Cerebellar and Extracerebellar Involvement in Mouse Eyeblink Conditioning: the ACDC Model

Over the past decade the advent of mouse transgenics has generated new perspectives on the study of cerebellar molecular mechanisms that are essential for eyeblink conditioning. However, it also appears that results from eyeblink conditioning experiments done in mice differ in some aspects from results previously obtained in other mammals. In this review article we will, based on studies using (cell-specific) mouse mutants and region-specific lesions, re-examine the general eyeblink behavior in mice and the neuro-anatomical circuits that might contribute to the different peaks in the conditioned eyeblink trace. We conclude that the learning process in mice has at least two stages: An early stage, which includes short-latency responses that are at least partly controlled by extracerebellar structures such as the amygdala, and a later stage, which is represented by well-timed conditioned responses that are mainly controlled by the pontocerebellar and olivocerebellar systems. We refer to this overall concept as the Amygdala-Cerebellum-Dynamic-Conditioning Model (ACDC model)

Accessible and reliable neurometric testing in humans using a smartphone platform

Tests of human brain circuit function typically require fixed equipment in lab environments. We have developed a smartphone-based platform for neurometric testing. This platform, which uses AI models like computer vision, is optimized for at-home use and produces reproducible, robust results on a battery of tests, including eyeblink conditioning, prepulse inhibition of acoustic startle response, and startle habituation. This approach provides a scalable, universal resource for quantitative assays of central nervous system function.</p

New cut-off values for ferritin and soluble transferrin receptor for the assessment of iron deficiency in children in a high infection pressure area

Background: Due to the potential risk of iron supplementation in iron replete children, it is important to properly identify children who may require iron supplementation. However, assessment of the iron status has proven to be difficult, especially in children living in areas with high infection pressure (including malaria). Aims and Methods: Biochemical iron markers were compared to bone marrow iron findings in 381 Malawian children with severe anaemia. Results: Soluble transferrin receptor/log ferritin (TfR-F index), using a cut-off of 5.6, best predicted bone marrow iron stores deficiency (sensitivity 74%, specificity 73%, accuracy 73%). In order to improve the diagnostic accuracy of ferritin or sTfR as a stand-alone marker, the normal cut-off value needed to be increased by 810% and 83% respectively. Mean cell haemoglobin concentration (MCHC), using a cut-off of 32.1 g/dl, had a sensitivity of 67% and specificity of 64% for detecting iron stores deficiency. Conclusion: TfR-F index incorporated the high sensitivity of sTfR, a proxy for cellular iron need, and the high specificity of ferritin, a proxy for iron stores. In areas with a high infection pressure, the TfR-F index best predicted iron deficiency. However, in settings where diagnostic tests are limited, MCHC may be an acceptable alternative screening test

Pharmacological treatment of depression in people with a primary brain tumour

Background This is the second updated version of the Cochrane Review published in Issue 3, 2010 and first updated in Issue 5, 2013. People with a primary brain tumour oGen experience depression, for which drug treatment may be prescribed. However, they are also at high risk of epileptic seizures, cognitive impairment, and fatigue, all of which are potential adverse side effects of antidepressants. The benefit, or harm, of pharmacological treatment of depression in people with a primary brain tumour is unclear. Objectives To assess the benefits and harms of pharmacological treatment of depression in people with a primary brain tumour. Search methods We updated the search to include CENTRAL, MEDLINE, Embase, and PsycINFO to September 2019. As in the original review, we also handsearched Neuro-Oncology, Journal of Neuro-Oncology, Journal of Neurology, Neurosurgery and Psychiatry, and Journal of ClinicalOncology: for the current update we handsearched the latest three years of articles from these journals (up to November 2019). Selection criteria We searched for all randomised controlled trials (RCTs), controlled clinical trials, cohort studies, and case-control studies of any pharmacological treatment of depression in people with a histologically diagnosed primary brain tumour. Data collection and analysis No studies met the inclusion criteria. Main results We found no eligible studies evaluating the benefits of any pharmacological treatment of depression in people with a primary brain tumour. Authors' conclusions We identified no high-quality studies that investigated the value of pharmacological treatment of depression in people with a primary brain tumour. RCTs and detailed prospective studies are required to inform the effective pharmacological treatment of this common and important complication of brain tumours. Since the last version of this review none of the related new literature has provided additional information to change these conclusions

