A recent Perspective article described the “carbohydrate-insulin model (CIM)” of obesity, asserting that it “better reflects knowledge on the biology of weight control” as compared with what was ...described as the “dominant energy balance model (EBM),” which fails to consider “biological mechanisms that promote weight gain.” Unfortunately, the Perspective conflated and confused the principle of energy balance, a law of physics that is agnostic as to obesity mechanisms, with the EBM as a theoretical model of obesity that is firmly based on biology. In doing so, the authors presented a false choice between the CIM and a caricature of the EBM that does not reflect modern obesity science. Here, we present a more accurate description of the EBM where the brain is the primary organ responsible for body weight regulation operating mainly below our conscious awareness via complex endocrine, metabolic, and nervous system signals to control food intake in response to the body’s dynamic energy needs as well as environmental influences. We also describe the recent history of the CIM and show how the latest “most comprehensive formulation” abandons a formerly central feature that required fat accumulation in adipose tissue to be the primary driver of positive energy balance. As such, the new CIM can be considered a special case of the more comprehensive EBM but with a narrower focus on diets high in glycemic load as the primary factor responsible for common obesity. We review data from a wide variety of studies that address the validity of each model and demonstrate that the EBM is a more robust theory of obesity than the CIM.
•Vapocoolant reduces pain associated with vaccination in adults and children.•Ice reduces pain associated with vaccination in adults but not children.•Pain mitigation may also depend on vaccine/s ...administered.•Efficacy/applicability of skin cooling in primary health requires further research.
Vaccine injections are the most common cause of iatrogenic pain in childhood and a cause of anxiety in adulthood. Skin cooling techniques, including icepacks and vapocoolants, may provide pain relief during intramuscular injections.
To identify the effects of skin cooling techniques on pain associated with immunisation.
MEDLINE (Ovid), CINAHL, EMCARE, INFORMIT and Scopus were searched for randomised controlled trials (RCTs) investigating the use of skin cooling techniques on pain associated with vaccination. Study and intervention details, outcomes measures and results were extracted and risk of bias assessed using the Cochrane Risk of Bias tool. Due to heterogeneity of studies, a narrative synthesis was performed.
Thirteen trials were included, involving 689 paediatric and 829 adult participants. All studies used vapocoolant or ice as one of the interventions. Comparator groups included topical EMLA cream, breastfeeding, distraction techniques and tactile stimulation. Vapocoolant reduced vaccination-related pain in all adult studies and six paediatric studies however the use of ice packs in paediatric patients was not effective.
The use of cooling techniques reduces pain associated with vaccinations in adults. Paediatric studies show mixed results for vapocoolants and an inability for ice to decrease vaccine-injection pain. Larger RCTs are required to determine the most effective administration techniques and optimise the analgesic effects of skin cooling.
Aims
Pelvic floor muscle training (PFMT) is a first line conservative treatment for men with urinary dysfunction, but reports of its efficacy are variable. This study aimed to systematically review ...the content of PFMT programs used for urinary dysfunction in men.
Methods
Electronic databases (PubMed, CINAHL, EMBASE, Cochrane, PEDro) were searched for studies that used PFMT in the treatment of adult men with urinary dysfunction. Details of PFMT treatment sessions and home exercise protocols were extracted. Criteria specific to PFMT were developed, based on the Consensus on Exercise Reporting Template, and applied to all studies to measure the comprehensiveness of the PFMT description in the manuscript.
Results
Results from the 108 included studies indicate substantial heterogeneity in both the content of PFMT and the quality of reporting of the components of the exercise regimes. There was notable disparity in the muscles targeted by the interventions (and few focused on urethral control despite the use in management of urinary conditions) and the intensity of the programs (eg, 18‐240 contractions per day). Most studies were missing key details of description of the PFMT programs (eg, the position in which the pelvic floor muscle PFM contraction was taught and how it was assessed, methods used to ensure exercise adherence).
Conclusions
Variation in content of PFMT programs is likely to contribute to variation in the reported efficacy for management of urinary dysfunction in men, and unclear description of the details of the evaluated programs makes it difficult to identify the effective/ineffective components. PROSPERO registration number CRD42017071038.
