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Background The Improving the Wellbeing of people with Opioid Treated CHronic pain (I-WOTCH) randomised controlled trial found that a group-based educational intervention to support people using strong opioids for chronic non-malignant pain helped a significant proportion of people to stop or decrease opioid use with no increase in pain-related disability. We report a linked process evaluation of the group-based intervention evaluated in comparison to a usual-care control group that received a self-help booklet and relaxation CD.Methods We interviewed 18 intervention facilitators, and 20 intervention and 20 control participants who had chronic non-malignant pain and were recruited from general (family) practices in the UK. Quantitative data included change mechanism questions on the trial questionnaires which explored motivation, expectations and self-efficacy. Fidelity was assessed by listening to a sample of audio-recorded group sessions and nurse consultations. Quantitative and qualitative data were integrated using ‘follow a thread’ and a mixed-methods matrix.Findings Four overarching themes emerged: (1) the right time to taper, (2) the backdrop of a life with chronic pain, (3) needing support and (4) the benefits of being in a group. Delivery fidelity was good, adherence (83%) and competence (79%) across a range of intervention groups. Staff delivering the intervention found three typical responses to the intervention: resistance, open to trying and feeling it was not the right time. The group experience was important to those in the intervention arm. It provided people with a forum in which to learn about the current thinking about opioid usage and its effects. It also gave them examples of how feasible or personally relevant coming off opioids might be.Conclusion The process evaluation data showed that the I-WOTCH intervention was well delivered, well received and useful for most interviewees. Being ‘the right time’ to taper and having support throughout tapering, emerged as important factors within the context of living with chronic pain.Trial registration number ISRCTN49470934.

Epidemiologic data show that both current and previous tuberculosis (TB) increase the risk of in-hospital mortality from coronavirus disease-2019 (COVID-19), and there is a similar trend for poor outcomes from Mycobacterium tuberculosis (Mtb) infection after recent SARS-CoV-2. A shared dysregulation of immunity explains the dual risk posed by co-infection, but the specific mechanisms are being explored. While initial attention focused on T cell immunity, more comprehensive analyses revealed a dysfunctional innate immune response in COVID-19, characterized by reduced numbers of dendritic cells, NK cells and a redistribution of mononuclear phagocytes towards intermediate myeloid subsets. During hyper- or chronic inflammatory processes, activation signals from molecules such as growth factors and alarmins lead to the expansion of an immature population of myeloid cells called myeloiddeprived suppressor cells (MDSC). These cells enter a state of pathological activation, lose their ability to rapidly clear pathogens, and instead become broadly immunosuppressive. MDSC are enriched in the peripheral blood of patients with severe COVID-19; associated with mortality; and with higher levels of inflammatory cytokines. In TB, MDSC have been implicated in loss of control of Mtb in the granuloma and ineffective innate and T cell immunity to the pathogen. Considering that innate immune sensing serves as first line of both anti-bacterial and anti-viral defence mechanisms, we propose MDSC as a crucial mechanism for the adverse clinical trajectories of TB-COVID-19 coinfection. [ABSTRACT FROM AUTHOR]

