Docosahexaenoic acid for reading, working memory and behavior in UK children aged 7-9: A randomized controlled trial for replication (the DOLAB II study)

Background: Omega-3 fatty acids are central to brain-development of children. Evidence from clinical trials and systematic reviews demonstrates the potential of long-chain Omega-3 supplementation for learning and behavior. However, findings are inconclusive and in need of robust replication studies since such work is lacking. Objectives: Replication of the 2012 DOLAB 1 study findings that a dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA) had beneficial effects on the reading, working memory, and behavior of healthy schoolchildren. Design: Parallel group, fixed-dose, randomized (minimization, 30% random element), double-blind, placebo-controlled trial (RCT). Setting: Mainstream primary schools (n = 84) from five counties in the UK in 2012–2015. Participants: Healthy children aged 7–9 underperforming in reading (<20th centile). 1230 invited, 376 met study criteria. Intervention: 600 mg/day DHA (from algal oil), placebo: taste/color matched corn/soybean oil; for 16 weeks. Main outcome measures: Age-standardized measures of reading, working memory, and behavior, parent-rated and as secondary outcome teacher-rated. Results: 376 children were randomized. Reading, working memory, and behavior change scores showed no consistent differences between intervention and placebo group. Some behavioral subscales showed minor group differences. Conclusions: This RCT did not replicate results of the earlier DOLAB 1 study on the effectiveness of nutritional supplementation with DHA for learning and behavior. Possible reasons are discussed, particularly regarding the replication of complex interventions. Trial registration and protocol: www.controlled-trials.com (ISRCTN48803273) and protocols.io (https://dx.doi.org/10.17504/protocols.io.k8kczuw)

Regular exercise during haemodialysis promotes an anti-inflammatory leucocyte profile

Background Cardiovascular disease (CVD) is the most common cause of mortality in haemodialysis (HD) patients and is highly predicted by markers of chronic inflammation. Regular exercise may have beneficial anti-inflammatory effects, but this is unclear in HD patients. This study assessed the effect of regular intradialytic exercise on soluble inflammatory factors and inflammatory leukocyte phenotypes. Methods Twenty-two HD patients from a centre where intradialytic cycling was offered thrice-weekly and 16 HD patients receiving usual care volunteered. Exercising patients aimed to cycle for 30 min at RPE of “somewhat hard”. Baseline characteristic were compared with 16 healthy age-matched individuals. Physical function, soluble inflammatory markers and leukocyte phenotypes were assessed again after 6 months of regular exercise. Results Patients were less active than their healthy counterparts and had significant elevations in measures of inflammation (IL-6, CRP, TNF-α, intermediate and non-classical monocytes; all P<0.001). Six months of regular intradialytic exercise improved physical function (sit-to-stand 60). After 6 months the proportion of intermediate monocytes in the exercising patients reduced compared to non-exercisers (7.58±1.68 to 6.38±1.81% vs. 6.86±1.45 to 7.88±1.66%; P<0.01). Numbers (but not proportion) of regulatory T cells decreased in the non-exercising patients only (P<0.05). Training had no significant effect on circulating IL-6, CRP or TNF-α concentrations. Conclusions These findings suggest regular intradialytic exercise is associated with an anti-inflammatory effect at a circulating cellular level but not in circulating cytokines. This may be protective against the increased risk of CVD and mortality that is associated with chronic inflammation and elevated numbers of intermediate monocytes

Isolation of human intrahepatic leukocytes for phenotypic and functional characterization by flow cytometry

With the growing appreciation of tissue-resident immunity, studying tissue-specific immune cells contributing to both homeostasis and disease is imperative. Here, we provide a protocol for the isolation of human intrahepatic leukocytes (IHL) maximizing viability, purity, and yield. Our protocol is scalable by tissue weight, allowing for reproducible and efficient IHL liberation suitable for functional characterization, cell isolation, and profiling by flow (or mass) cytometry. Furthermore, we provide a "guide" to determine an expected IHL yield per gram of tissue processed. For complete details on the use and execution of this protocol, please refer to Stegmann et al. (2016), Pallett et al. (2017), Easom et al. (2018), Swadling et al. (2020), Pallett et al. (2020), and Zakeri et al. (2022)

Implementing a theory-based intradialytic exercise programme in practice: a quality improvement project

Background Research evidence outlines the benefits of intradialytic exercise (IDE), yet implementation into practice has been slow, ostensibly due to lack of patient and staff engagement. The aim of this quality improvement project was to improve patient outcomes via the introduction of an IDE programme; evaluate patient uptake, sustainability and enhance the engagement of routine haemodialysis (HD) staff with the delivery of the IDE programme. Methods We developed and refined an IDE programme, including interventions designed to increase patient and staff engagement that were based upon the Theoretical Domains Framework, using a series of ‘Plan, Do, Study, Act’ cycles. The programme was introduced at two UK NHS HD units. Process measures included patient uptake, withdrawals, adherence and HD staff involvement. Outcomes measures were patient-reported functional capacity, anxiety, depression and symptomology. All measures were collected over 12 months. Results 95 patients enrolled in the IDE programme. 64 (75%) were still participating at three months, dropping to 41 (48%) at 12 months. Adherence was high (78%) at three months, dropping to 63% by 12 months. Provision of IDE by HD staff accounted for a mean of 2 (5%) sessions per three-month time point. Patients displayed significant improvements in functional ability (p=0.01), and reduction in depression (p=0.02) over 12 months, but effects seen were limited to those who completed the programme. Conclusions A theory-based IDE programme is feasible and leads to improvement in functional capacity and depression. Sustaining IDE over time is marred by high levels of patient withdrawal from the programme. Significant change at an organisational level is required to enhance sustainability by increasing HD staff engagement or access to exercise professional support