Aims
Efficacy of pelvic floor muscle training (PFMT) for postprostatectomy incontinence (PPI) differs between randomized clinical trials (RCT). This might be explained by variation in ...content/delivery of PFMT (eg, biofeedback, muscles targeted, and time of commencement of training). This review investigated whether outcome of meta‐analysis differs based on presence or not of specific RCT features.
Methods
PubMed, CINAHL, EMBASE, Physiotherapy Evidence Database (PEDro), and Cochrane were searched for RCTs that investigated efficacy of PFMT on PPI. PFMT details and outcomes were extracted. Methodological quality and comprehensiveness of PFMT reporting was assessed using the PEDro scale and Consensus on Reporting Template, respectively. Effect size and 95% confidence intervals were calculated for incontinence rate at 3 months. To identify features that influenced efficacy, separate meta‐analyses were performed for studies with and without specific features.
Results
Twenty‐two trials were included, and 15 were used for meta‐analysis of 3‐month outcomes. Overall, meta‐analysis showed reduced incontinence with PFMT (risk ratio RR = 0.85; I2= 55%; P = .005). Meta‐analyses showed better outcomes for PFMT than control groups when the study included preoperative PFMT (RR = 0.76; I2= 30%; P = .006), biofeedback (RR = 0.73; I2= 58%; P = .006), instruction to contract around the urethra (RR = 0.9; I2= 43%; P = .009), a control group without PFMT instruction (RR = 0.85; I2= 69%; P = .05), inclusion of all men irrespective of continence status (RR = 0.84; I2= 30%; P = .003) and continence defined as no leakage (RR = 0.85; I2= 48%; P = .05).
Conclusions
Preoperative PFMT, biofeedback, urethral instructions, no PFMT instruction for controls, inclusion of all men, and continence defined as no leakage are features associated with successful patient outcomes. Future studies should consider these features in design of interventions and pooling data for meta‐analysis.
Cryptococcosis remains the leading cause of fungal meningitis worldwide, caused primarily by the pathogen Cryptococcus neoformans. Symptomatic cryptococcal infections typically affect ...immunocompromised patients. However, environmental exposure to cryptococcal spores is ubiquitous and most healthy individuals are thought to harbor infections from early childhood onwards that are either resolved, or become latent. Since macrophages are a key host cell for cryptococcal infection, we sought to quantify the extent of individual variation in this early phagocyte response within a small cohort of healthy volunteers with no reported immunocompromising conditions. We show that rates of both intracellular fungal proliferation and non-lytic expulsion (vomocytosis) are remarkably variable between individuals. However, we demonstrate that neither gender, in vitro host inflammatory cytokine profiles, nor polymorphisms in several key immune genes are responsible for this variation. Thus the data we present serve to quantify the natural variation in macrophage responses to this important human pathogen and will hopefully provide a useful "benchmark" for the research community.
Accurate measurement of free-living energy intake (EI) over long periods is imperative for understanding obesity and its treatment. Unfortunately, traditional methods rely on self-report and are ...notoriously inaccurate. Although EI can be indirectly estimated by the intake-balance method, this technique is prohibitively labor-intensive and expensive, requiring repeated measures of energy expenditure via doubly labeled water (DLW) along with multiple dual-energy X-ray absorptiometry (DXA) scans to measure changes in body energy stores.
Our objective was to validate a mathematical method to measure long-term changes in free-living energy intake.
We measured body weight and EI changes (ΔEI) over 4 time intervals by using the intake-balance method in 140 individuals who underwent 2 y of caloric restriction as part of the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy study. We compared the ΔEI values calculated by using DLW/DXA with those obtained by using a mathematical model of human metabolism whose only inputs were the initial demographic information and repeated body weight data.
The mean ΔEI values calculated by the model were within 40 kcal/d of the DLW/DXA method throughout the 2-y study. For individual subjects, the overall root mean square deviation between the model and DLW/DXA method was 215 kcal/d, and most of the model-calculated ΔEI values were within 132 kcal/d of the DLW/DXA method.
Accurate and inexpensive estimates of ΔEI that are comparable to the DLW/DXA method can be obtained by using a mathematical model and repeated body weight measurements.