Introduction: Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan African populations are sparse. Methods: We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic. A second sample from the same patients was collected on day 7 of ICU admission. Patients were followed up until in-hospital death or hospital discharge. A custom-designed 52 biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between biomarkers and mortality based on pre-determined functional groups, and individual analytes. Results: Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines, chemokines, and acute phase reactants, as well as reduced levels of regulatory T cell cytokines. Interleukin (IL)-15 and IL-18 were elevated in those who died, and levels reduced over time in those who survived. Procalcitonin (PCT), C-reactive protein, Endothelin-1 and vascular cell adhesion molecule-1 were elevated in those who died. Discussion: These results show the pattern of dysregulation in critical COVID-19 in a Sub-Saharan African cohort. They suggest that fatal COVID-19 involved excessive activation of cytotoxic cells and the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome. Furthermore, superinfection and endothelial dysfunction with thrombosis might have contributed to mortality. HIV infection did not affect the outcome. A clinically relevant biosignature including PCT, pH and lymphocyte percentage on differential count, had an 84.8% sensitivity for mortality, and outperformed the Luminex-derived biosignature. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe and compare veterinary professionals' use of shared decision-making during companion animal appointments. DESIGN: Multi-practice cross-sectional study. SAMPLE: A purposive sample of 4 companion animal veterinary clinics in a group practice in Texas. PROCEDURES: A convenience sample of veterinary appointments were recorded January to March 2018 and audio-recordings were analyzed using the Observer OPTIONS instrument to assess shared decision-making. Each decision was categorized by veterinary professional involvement. RESULTS: A total of 76/85 (89%) appointments included at least 1 decision between the client and veterinary professional(s), with a total of 129 shared decisions. Decisions that involved both a veterinary technician and veterinarian scored significantly higher for elements of shared decision-making (OPTIONS = 29.5 + 8.4; n = 46), than veterinarian-only decisions (OPTIONS = 25.4 + 11.50; P = .040; n = 63), and veterinary technician-only decisions (OPTION5 = 22.5 + 7.15; P = .001; n = 20). Specific elements of shared decision-making that differed significantly based on veterinary professional involvement included educating the client about options (OPTION5 Item 3; P = .0041) and integrating the client's preference (OPTION5 Item 5; P = .0010). CLINICAL RELEVANCE: Findings suggest that clients are more involved in decision making related to their pet's health care when both the veterinary technician and veterinarian communicate with the client. Veterinary technicians' communication significantly enhanced client engagement in decision-making when working collaboratively with the veterinarian. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the impact of a 15-month, in-practice communication skills intervention on client visit satisfaction. SAMPLE 4 purposely selected veterinary clinics, 9 veterinarians, and 930 appointment-specific client satisfaction surveys. PROCEDURES The study was designed as a multipractice, preintervention-postintervention study. Practice teams participated in a 15-month communication skills intervention that included interactive group workshops and one-on-one communication coaching with the entire practice. Client Satisfaction Questionnaires were completed 3 months before (mean, 55 questionnaires/veterinarian) and after (mean, 48 questionnaires/veterinarian) the intervention. The impact of the intervention and factors associated with client visit satisfaction were evaluated with mixed logistic regression. RESULTS Client satisfaction scores were dichotomized owing to extreme negative skewness. In total, 57% (284/496) of clients were completely satisfied on pretest questionnaires, and 67% (290/434) were completely satisfied on postintervention questionnaires. The odds of clients being completely satisfied were significantly higher after the communication skills intervention (OR = 1.56; P = .002). When controlling for the intervention, predictors of client visit satisfaction included appointment type (odds of being completely satisfied were significantly higher for recheck appointments than for preventative care appointments [OR = 1.71; P = .02] and health problem appointments [OR = 1.99; P = .003]) and duration of the veterinarian-client relationship (probability increased by 0.52 with each 1-year increase in relationship duration; P = .008). CLINICAL RELEVANCE Results suggested that the client-centered, skills-based communication intervention resulted in increased client visit satisfaction. Findings contribute to current evidence that client-centered communication and duration of the veterinarian-client relationship promote client satisfaction during veterinary visits. [ABSTRACT FROM AUTHOR]

* Montessori, Dewey, and Capitalism: Educational Theory for a Free Market in Education By Jerry Kirkpatrick Claremont, Calif.: TLJ Books, 2008. Pp. 212. $18.95 paper. As Thomas Jefferson famously said, [...]

Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR • Autologous breast reconstruction is increasingly preferred over implants in the setting of radiation therapy. • Use of patient-reported outcomes is endorsed. • Shape and size of reconstructed breasts can hinder radiotherapy planning. • There is a need for randomised phase III trials. [ABSTRACT FROM AUTHOR]

* The Locavore's Dilemma: In Praise of the 10,000-Mile Diet By Pierre Desrochers, and Hiroko Shimizu New York: Public Affairs, 2012. Pp. 288. $26.99 cloth. One rarely patronizes a gourmet [...]

The influence of smoke-derived or air pollution-derived cytoplasmic particulate matter (PM) can be detrimental and can lead to failed lung immunity. We investigated mycobacterial uptake, intracellular replication, and soluble immune-mediator responses of human bronchoalveolar lavage cells (BALCs) loaded with/without PM, to infection with mycobacterial strains. We observed that only BALCs containing PM display an ex vivo phenotypic profile dominated by spontaneous interleukin (IL)-10 production. PMloaded BALCs retained the ability to phagocytose both Mycobacterium bovis Bacille Calmette Guerin (BCG) and Mycobacterium tuberculosis (M.tb) ΔleuDΔpanCD at equal efficacy as clear non-PM-loaded BALCs. However, immune responsiveness, such as the production of IL-6 (P = 0.015) and tumor necrosis factor-α (TNF)-α (P = 0.0172) immediately post M. bovis BCG infection, were dramatically lower in black BALCs loaded with PM versus clear non-PM-loaded BALCs. By 24 h post infection, differential immune responses to M. bovis BCG between black versus clear BALC waned, and instead, production of IL-6 (P = 0.03) and IL-1a (P = 0.04) by black BALCs was lower versus clear BALCs following M.tb ΔleuDΔpanCD infection. Considering that TNF-α and IL-6 are characterized as critical to host protection against mycobacteria, our findings suggest that BALCs loaded with inhaled PM, display lower levels of antimycobacterial mediators and that the response magnitude differs according to infective mycobacterial strain. Even though this did not translate into altered mycobacterial killing at early time points post infection, the long-term impact of such changes remains to be established. [ABSTRACT FROM AUTHOR]

The most important question for conservatives today is not who will be the GOP presidential candidate in 1996. It is whether Republican congressional leaders will honor their Contract With America [...]

Collapse: How Societies Choose to Fail or Succeed By Jared Diamond New York: Viking, 2005. Pp. 592. $29.95 cloth, $17.00 paperback. A fascinating book lies within the nearly six hundred [...]