A Comparison of Dietary Intake Between Individuals Undergoing Maintenance Hemodialysis in the United Kingdom and China

OBJECTIVE: Protein-energy wasting is highly prevalent in people with end-stage kidney disease receiving regular hemodialysis. Currently, it is unclear what the optimal nutritional recommendations are, which is further complicated by differences in dietary patterns between countries. The aim of the study was to understand and compare dietary intake between individuals receiving hemodialysis in Leicester, UK and Nantong, China. METHODS: The study assessed 40 UK and 44 Chinese participants' dietary intake over a period of 14 days using 24-hour diet recall interviews. Nutritional blood parameters were obtained from medical records. Food consumed by participants in the UK and China was analyzed using the Nutritics and Nutrition calculator to quantify nutritional intake. RESULTS: Energy and protein intake were comparable between UK and Chinese participants, but with both below the recommended daily intake. Potassium intake was higher in UK participants compared to Chinese participants (2,115 [888] versus 1,159 [861] mg/d; P < .001), as was calcium (618 [257] versus 360 [312] mg/d; P < .001) and phosphate intake (927 [485] versus 697 [434] mg/d; P = .007). Vitamin C intake was lower in UK participants compared to their Chinese counterparts (39 [51] versus 64 [42] mg/d; P = .024). Data are reported here as median (interquartile range). CONCLUSION: Both UK and Chinese hemodialysis participants have insufficient protein and energy in their diet. New strategies are required to increase protein and energy intakes. All participants had inadequate daily intake of vitamins C and D; there may well be a role in the oral supplementation of these vitamins, and further studies are urgently needed

Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

Effective control of SARS-CoV-2 infection on primary exposure may reveal correlates of protective immunity to future variants, but we lack insights into immune responses before or at the time virus is first detected. We use blood transcriptomics, multiparameter flow cytometry, and T cell receptor (TCR) sequencing spanning the time of incident non-severe infection in unvaccinated virus-naive individuals to identify rapid type 1 interferon (IFN) responses common to other acute respiratory viruses and cell proliferation responses that discriminate SARS-CoV-2 from other viruses. These peak by the time the virus is first detected and sometimes precede virus detection. Cell proliferation is most evident in CD8 T cells and associated with specific expansion of SARS-CoV-2-reactive TCRs, in contrast to virus-specific antibodies, which lag by 1–2 weeks. Our data support a protective role for early type 1 IFN and CD8 T cell responses, with implications for development of universal T cell vaccines

Patients with low back pain differ from those who also have leg pain or signs of nerve root involvement - A cross-sectional study

Background: Leg pain associated with low back pain (LBP) is recognized as a risk factor for a poor prognosis, and is included as a component in most LBP classification systems. The location of leg pain relative to the knee and the presence of a positive straight leg raise test have been suggested to have clinical implications. To understand differences between such leg pain subgroups, and whether differences include potentially modifiable characteristics, the purpose of this paper was to describe characteristics of patients classified into the Quebec Task Force (QTF) subgroups of: 1) LBP only, 2) LBP and pain above the knee, 3) LBP and pain below the knee, and 4) LBP and signs of nerve root involvement. Methods. Analysis of routine clinical data from an outpatient department. Based on patient reported data and clinical findings, patients were allocated to the QTF subgroups and described according to the domains of pain, activity limitation, work participation, psychology, general health and clinical examination findings. Results: A total of 2,673 patients aged 18-95 years (median 47) who were referred for assessment of LBP were included. Increasing severity was consistently observed across the subgroups from LBP only to LBP with signs of nerve root involvement although subgroup differences were small. LBP patients with leg pain differed from those with LBP only on a wide variety of parameters, and patients with signs of nerve root involvement had a more severe profile on almost all measures compared with other patients with back-related leg pain. Conclusion: LBP patients with pain referral to the legs were more severely affected than those with local LBP, and patients with signs of nerve root involvement were the ones most severily affected. These findings underpin the concurrent validity of the Quebec Task Force Classification. However, the small size of many between-subgroup differences amid the large variability in this sample of cross-sectional data also underlines that the heterogeneity of patients with LBP is more complex than that which can be explained by leg pain patterns alone. The implications of the observed differences also require investigation in longitudinal studies

IL-2(high) tissue-resident T cells in the human liver: Sentinels for hepatotropic infection

The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+)). These tissue-resident memory T cells (TRM) are preferentially expanded in patients with partial immune control of HBV infection and can remain in the liver after the resolution of infection, including compartmentalized responses against epitopes within all major HBV proteins. Sequential IL-15 or antigen exposure followed by TGFβ induces liver-adapted TRM, including their signature high expression of exhaustion markers PD-1 and CD39. We suggest that these inhibitory molecules, together with paradoxically robust, rapid, cell-autonomous IL-2 and IFNγ production, equip liver CD8 TRM to survive while exerting local noncytolytic hepatic immunosurveillance

Sexual and reproductive health and human rights of women living with HIV

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/1/jia20834-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/2/jia20834.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/3/jia20834-sup-0002.pd