My Kidney Is Fine, Can't You Cystatin C?

Background: Independent of age, sex, and body composition, individuals of African American race and individuals with high muscle mass have elevated serum creatinine (sCr) levels on average that may result in overestimation of chronic kidney disease (CKD). We present a misdiagnosed case of CKD based on sCr levels, illustrating the utility of cystatin C (CysC) confirmation testing to answer the question: Can confirmation screening of kidney function with CysC in African American patients and patients with high muscle mass reduce the misdiagnosis of CKD? Case Presentation: A 35-year-old African American man with a history of well-controlled HIV was found to have consistently elevated creatinine (Cr). We diagnosed CKD stage 3A based on the estimated glomerular filtration rate (eGFR). Further evaluation showed isolated elevation of sCr with unremarkable urinalysis and other laboratory tests. sCr elevation predated diagnosis and HIV treatment. A CysC-based eGFR (eGFRcys) test confirmed the absence of CKD. Conclusions: The 2009 CKD Epidemiology Collaboration calculation of eGFR based on sCr concentration uses age, sex, and race, with an updated recommendation in 2021 to exclude race. Both equations are less accurate in African American patients, individuals taking medications that interfere with sCr secretion and assay, and patients taking creatine supplements or high protein intake. These clinical scenarios decrease sCr-based eGFR (eGFRCr) but do not change measured eGFR or eGFRCys. Using sCr and serum cystatin C (eGFRCr-Cys) yields better concordance to measured eGFR across all races than does eGFR estimation based on Cr alone. Confirmation with CysC can avoid misdiagnosis, incorrect dosing of drugs, and inaccurate representation of the fitness for duty.

Review of standard paediatric neuroradiology MRI protocols from 12 UK tertiary paediatric hospitals: is there much variation between centres?

AIM: To investigate how magnetic resonance imaging (MRI) examinations are protocolled in tertiary paediatric neuroradiology centres around the UK for some of the more common presentations encountered in paediatric neuroradiology, and to identify any variations of note. MATERIALS AND METHODS: All 19 UK tertiary paediatric neuroradiology centres registered with the British Society of Neuroradiologists-Paediatric Group were contacted and asked if they could provide a copy of their standard MRI protocols. Twelve responded (63%) and 10 of the more common presentations were selected and the standard acquired sequences obtained at each participating centre were compared. Where available the collated protocols were also compared against current published guidance. RESULTS: The basic sequences carried out by centres around the UK are similar; however, there are lots of variations overall. The only standardised protocol currently being implemented nationally in paediatric imaging is that for brain tumours. Otherwise, chosen protocols are generally dependent on the preferences and technical capabilities of individual centres. Suggested published protocols also exist for non-accidental injury (NAI), multiple sclerosis, epilepsy, and head and neck imaging. CONCLUSIONS: The differences in MRI protocolling depend in part on technical capabilities and in part on the experience and preferences of the paediatric neuroradiologists at each centre. For most presentations, there is no consensus as to what constitutes the perfect protocol. The present results will be useful for specialist centres who may wish to review their current protocols, and for more generalist centres to use as a reference to guide their MRI protocolling.

Locked down and divided: political orientation moderates the effects of considering a future lockdown.

To slow the spread of the COVID-19 virus, some U.S. State governments restricted public activity by implementing lockdowns. The possibility remains that lockdowns may need to be implemented in the future, whether to combat novel strains of COVID-19 or entirely different viruses. The present experiment tested whether thinking about a future lockdown affects people's attitudes toward institutions. We found that conservative participants who thought about a future lockdown reported less intention to adhere to the Centers for Disease Control and Prevention (CDC) guidelines and less trust in the government compared to conservative participants in a control condition. We also found that liberal participants who thought about a future lockdown reported more trust in the government and the CDC, compared to liberal participants in a control condition. These findings suggest that merely considering a future lockdown affects people's intended adherence and institutional trust. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-04208-2.

Evaluation of the Prevalence of Punctate White Matter Lesions in a Healthy Volunteer Neonatal Population.

