.

Shifting priorities and employment choices among workers in Wales during the COVID-19 pandemic: a longitudinal analysis.

BACKGROUND: Employment is a determinant of health. The COVID-19 pandemic disrupted working lives, forcing individuals to adapt to new ways of working. These shifts might shape people's priorities and their consideration of changes for future work. We examined how these outcomes differed depending on self-reported health status. METHODS: In this longitudinal analysis, we used data from the COVID-19 Employment and Health in Wales Study; a nationally-representative household survey of workers aged 18-64 years. Timepoint 1 (T1) data were collected between May 27, 2020, and June 22, 2020, and timepoint 2 (T2) data between Nov 30, 2020, and Jan 29, 2021. Participants who responded at both timepoints were eligible. Respondents selected five employment priorities at both timepoints, and the employment changes they considered during the COVID-19 pandemic at T2 only. We used multivariable logistic regressions (including sociodemographics, current employment factors, and self-reported health) and examined associations with health firstly for employment priorities, and secondly for the consideration of employment changes. Health measures were self-reported general health, limiting pre-existing health conditions (both using National Survey for Wales validated questions), and mental wellbeing (using the shortened Warwick Edinburgh Mental Well-being Scale). FINDINGS: We analysed data from 592 respondents (382 [65%] women). 766 (56%) of 1358 T1 respondents were excluded as no T2 responses were provided. Those who self-reported poor general health were consistently more likely to prioritise flexible working arrangements than those rating fair or above (T1 adjusted odds ratio [aOR] 2·06 [95% CI 1·10-3·88], p=0·033; T2 aOR 1·87 [95% CI 1·05-3·33], p=0·034). Those with low (as opposed to average) mental wellbeing were more likely to consider securing a permanent contract (aOR 5·49 [95% CI 1·32-22·81], p=0·023, and those with limiting pre-existing conditions were four times more likely to consider becoming self-employed (aOR 4·00 [95% CI 1·35-11·84], p=0·011) than those without. INTERPRETATION: Promoting the adoption of flexible working policies and supporting those in poor health to obtain flexible employment could benefit people in Wales. Those with low mental wellbeing might seek the security of permanent employment, and those with limiting pre-existing conditions might value the autonomy of self-employment. FUNDING: None.

Mental health of the nursing and midwifery workforce in Wales during the COVID-19 pandemic: a cross-sectional analysis.

BACKGROUND: The mental health of the nursing and midwifery workforce in the UK became a public health concern before the COVID-19 pandemic. Poor mental health is a known factor for those considering leaving the profession, and workforce retention of younger members is crucial for the future of the sector. The aim of this study was to provide up-to-date estimates of mental wellbeing in this workforce in Wales during the COVID-19 pandemic. METHODS: We did a cross-sectional analysis of demographics, work-related information, and health data from respondents to a national online survey of registered and student nurses and midwives and health-care support workers in Wales. The survey was open between June 23 and Aug 9, 2021, and 2910 people responded (approximately 7% of the workforce). Mental wellbeing was calculated using the Short Warwick Edinburgh Mental Wellbeing Score (SWEMWBS). We measured probable clinical depression (SWEMWBS <18) and possible mild depression (SWEMWBS 18-20). We used χ2 analysis and multinomial logistic regression (adjusted for sex and staff grouping) to examine associations between age groups and mental wellbeing. FINDINGS: We analysed data from 2781 (95·6%) of 2910 respondents (129 respondents did not answer all seven SWEMWBS questions). Overall, 1622 (58·3%) of 2781 respondents had SWEMWBSs indicative of either probable clinical depression (863 [31·0%] of 2781) or possible mild depression (759 [27·3%] of 2781). Probable clinical depression was highest among those aged 18-29 years (180 [33·8%] of 532), 30-39 years (250 [35·6%] of 703), and 40-49 years (233 [33·5%] of 696). Respondents in these age groups were twice as likely to report SWEMWBSs indicative of probable clinical depression than respondents aged 60 years and older (18-29 years adjusted odds ratio [aOR] 2·38 [95% CI 1·43-3·97], p=0·0009; 30-39 years aOR 2·86 [1·77-4·64], p<0·0001; 40-49 years aOR 2·49 [1·54-4·02], p=0·0002). INTERPRETATION: This study highlights the substantial burden of poor mental wellbeing among the nursing and midwifery workforce in Wales, especially in those aged 49 years and younger. These figures, higher than previous estimates, could reflect the mental health effect of responding to the pandemic and could have long-term implications on workforce retention. FUNDING: None.