Cryptococcus gattii is an emerging intracellular pathogen and the cause of the largest primary outbreak of a life-threatening fungal disease in a healthy population. Outbreak strains share a unique ...mitochondrial gene expression profile and an increased ability to tubularize their mitochondria within host macrophages. However, the underlying mechanism that causes this lineage of C. gattii to be virulent in immunocompetent individuals remains unexplained. Here we show that a subpopulation of intracellular C. gattii adopts a tubular mitochondrial morphology in response to host reactive oxygen species. These fungal cells then facilitate the rapid growth of neighbouring C. gattii cells with non-tubular mitochondria, allowing for effective establishment of the pathogen within a macrophage intracellular niche. Thus, host reactive oxygen species, an essential component of the innate immune response, act as major signalling molecules to trigger a 'division of labour' in the intracellular fungal population, leading to increased pathogenesis within this outbreak lineage.
While the field of mixed methods has discussed complexity theory, more clarification regarding its conceptualization is needed. Accordingly, we first review how various fields have interpreted and ...applied the central ideas of complexity theory in the social sciences. We then analyze two empirical studies that used complexity theory and mixed methods. We highlight how both studies examined complex systems, used elements of complexity theory as their theoretical framework, and used complexity–congruent methodologies and methods. To conclude, we offer conceptual and methodological implications for using complexity theory for mixed methods research. We view the clarification provided an important contribution to the field of mixed methods as it assists researchers in studying complex systems, theorizing complex phenomena, and using complex methods.
Delirium, an acute organ dysfunction, is common among critically ill patients leading to significant morbidity and mortality; its epidemiology in a mixed cardiology and cardiac surgery ICU is not ...well established. We sought to determine the prevalence and risk factors for delirium among cardiac surgery ICU patients.
Prospective observational study.
Twenty-seven-bed medical-surgical cardiac surgery ICU.
Two hundred consecutive patients with an expected cardiac surgery ICU length of stay >24 hrs.
None.
Baseline demographic data and daily assessments for delirium using the validated and reliable Confusion Assessment Method for the ICU were recorded, and quantitative tracking of delirium risk factors were conducted. Separate analyses studied the role of admission risk factors for occurrence of delirium during the cardiac surgery ICU stay and identified daily occurring risk factors for the development of delirium on a subsequent cardiac surgery ICU day.
Prevalence of delirium was 26%, similar among cardiology and cardiac surgical patients. Nearly all (92%) exhibited the hypoactive subtype of delirium. Benzodiazepine use at admission was independently predictive of a three-fold increased risk of delirium (odds ratio 3.1 1, 9.4, p = 0.04) during the cardiac surgery ICU stay. Of the daily occurring risk factors, patients who received benzodiazepines (2.6 1.2, 5.7, p = 0.02) or had restraints or devices that precluded mobilization (2.9 1.3, 6.5, p < 0.01) were more likely to have delirium the following day. Hemodynamic status was not associated with delirium.
Delirium occurred in one in four patients in the cardiac surgery ICU and was predominately hypoactive in subtype. Chemical restraints via use of benzodiazepines or the use of physical restraints/restraining devices predisposed patients to a greater risk of delirium, pointing to areas of quality improvement that would be new to the vast majority of cardiac surgery ICUs.
The pathogenic fungus
enters the human host via inhalation into the lung and is able to reside in a niche environment that is serum- (opsonin) limiting. Little is known about the mechanism by which ...nonopsonic phagocytosis occurs via phagocytes in such situations. Using a combination of soluble inhibitors of phagocytic receptors and macrophages derived from knockout mice and human volunteers, we show that uptake of nonopsonized
and
via the mannose receptor is dependent on macrophage activation by cytokines. However, although uptake of
is via both dectin-1 and dectin-2,
uptake occurs largely via dectin-1. Interestingly, dectin inhibitors also blocked phagocytosis of unopsonized Cryptococci in wax moth (
) larvae and partially protected the larvae from infection by both fungi, supporting a key role for host phagocytes in augmenting early disease establishment. Finally, we demonstrated that internalization of nonopsonized Cryptococci is not accompanied by the nuclear translocation of NF-κB or its concomitant production of proinflammatory cytokines such as TNF-α. Thus, nonopsonized Cryptococci are recognized by mammalian phagocytes in a manner that minimizes proinflammatory cytokine production and potentially facilitates fungal pathogenesis.
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