Hypoxic-ischemic injury is the most common cause of neonatal encephalopathy. T1-weighted punctate white matter lesions have been described in hypoxic-ischemic injury. We have reviewed a healthy volunteer neonatal population to assess the prevalence of punctate white matter lesions in neonates with no clinical signs of hypoxic-ischemic injury. Fifty-two subjects were scanned on a neonatal-specific 3T MR imaging scanner. Twelve patients were excluded due to the lack of T1-weighted imaging, leaving a total of 40 patients (35 term, 5 preterm) assessed in the study. One had a solitary T1-punctate white matter lesion. We concluded that solitary punctate white matter lesions have a low prevalence in healthy neonates.

Optimising Medications for Patients With Cancer and Multimorbidity: The Case for Deprescribing.

The majority of patients diagnosed with cancer are aged over 65 years and have two or more chronic conditions in addition to cancer and the risk of chronic conditions increases further after cancer. The presence of multimorbidity adds complexity to care, as patients' goals of care and the focus of treatment can change with a diagnosis of cancer. Multimorbidity is frequently associated with polypharmacy, the use of potentially inappropriate medications, the presence of adverse drug reactions and potential drug-drug interactions: all of which impact on health outcomes and the cost of care. Consequently, it is vital that a systematic approach is taken to regularly review cancer patients' medication regimens to ensure that they support an optimal balance of benefits with acceptable levels of harm. Several patient and clinician resources are presented to guide the process of medication review and deprescribing.

Tissue magnetic susceptibility mapping as a marker of tau pathology in Alzheimer's disease.

Alzheimer's disease is connected to a number of other neurodegenerative conditions, known collectively as 'tauopathies', by the presence of aggregated tau protein in the brain. Neuroinflammation and oxidative stress in AD are associated with tau pathology and both the breakdown of axonal sheaths in white matter tracts and excess iron accumulation grey matter brain regions. Despite the identification of myelin and iron concentration as major sources of contrast in quantitative susceptibility maps of the brain, the sensitivity of this technique to tau pathology has yet to be explored. In this study, we perform Quantitative Susceptibility Mapping (QSM) and T2* mapping in the rTg4510, a mouse model of tauopathy, both in vivo and ex vivo. Significant correlations were observed between histological measures of myelin content and both mean regional magnetic susceptibility and T2* values. These results suggest that magnetic susceptibility is sensitive to tissue myelin concentrations across different regions of the brain. Differences in magnetic susceptibility were detected in the corpus callosum, striatum, hippocampus and thalamus of the rTg4510 mice relative to wild type controls. The concentration of neurofibrillary tangles was found to be low to intermediate in these brain regions indicating that QSM may be a useful biomarker for early stage detection of tau pathology in neurodegenerative diseases.

Emotional awareness and expression training improves irritable bowel syndrome: A randomized controlled trial.

BACKGROUND: Current clinical guidelines identify several psychological treatments for irritable bowel syndrome (IBS). IBS patients, however, have elevated trauma, life stress, relationship conflicts, and emotional avoidance, which few therapies directly target. We tested the effects of emotional awareness and expression training (EAET) compared to an evidence-based comparison condition-relaxation training-and a waitlist control condition. METHODS: Adults with IBS (N=106; 80% female, Mean age=36 years) were randomized to EAET, relaxation training, or waitlist control. Both EAET and relaxation training were administered in three, weekly, 50-minute, individual sessions. All patients completed the IBS Symptom Severity Scale (primary outcome), IBS Quality of Life, and Brief Symptom Inventory (anxiety, depressive, and hostility symptoms) at pretreatment and at 2 weeks posttreatment and 10 weeks follow-up (primary endpoint). KEY RESULTS: Compared to waitlist controls, EAET, but not relaxation training, significantly reduced IBS symptom severity at 10-week follow-up. Both EAET and relaxation training improved quality of life at follow-up. Finally, EAET did not reduce psychological symptoms, whereas relaxation training reduced depressive symptoms at follow-up (and anxiety symptoms at posttreatment). CONCLUSIONS & INFERENCES: Brief emotional awareness and expression training that targeted trauma and emotional conflicts reduced somatic symptoms and improved quality of life in patients with IBS. This emotion-focused approach may be considered an additional treatment option for IBS, although research should compare EAET to a full cognitive-behavioral protocol and determine which patients are best suited for each approach. Registered at clinicaltrials.gov (NCT01886027).

Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer's disease.

Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer's disease, and related neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer's disease.

In vivo imaging of tau pathology using multi-parametric quantitative MRI.