A Natural Language Processing and Machine Learning Approach to Identification of Incidental Radiology Findings in Trauma Patients Discharged from the Emergency Department.

STUDY OBJECTIVE: Patients undergoing diagnostic imaging studies in the emergency department (ED) commonly have incidental findings, which may represent unrecognized serious medical conditions, including cancer. Recognition of incidental findings frequently relies on manual review of textual radiology reports and can be overlooked in a busy clinical environment. Our study aimed to develop and validate a supervised machine learning model using natural language processing to automate the recognition of incidental findings in radiology reports of patients discharged from the ED. METHODS: We performed a retrospective analysis of computed tomography (CT) reports from trauma patients discharged home across an integrated health system in 2019. Two independent annotators manually labeled CT reports for the presence of an incidental finding as a reference standard. We used regular expressions to derive and validate a random forest model using open-source and machine learning software. Final model performance was assessed across different ED types. RESULTS: The study CT reports were divided into derivation (690 reports) and validation (282 reports) sets, with a prevalence of incidental findings of 22.3%, and 22.7%, respectively. The random forest model had an area under the curve of 0.88 (95% confidence interval [CI], 0.84 to 0.92) on the derivation set and 0.92 (95% CI, 0.88 to 0.96) on the validation set. The final model was found to have a sensitivity of 92.2%, a specificity of 79.4%, and a negative predictive value of 97.2%. Similarly, strong model performance was found when stratified to a dedicated trauma center, high-volume, and low-volume community EDs. CONCLUSION: Machine learning and natural language processing can classify incidental findings in CT reports of ED patients with high sensitivity and high negative predictive value across a broad range of ED settings. These findings suggest the utility of natural language processing in automating the review of free-text reports to identify incidental findings and may facilitate interventions to improve timely follow-up.

Challenges to self-isolation among contacts of cases of COVID-19: a national telephone survey in Wales.

BACKGROUND: Self-isolation is challenging and adherence is dependent on a range of psychological, social and economic factors. We aimed to identify the challenges experienced by contacts of coronavirus disease 2019 (COVID-19) cases to better target support and minimize the harms of self-isolation. METHODS: The Contact Adherence Behavioural Insights Study (CABINS) was a 15-minute telephone survey conducted with confirmed contacts of COVID-19 (N = 2027), identified through the NHS Wales Test Trace Protect (TTP) database. RESULTS: Younger people (aged 18-29 years) were three times more likely to report mental health concerns (adjusted odds ratio [aOR]: 3.16, 95% confidence interval [CI]: 2.05-4.86) and two times more likely to report loneliness (aOR: 1.96, CI: 1.37-2.81) compared to people aged over 60 years. Women were 1.5 times more likely to experience mental health concerns (aOR: 1.51, 95% CI: 1.20-1.92) compared to men. People with high levels of income precarity were eight times more likely to report financial challenges (aOR: 7.73, CI: 5.10-11.74) and three times more likely to report mental health concerns than their more financially secure counterparts (aOR: 3.08, CI: 2.22-4.28). CONCLUSION: Self-isolation is particularly challenging for younger people, women and those with precarious incomes. Providing enhanced support is required to minimize the harms of self-isolation.

Characterization of Cas12a nucleases reveals diverse PAM profiles between closely-related orthologs.

