Dietary conjugated linoleic acid (CLA) reduces body fat in animals and some humans. Here we show that trans-10, cis-12 CLA, but not cis-9, trans-11 CLA, when added to cultures of stromal vascular ...cells containing newly differentiated human adipocytes, caused a time-dependent decrease in triglyceride content, insulin-stimulated glucose and fatty acid uptake, incorporation into lipid, and oxidation compared with controls. In parallel, gene expression of peroxisome proliferator-activated receptor-gamma and many of its downstream targets were diminished by trans-10, cis-12 CLA, whereas leptin gene expression was increased. Prior to changes in gene expression and metabolism, trans-10, cis-12 CLA caused a robust and sustained activation of mitogen-activated protein kinase kinase/extracellular signal-related kinase (MEK/ERK) signaling. Furthermore, the trans-10, cis-12 CLA-mediated activation of MEK/ERK could be attenuated by pretreatment with U0126 and pertussis toxin. In parallel, pretreatment with U0126 blocked the ability of trans-10, cis-12 CLA to alter gene expression and attenuate glucose and fatty acid uptake of the cultures. Intriguingly, the induction by CLA of MEK/ERK signaling was linked to hypersecretion of adipocytokines interleukin-6 and interleukin-8. Collectively, these data demonstrate for the first time that trans-10, cis-12 CLA decreases the triglyceride content of newly differentiated human adipocytes by inducing MEK/ERK signaling through the autocrine/paracrine actions of interleukins-6 and 8.
Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery ...and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.
We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.
Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.
Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management.
The UK National Institute for Health Research Health Technology Assessment Programme.
Background:
The significance of dipstick or microscopic hematuria in pregnancy is uncertain, with some studies suggesting this is associated with a greater risk for preeclampsia. We sought to ...determine the prevalence and clinical significance of microscopic hematuria during pregnancy.
Methods:
This was a prospective case-control study in the antenatal Clinic of St George Hospital, Kogarah, Australia, a teaching hospital without tertiary referral antenatal care, with approximately 2,600 deliveries per year. One thousand pregnant women attending for routine antenatal care were invited to have a routine urinalysis performed and be referred to a nephrology clinic for further investigation if dipstick microscopic hematuria was detected on more than 1 occasion before 32 weeks’ gestation. Main outcome measures were the prevalence of dipstick hematuria, prevalence of hematuria confirmed by urine microscopy, and the development of preeclampsia or gestational hypertension or delivery of a small-for-gestational-age baby.
Results:
One hundred seventy-eight of 902 women (20%) who entered the study had dipstick hematuria on at least 2 occasions in pregnancy; 66 of 126 women (53%) who had hematuria before 32 weeks attended the nephrology clinic, where microscopic hematuria was confirmed in 40 women (61%). Renal imaging results were normal in all except 1 woman, and all women had a serum creatinine level of 0.90 mg/dL or less (≤80 μmol/L). The development of preeclampsia or gestational hypertension or delivery of a small-for-gestational-age baby were similar in women with and without dipstick hematuria. Microscopic hematuria persisted in half (15 women) of those who attended for follow-up after 3 months postpartum.
Conclusion:
Dipstick hematuria is very common during pregnancy, but rarely signifies a disorder likely to impact on the pregnancy outcome. Postpartum follow-up is recommended to detect women who have persistent hematuria and presumed underlying mild glomerulonephritis.
Division of labor in social groups is affected by the relative costs and benefits of conducting different tasks. However, most studies have examined the dynamics of division of labor, rather than the ...costs and benefits that presumably underlie the evolution of such systems. In social insects, division of labor may be simplistically described as a source-sink system, with external tasks, such as foraging, acting as sinks for the work force. The implications of two distinct sinks – foraging and waste-heap working – for division of labor were examined in the leaf-cutting ant Atta colombica. Intrinsic mortality rates were similar across external task groups. Exposure to waste (a task-related environment) led to a 60% increase in the mortality rate of waste-heap workers compared to workers not exposed to waste. Given the small number of workers present in the waste-heap task group, such increases in mortality are unlikely to affect division of labor and task allocation dramatically, except perhaps under conditions of stress.
A key responsibility of the healthcare system is to develop a sustainable workforce through education and training.
The complexity of postgraduate medical education and training in Australia ...requires:
➢recognition that there are many stakeholders (junior medical officers, registrars, teaching clinicians, health departments, governments, colleges and society) with overlapping but competing interests and responsibilities;
➢a national dialogue to clarify the necessary resource investments and to assign explicit accountabilities; and
➢improved coordination and governance, while maintaining appropriate flexibility.
In other countries, stronger mechanisms of governance for oversight of postgraduate medical education have emerged, and Australia can learn from these.