Background: Inequality is rife throughout South Africa. The first wave of COVID-19 may have affected people in lower socioeconomic groups worse than the affluent. The SARS-CoV-2 seroprevalence and the specificity of anti-SARS-CoV-2 antibody tests in South Africa is not known. Methods: We tested 405 volunteers representing all socioeconomic strata from the workforce of a popular shopping and tourist complex in central Cape Town with the Abbott SARS-CoV-2 IgG assay. We assessed the association between antibody positivity and COVID-19 symptom status, medical history, and sociodemographic variables. We tested 137 serum samples from healthy controls collected in Cape Town prior to the COVID-19 pandemic, to confirm the specificity of the assay in the local population. Results: Of the 405 volunteers tested one month after the first peak of the epidemic in Cape Town, 96(23.7%) were SARS-CoV-2 IgG positive. Of those who tested positive, 46(47.9%) reported no symptoms of COVID-19 in the previous 6 months. Seropositivity was significantly associated with living in informal housing, residing in a subdistrict with low income-per household, and having a low-earning occupation. The specificity of the assay was 98.54%(95%CI 94.82%-99.82%) in the pre-COVID controls. Conclusions: There is a high background seroprevalence in Cape Town, particularly in people of lower socioeconomic status. Almost half of cases are asymptomatic, and therefore undiagnosed by local testing strategies. These results cannot be explained by low assay specificity. [ABSTRACT FROM AUTHOR]

OBJECTIVE To describe how North American veterinary medical teaching institutions VMTIs) provide communication skills training to students. SAMPLE Faculty coordinators of communication skills training programs (CSTPs) at 30 North American VMTIs. PROCEDURES An online survey instrument was designed and administered to each respondent followed by a telephone (n = 28) or in-person (2) interview. The survey and interview process were designed to evaluate all aspects of CSTPs, such as communication framework used, program format, number of student-contact hours, staffing models, outcome assessment, faculty background, program priorities, and challenges. Descriptive results were generated, and guidelines for future development of CSTPs were recommended. RESULTS 27 US and 3 Canadian VMTIs were represented, and communication skills training was required at all. Twenty-five CSTPs used the Calgary-Cambridge Guide framework. Respondents provided a mean of 33 student-contact hours of training, primarily in the first 3 years of the veterinary curriculum in lecture (mean, 12 hours), communication laboratory (13 hours), and self-study (8 hours) formats with formative feedback. Communication skills training was integrated with other disciplines at 27 VMTIs. Most CSTPs were coordinated and taught by I faculty member with a < 0.50 full-time equivalent commitment and no administrative support. Stated priorities included acquisition of resources for CSTP faculty, administrative support, and video-equipped facilities; increasing integration of CSTPs into curricula; and assessment of educational outcomes. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that support for CSTPs and recognition of their value continue to grow, but a lack of resources, faculty expertise, validated methods for outcomes assessment, and leadership remain challenges. [ABSTRACT FROM AUTHOR]

Summary: Peptide hormones are implicated in many important aspects of plant life and are usually synthesized as precursor proteins. In contrast to animals, data for plant peptide hormone maturation are scarce and the specificity of processing enzyme(s) is largely unknown. Here we tested a hypothesis that processing of prosystemin, a precursor of tomato (Solanum lycopersicum) wound hormone systemin, is performed by phytaspases, aspartate‐specific proteases of the subtilase family. Following the purification of phytaspase from tomato leaves, two tomato phytaspase genes were identified, the cDNAs were cloned and the recombinant enzymes were obtained after transient expression in Nicotiana benthamiana. The newly identified tomato phytaspases hydrolyzed prosystemin at two aspartate residues flanking the systemin sequence. Site‐directed mutagenesis of the phytaspase cleavage sites in prosystemin abrogated not only the phytaspase‐mediated processing of the prohormone in vitro, but also the ability of prosystemin to trigger the systemic wound response in vivo. The data show that the prohormone prosystemin requires processing for signal biogenesis and biological activity. The identification of phytaspases as the proteases involved in prosystemin maturation provides insight into the mechanisms of wound signaling in tomato. Our data also suggest a novel role for cell death‐related proteases in mediating defense signaling in plants. [ABSTRACT FROM AUTHOR]

Whereas research in the craniosacral field tends to focus on the benefits for the individual, in this paper I go a step further to argue that because of its psychoid nature, biodynamic craniosacral therapy (BCST) acts as an embodied practice to raise earth consciousness at both the collective and individual levels. The therapy is a light-touch practice grounded in empathetic presence in which practitioners work to attune the subtle rhythms of their own body, the client's body, and the "body" of the environment and natural world in which they meet. Referencing my clinical experience, the essay proposes that craniosacral biodynamics, bringing consciousness to the human organism, may offer a felt experience of the interconnectedness of all being, even bringing to consciousness our relationship with the earth itself. This essay highlights where Jungian theory and BCST not only overlap but also where they might support each other to revision our relationship to the planet. [ABSTRACT FROM AUTHOR]