CRISPR-Cas systems comprise diverse adaptive immune systems in prokaryotes whose RNA-directed nucleases have been co-opted for various technologies. Recent efforts have focused on expanding the number of known CRISPR-Cas subtypes to identify nucleases with novel properties. However, the functional diversity of nucleases within each subtype remains poorly explored. Here, we used cell-free transcription-translation systems and human cells to characterize six Cas12a single-effector nucleases from the V-A subtype, including nucleases sharing high sequence identity. While these nucleases readily utilized each other's guide RNAs, they exhibited distinct PAM profiles and apparent targeting activities that did not track based on phylogeny. In particular, two Cas12a nucleases encoded by Prevotella ihumii (PiCas12a) and Prevotella disiens (PdCas12a) shared over 95% amino-acid identity yet recognized distinct PAM profiles, with PiCas12a but not PdCas12a accommodating multiple G's in PAM positions -2 through -4 and T in position -1. Mutational analyses transitioning PiCas12a to PdCas12a resulted in PAM profiles distinct from either nuclease, allowing more flexible editing in human cells. Cas12a nucleases therefore can exhibit widely varying properties between otherwise related orthologs, suggesting selective pressure to diversify PAM recognition and supporting expansion of the CRISPR toolbox through ortholog mining and PAM engineering.

Impact of botulinum toxin injection into the masticatory muscles on mandibular bone: A systematic review.

BACKGROUND: Botulinum toxin type A (BoNTA) injection into the masticatory muscles has been widely used to treat a number of painful and nonpainful conditions; however, no systematic reviews have been performed on the long-term effect to the mandibular bone. OBJECTIVE: Our systematic review aimed to evaluate the impact of botulinum toxin injection into the masticatory muscles on mandibular bone based. METHODS: PubMed, Embase, Ovid, CINAHL and Web of Science were searched for human studies assessing mandibular bone after injection of BoNTA using computed tomography (CT) and cone beam CT (CBCT). RESULTS: Seven studies were eligible for review; five reported significant bony changes to one or more areas of the mandible. Most frequently affected were the condylar head, coronoid process and ramus. The most frequent changes were decreased bone volume, cortical thickness and cortical and trabecular density. CONCLUSIONS: This is the first systematic review to examine an association between BoNTA injection into the masticatory muscles and mandibular bone quality. Data were analysed from a limited number of studies with a small sample size, and the quality of the included studies was very low. While the majority of available evidence suggests BoNTA injection results in bony change, further study is required to confirm a dose-dependence effect and the impact of gender and age. High-quality trials should utilise a combination of software analysis and radiologist review, with longer-term follow-up to monitor for persistence of bony effect and clinical significance.

Abundance of undiagnosed cardiometabolic risk within the population of a long-stay prison in the UK.

BACKGROUND: The health of people in prisons is a public health issue. It is well known that those in prison experience poorer health outcomes than those in the general community. One such example is the burden of non-communicable diseases, more specifically cardiovascular disease (CVD), stroke and type 2 diabetes (T2DM). However, there is limited evidence research on the extent of cardiometabolic risk factors in the prison environment in Wales, the wider UK or globally. METHODS: Risk assessments were performed on a representative sample of 299 men at HMP Parc, Bridgend. The risk assessments were 30 min in duration and men aged 25-84 years old and free from pre-existing CVD and T2DM were eligible. During the risk assessment, a number of demographic, anthropometric and clinical markers were obtained. The 10-year risk of CVD and T2DM was predicted using the QRISK2 algorithm and Diabetes UK Risk Score, respectively. RESULTS: The majority of the men was found to be either overweight (43.5%) or obese (37.5%) and/or demonstrated evidence of central obesity (40.1%). Cardiometabolic risk factors including systolic hypertension (25.1%), high cholesterol (29.8%), low HDL cholesterol (56.2%) and elevated total cholesterol: HDL ratios (23.1%) were observed in a considerable number of men. Ultimately, 15.4% were calculated at increased risk of CVD, and 31.8% predicted at moderate or high risk of T2DM. CONCLUSIONS: Overall, a substantial prevalence of previously undiagnosed cardiometabolic risk factors was observed and men in prison are at elevated risk of cardiometabolic disease at a younger age than current screening guidelines.

Factors influencing initiation of health behaviour conversations with patients: Cross-sectional study of nurses, midwives, and healthcare support workers in Wales.