Ischemic stroke (IS) is a multifactorial disorder with strong evidence from twin, family, and animal model studies suggesting a genetic influence on risk and prognosis. Several candidate genes for IS ...have been proposed, but few have been replicated. We investigated the contribution of 67 candidate genes (369 single nucleotide polymorphisms SNPs) on the risk of IS in a North American population of European descent.
Two independent studies were performed. In the first, 342 SNPs from 52 candidate genes were genotyped in 307 IS cases and 324 control subjects. The SNPs significantly associated with IS were tested for replication in another cohort of 583 IS cases and 270 control subjects. In the second study, 212 SNPs from 62 candidate genes were analyzed in 710 IS cases with subtyping available and 3751 control subjects.
None of the candidate genes (SNPs) were significantly associated with IS risk independent of known stroke risk factors after correction for multiple hypotheses testing.
These results are consistent with previous meta-analyses that demonstrate an absence of genetic association of variants in plausible candidate genes with IS risk. Our study suggests that the effect of the investigated SNPs may be weak or restricted to specific populations or IS subtypes.
Lesions in the corpus callosum in multiple sclerosis (MS) include those that are hyperintense on T2-weighted images, which can be either focal (isolated) or connected, but there is evidence that the ...corpus callosum, similar to other white matter regions, contains normal appearing white matter (NAWM) which is abnormal based on quantitative MR methodologies. In this pilot study, diffusion tensor based measures were determined in corpus callosum from 10 patients with MS and 12 age and gender matched controls. T2-hyperintense lesions were carefully segmented out from normal appearing corpus callosum to minimize contamination of the NAWM fraction with these lesions. The orientationally averaged diffusion coefficient was increased and the fractional anisotropy reduced in the NAWM fraction of the MS patients. These results confirm prior studies which suggest that pathology in the NAWM occurs independent of focal MS lesions, and are not likely the result of sample contamination through or across slices. This injury to the NAWM may be the result of focal, microscopic T2-invisible lesions and/or secondary degeneration related to distant lesions whose related fibres cross the corpus callosum.
Chronic lung allograft dysfunction (CLAD) remains the major complication limiting long‐term survival among lung transplant recipients (LTRs). Limited understanding of CLAD immunopathogenesis and a ...paucity of biomarkers remain substantial barriers for earlier detection and therapeutic interventions for CLAD. We hypothesized the airway transcriptome would reflect key immunologic changes in disease. We compared airway brush‐derived transcriptomic signatures in CLAD (n = 24) versus non‐CLAD (n = 21) LTRs. A targeted assessment of the proteome using concomitant bronchoalveolar lavage (BAL) fluid for 24 cytokines/chemokines and alloimmune T cell responses was performed to validate the airway transcriptome. We observed an airway transcriptomic signature of differential genes expressed (DGEs) in CLAD marked by Type‐1 immunity and striking upregulation of two endogenous immune regulators: indoleamine 2, 3 dioxygenase 1 (IDO‐1) and tumor necrosis factor receptor superfamily 6B (TNFRSF6B). Advanced CLAD staging was associated with a more intense airway transcriptome signature. In a validation cohort using the identified signature, we found an area under the curve (AUC) of 0.77 for CLAD LTRs. Targeted proteomic analyses revealed a predominant Type‐1 profile with detection of IFN‐γ, TNF‐α, and IL‐1β as dominant CLAD cytokines, correlating with the airway transcriptome. The airway transcriptome provides novel insights into CLAD immunopathogenesis and biomarkers that may impact diagnosis of CLAD.
This cross‐sectional analysis of transbronchial brush samples from lung transplant recipients identifies a transcriptomic signature marked by type‐1 immunity in recipients with chronic lung allograft dysfunction compared to stable controls.
Part of the process of deriving and refining the CARE (communication, accountability, respect, empowerment) focus group's potentially better practices (PBPs) for multidisciplinary teamwork was to ...evaluate and experience the PBPs through implementation.
The 4 neonatal intensive care units (NICUs) in the CARE focus group each worked with implementation of the PBPs. The choice of initial PBP and method of implementation was left up to each NICU's core team.
The experience of each of the PBPs that is reported was selected from only 1 of the NICUs. These are summarized and described in a plan-do-study-act type of format.
There was no ideal PBP with which to start. The intertwined nature of all of the PBPs provided additional opportunities to implement other PBPs. A change seemed to be a matter first of vocabulary, then of tentative acceptance, followed by gradual integration into the culture. Change was facilitated when there was acknowledgment of a need to do things differently by the NICU leadership. Although the validity of the PBPs and their importance in cultural change have yet to be confirmed, once there was a persisting intent to change, the makeup of the NICU culture moved to embrace change as part of its culture.
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