As the number of people diagnosed with Alzheimer's disease (AD) reaches epidemic proportions, there is an urgent need to develop effective treatment strategies to tackle the social and economic costs of this fatal condition. Dozens of candidate therapeutics are currently being tested in clinical trials, and compounds targeting the aberrant accumulation of tau proteins into neurofibrillary tangles (NFTs) are the focus of substantial current interest. Reliable, translatable biomarkers sensitive to both tau pathology and its modulation by treatment along with animal models that faithfully reflect aspects of the human disease are urgently required. Magnetic resonance imaging (MRI) is well established as a valuable tool for monitoring the structural brain changes that accompany AD progression. However the descent into dementia is not defined by macroscopic brain matter loss alone: non-invasive imaging measurements sensitive to protein accumulation, white matter integrity and cerebral haemodynamics probe distinct aspects of AD pathophysiology and may serve as superior biomarkers for assessing drug efficacy. Here we employ a multi-parametric array of five translatable MRI techniques to characterise the in vivo pathophysiological phenotype of the rTg4510 mouse model of tauopathy (structural imaging, diffusion tensor imaging (DTI), arterial spin labelling (ASL), chemical exchange saturation transfer (CEST) and glucose CEST). Tau-induced pathological changes included grey matter atrophy, increased radial diffusivity in the white matter, decreased amide proton transfer and hyperperfusion. We demonstrate that the above markers unambiguously discriminate between the transgenic group and age-matched controls and provide a comprehensive profile of the multifaceted neuropathological processes underlying the rTg4510 model. Furthermore, we show that ASL and DTI techniques offer heightened sensitivity to processes believed to precede detectable structural changes and, as such, provides a platform for the study of disease mechanisms and therapeutic intervention.

Periodontitis and cardiovascular disease.

Periodontal medicine has been studied and reviewed extensively since its introduction to the dental fraternity. The association of periodontal disease with and its effects on the cardiovascular system are amongst the many topics explored. A summary of the research into these associations and the possible mechanisms of any relationship is presented. Although a link between these two chronic inflammatory diseases is evident, the very heterogeneity of the relevant studies has not provided evidence sufficient to support an actual causal relationship. More stringent epidemiologic and intervention studies are required.

The benefits to communities and individuals of screening for active tuberculosis disease: a systematic review.

BACKGROUND: Screening for tuberculosis (TB) disease aims to improve early TB case detection. The ultimate goal is to improve outcomes for people with TB and to reduce Mycobacterium tuberculosis transmission in the community through improved case detection, reduction in diagnostic delays and early treatment. Before screening programmes are recommended, evidence is needed of individual and/or community-level benefits. METHODS: We conducted a systematic review of the literature to assess the evidence that screening for TB disease 1) initially increases the number of TB cases initiated on anti-tuberculosis treatment, 2) identifies cases earlier in the course of disease, 3) reduces mortality and morbidity, and 4) impacts on TB epidemiology. RESULTS: A total of 28 798 publications were identified by the search strategy: 27 087 were excluded on initial screening and 1749 on full text review, leaving 62 publications that addressed at least one of the study questions. Screening increases the number of cases found in the short term. In many settings, more than half of the prevalent TB cases in the community remain undiagnosed. Screening tends to find cases earlier and with less severe disease, but this may be attributed to case-finding studies using more sensitive diagnostic methods than routine programmes. Treatment outcomes among people identified through screening are similar to outcomes among those identified through passive case finding. Current studies provide insufficient evidence to show that active screening for TB disease impacts on TB epidemiology. CONCLUSION: Individual and community-level benefits from active screening for TB disease remain uncertain. So far, the benefits of earlier diagnosis on patient outcomes and transmission have not been established.

Magnetoelastic vibrational biomaterials for real-time monitoring and modulation of the host response.

Magnetoelastic (ME) biomaterials are ferromagnetic materials that physically deform when exposed to a magnetic field. This work describes the real-time control and monitoring capabilities of ME biomaterials in wound healing. Studies were conducted to demonstrate the capacity of the materials to monitor changes in protein adsorption and matrix stiffness. In vitro experiments demonstrated that ME biomaterials can monitor cell adhesion and growth in real-time, and a long-term in vivo study demonstrated their ability to monitor the host response (wound healing) to an implant and control local cell density and collagen matrix production at the soft tissue-implant interface. This approach represents a potentially self-aware and post-deployment activated biomaterial coating as a means to monitor an implant surface and provide an adjuvant therapy for implant fibrosis.