AIM: To identify factors influencing healthcare professionals' engagement in health behaviour conversations with patients. DESIGN: Cross-sectional survey. METHODS: Between April and June 2019, an online survey of 1338 nurses, midwives and healthcare support workers was conducted. The survey assessed whether staff felt comfortable initiating health behaviour conversations with patients about five behaviours (reducing alcohol intake; stop smoking; being more active; reducing their weight; and improving their diet) and barriers to conversation initiation. Health professionals' own health-related behaviours, self-rated health and mental wellbeing, and socio-demographic characteristics were recorded. Logistic regression models were built to assess factors associated with feeling comfortable initiating health behaviour conversations for each topic. RESULT: Less than 50% of respondents reported feeling comfortable initiating health behaviour conversations with patients. Female staff, young professionals (18 to 29 years), those in lower staff grades and those with poorer health and low mental wellbeing were less likely to report feeling comfortable having health behaviour conversations across all topics. Those who did not adhere to physical activity and dietary guidelines were less likely to initiate a conversation about being more active and having a healthy diet, respectively. Not having time to discuss the topic, suitable space to hold a conversation, and feeling worried about offending/upsetting patients were the main barriers reported. CONCLUSION: Around 6 in 10 members of the nursing, midwifery and healthcare support workforce in Wales potentially do not feel comfortable to initiate a health behaviour conversation with patients about health and wellbeing. Feeling less comfortable to initiate a conversation was associated with staff demographics and organizational factors. IMPACT: We identified those less likely to initiate health behaviour conversations as well as personal and organizational barriers to initiation. This will help to target and tailor interventions to ensure staff are equipped and enabled to hold health behaviour conversations with patients.

Radiology as Personal Knowledge.

OBJECTIVE. The purpose of this article is to discuss the importance of radiology learners building a personal knowledge of radiology through observation, trial and error, and meaningful interaction with educators rather than through memorization of rules and algorithms. CONCLUSION. To become a radiologist is to join a community, one shaped by countless predecessors and educators, including many whose distinctive contributions remain unknown. More-experienced radiologists have a crucial role in challenging learners and showing what knowledge, skill, experience, and judgment look like in practice, as opposed to on a page or in a diagram. Radiology educators must ensure that mere data transmission never supplants the "why" of becoming a radiologist.

Investigating the prevalence of latent Tuberculosis infection in a UK remand prison.

BACKGROUND: Tuberculosis (TB) remains a major global public health issue and in low-incidence countries guidance identifies the need to screen for and treat latent tuberculosis infection (LTBI) with the prison environment recommended as a setting to perform LTBI screening. This study describes the findings of a LTBI screening programme which took place on entry to a remand prison in the UK. METHODS: Testing for LTBI was undertaken alongside screening for blood borne viruses in 567 men. During the screening process, information was collected on demographic variables and also specific risk factors based on World Health Organization recommendations. LTBI analysis was performed using Interferon-Gamma Release Assay (IGRA) technique. RESULTS: In total, 40 men returned an IGRA positive result (7.1%). However, irrespective of IGRA/LTBI status there was a substantial burden of risk factors present including previous prison stay, history of substance misuse and no BCG vaccination. Non-White ethnicity, a history of substance misuse and age over 34 years were the most significant factors in identifying individuals who would require treatment for LTBI (Positive IGRA result). CONCLUSIONS: The study further demonstrates that the prevalence of LTBI remains increased within the prison environment and is a setting that still requires effective LTBI management.

Structure of winter groundfish feeding guilds in Pacific herring Clupea pallasii and walleye pollock Gadus chalcogrammus nursery fjords.

The contents of 1056 stomachs were included in a trophic-guild analysis to document separation amongst 16 groundfish species inhabiting Pacific herring Clupea pallasii and walleye pollock Gadus chalcogrammus nursery fjords in Prince William Sound, Alaska and to determine the relative contribution of C. pallasii and G. chalcogrammus to that separation. A total of five multi-species feeding guilds and one outlier species were determined through multivariate analyses. Major gradients of trophic separation spanned from invertebrates (mostly shrimps, crabs and unidentified decapods) to fishes (mostly unidentified fishes, C. pallasii and G. chalcogrammus) a pattern that was influenced by intra and interspecific differences in predator lengths. While C. pallasii and G. chalcogrammus were important to the overall guild structure, within-guild similarities were consistently highest due to unidentified fishes. In general, larger predators consumed the largest C. pallasii and G. chalcogrammus, with the smaller-on-average predators consuming smaller C. pallasii and fewer or smaller G. chalcogrammus. Regardless of guild inclusion, groundfishes primarily consumed pre-recruit C. pallasii and G. chalcogrammus (i.e., younger than age 3 years fishes), which has the potential to negatively influence recruitment of these forage fishes to the adult, spawning population.

Partial Hand Transplant: Lessons Learned From Cadaveric Dissection Studies.

As the field of vascularized composite allotransplantation continues to expand, new upper extremity transplant candidates are being considered. We recently evaluated a bilateral amputee who had a mid-forearm amputation and a contralateral metacarpal hand amputation. In the latter limb, a "partial" hand transplant that preserved the majority of the patient's existing hand, including a partially severed thumb with intact thenar muscle function, was proposed. The feasibility of this partial hand transplant was studied in fresh-frozen cadaver limbs. This report details the proposed approach, the cadaveric dissections, and the lessons learned from these dissections. Issues of osteosynthesis, microvascular planning, and intrinsic muscle recovery are discussed, all of which are critical considerations for partial hand transplant candidates. Ultimately, the partial hand approach was felt to be inferior to a more conventional distal forearm transplant in this particular candidate. Practical, functional, and ethical implications of such decision are presented.

Patient- and Disease-Specific Factors Associated With Operative Management of de Quervain Tendinopathy.

PURPOSE: It remains unclear which factors, patient- or disease-specific, are associated with electing to undergo operative management for de Quervain tendinopathy. Our null hypothesis was that no patient- or disease-specific factors would be associated with the choice of surgical treatment of de Quervain tendinopathy. METHODS: We performed a retrospective review of consecutive patients diagnosed with de Quervain tendinopathy over 3 years by 1 of 3 fellowship-trained hand surgeons at an urban academic institution. Descriptive statistics were calculated for patient baseline and disease-specific characteristics. Cohorts were compared using bivariate analysis for all collected variables. Binary logistic regression with backward stepwise term selection was performed including independent predictors identified by bivariate analysis. RESULTS: A total of 200 patients were identified for inclusion. Bivariate analysis revealed that surgically treated patients were significantly more likely to have Medicaid insurance, psychiatric illness history, and disabled work status. Regression analysis revealed an association between surgical treatment and 2 of the factors evaluated: Medicaid insurance status and psychiatric illness history. CONCLUSIONS: Psychiatric illness and Medicaid insurance status are associated with undergoing surgical release of the first dorsal compartment. These findings support the use of a biopsychosocial framework when treating patients with de Quervain tendinopathy. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Acute Deep Infections of the Upper Extremity: The Utility of Obtaining Atypical Cultures in the Presence of Purulence.

PURPOSE: In the setting of acute deep upper extremity infections, evidence is lacking to guide the decision whether to send atypical cultures (fungal and acid-fast-bacillus [AFB]) during surgical debridement, especially in the presence of purulent fluid that is commonly observed with typical bacterial infections. Our purpose was to determine the frequency of positive atypical cultures and the frequency with which they alter treatment, and identify factors associated with positive atypical cultures. METHODS: We retrospectively identified 100 adult patients undergoing surgical debridement of acute deep infections of the upper extremity in which fungal and/or AFB cultures were sent. Necrotizing and superficial infections were excluded. Descriptive statistics were used to describe patient characteristics, infection diagnoses, number of cultures sent with corresponding rates of positivity, and treatments. Cohorts with positive and negative atypical cultures were compared with bivariate analysis for all collected variables. RESULTS: One or more immunocompromising comorbidities were present in 46% of patients. Diagnoses included soft tissue abscess (46%), suppurative flexor tenosynovitis (22%), septic arthritis (21%), osteomyelitis (9%), and septic bursitis (2%). Aerobic bacterial, anaerobic bacterial, fungal, and AFB cultures were sent in 100%, 99%, 94%, and 82% of patients, respectively. Corresponding rates of positivity were 74%, 34.3%, 5.3%, and 2.4%, respectively. Atypical cultures were positive for 7% of patients and 2.9% of all atypical tests sent. Antibiotic treatment was influenced by atypical culture data for 4% of patients. For patients with positive atypical cultures, purulence was observed during surgery in 86% of cases. Bivariate analysis demonstrated symptom duration greater than 7 days as potentially associated with atypical culture positivity. CONCLUSIONS: Intraoperative purulence at the time of surgical intervention should not deter the surgeon from obtaining atypical cultures. As expected, atypical cultures are infrequently positive given the rarity of associated diseases. Symptoms greater than 7 days may predict a higher incidence of atypical culture positivity for patients being treated surgically within 30 days of initial symptom onset. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

Transport coefficients of He(+) ions in helium.

This paper demonstrates that the transport coefficients of (4)He(+) in (4)He can be calculated over wide ranges of E/N, the ratio of the electrostatic field strength to the gas number density, with the same level of precision as can be obtained experimentally if sufficiently accurate potential energy curves are available for the X(2)Σu (+) and A(2)Σg (+) states and one takes into account resonant charge transfer. We start by computing new potential energy curves for these states and testing their accuracy by calculating spectroscopic values for the separate states. It is established that the potentials obtained by extrapolation of results from d-aug-cc-pVXZ (X = 6, 7) basis sets using the CASSCF+MRCISD approach are each in exceptionally close agreement with the best potentials available and with experiment. The potentials are then used in a new computer program to determine the semi-classical phase shifts and the transport cross sections, and from these the gaseous ion transport coefficients are determined. In addition, new experimental values are reported for the mobilities of (4)He(+) in (4)He at 298.7 K, as a function of E/N, where careful consideration is given to minimizing various sources of uncertainty. Comparison with previously measured values establishes that only one set of previous data is reliable. Finally, the experimental and theoretical ion transport coefficients are shown to be in very good to excellent agreement, once corrections are applied to account for quantum-mechanical effects.

Comparison of the metabolic responses to ingestion of hydrothermally processed high-amylopectin content maize, uncooked maize starch or dextrose in healthy individuals.

Optimal carbohydrate ingestion strategies as nutritional therapy for glycogen storage diseases have not been fully realised, in part, due to difficulties in accessing patient cohorts, alongside limited details on metabolic effects and insight into working mechanisms. The present pilot study compared glycaemic and fuel oxidation responses following the ingestion of a hydrothermally processed maize starch (HPMS), an uncooked maize starch (UCMS) and maize-derived dextrose (DEX) at rest and during and after exercise in healthy individuals. A total of eight participants (seven males and one female; body mass (BM) 76.9 (SEM 5.2) kg) visited the laboratory on three occasions. During each visit, the participants ingested 1 g/kg BM of HPMS (Glycosade™), UCMS (Argo™) or DEX as a 10% solution. Blood samples were collected over a 2 h rest period and for 2 h after a 60 min treadmill run at 65 (SEM 1) % VO(2max). Mean values with their standard errors were analysed using repeated-measures ANOVA. Blood glucose concentrations under the HPMS condition were significantly elevated from resting values at 90 min (P=0.02) after ingestion compared with those under the UCMS (60 min; P=0.02) and DEX (30 min; P=0.001) conditions. The rate of carbohydrate use during exercise after the ingestion of HPMS was 7-9% lower compared with that after the ingestion of either DEX or UCMS (P<0.05). The total amount of lipids oxidised during exercise was greater under the HPMS condition (26.2 (SEM 2.8) g) compared with that oxidised under the UCMS (19.6 (SEM 2.7) g; P=0.04) or DEX (20.6 (SEM 3.6) g; P=0.07) condition. The results demonstrated a glycaemic advantage to the ingestion of HPMS over that of UCMS or DEX. Carbohydrate oxidation was reduced after the ingestion of HPMS compared with that after the ingestion of UCMS or DEX, with a corresponding higher rate of endogenous lipid use during exercise.