Improved method for assessing iron stores in the bone marrow

Background: Bone marrow iron microscopy has been the "gold standard'' method of assessing iron deficiency. However, the commonly used method of grading marrow iron remains highly subjective. Aim: To improve the bone marrow grading method by developing a detailed protocol that assesses iron in fragments, in macrophages around fragments and in erythroblasts. Methods: A descriptive study of marrow aspirates of 303 children (aged 6-60 months) with severe anaemia and 22 controls (children undergoing elective surgery) was conducted at hospitals in southern Malawi (2002-04). Results: Using an intensive marrow iron grading method, 22% and 39% of cases and controls had deficient iron stores, and 40% and 46% had functional iron deficiency, respectively. Further evaluation of the iron status classification by the intensive method showed that functional iron deficiency was associated with significantly increased C-reactive protein concentrations (126.7 (85.6) mg/l), and iron stores deficiency with significantly increased soluble transferrin receptor concentrations (21.7 (12.5) mg/ml). Conclusions: Iron assessment can be greatly improved by a more intense marrow examination. This provides a useful iron status classification which is of particular importance in areas where there is a high rate of inflammatory conditions

Parent–adolescent interaction quality and adolescent affect: An experience sampling study on effect heterogeneity

Person–environment interactions might ultimately drive longer term development. This experience sampling study (Data collection: 2019/20 the Netherlands) assessed short-term linkages between parent–adolescent interaction quality and affect during 2281 interactions of 124 adolescents (Mage = 15.80, SDage= 1.69, 59% girls, 92% Dutch, Education: 25% low, 31% middle, 35% high, 9% other). Adolescents reported on parent–adolescent interaction quality (i.e., warmth and conflict) and momentary positive and negative affect five to six times a day, for 14 days. Preregistered dynamic structural equation models (DSEM) revealed within-family associations between parent–adolescent interaction quality and adolescent affect (concurrently: r = −.22 to.39; lagged effects: ß = −.17 to.15). These effects varied significantly between families. These findings stress the need for more person-specific research on parenting processes

Universal ingredients to parenting teens: parental warmth and autonomy support promote adolescent well-being in most families

Even though each adolescent is unique, some ingredients for development may still be universal. According to Self-Determination Theory, every adolescent’s well-being should benefit when parents provide warmth and autonomy. To rigorously test this idea that each family has similar mechanisms, we followed 159 Dutch parent-adolescent dyads (parent: Mage = 45.34, 79% mothers; adolescent: Mage = 13.31, 62% female) for more than three months, and collected 100 consecutive daily reports of parental warmth, autonomy support, positive and negative affect. Positive effects of parental warmth and autonomy support upon well-being were found in 91–98% of the families. Preregistered analysis of 14,546 daily reports confirmed that effects of parenting differed in strength (i.e., some adolescents benefited more than others), but were universal in their direction (i.e., in fewer than 1% of families effects were in an unexpected direction). Albeit stronger with child-reported parenting, similar patterns were found with parent-reports. Adolescents who benefited most from need-supportive parenting in daily life were characterized by higher overall sensitivity to environmental influences. Whereas recent work suggests that each child and each family have unique developmental mechanisms, this study suggests that need-supportive parenting promotes adolescent well-being in most families

Unmet needs and wish for support of family caregivers of primary brain tumor patients

Background Most primary brain tumor patients rely on family caregivers for support. Caregiving can be rewarding, but also leads to significant burden from unmet needs. We aimed to: (1) identify and characterize caregivers’ unmet needs; (2) determine associations between unmet needs and wish for support; (3) evaluate acceptability of the Caregiver Needs Screen (CNS) and perceived feasibility in clinical practice. Methods Family caregivers of primary brain tumor patients were recruited from outpatient clinics and asked to complete an adapted version of the CNS consisting of 33 common issues caregivers report (item scale 0–10), and the wish for support (yes/no). Participants ranked acceptability and feasibility (item scale 0–7; higher scores being positive) of the adapted CNS. Descriptive and non-parametric correlational analyses were applied. Results Caregivers (N = 71) reported 1–33 unmet caregiving needs (M = 17.20, sd = 7.98) but did not always wish for support (range 0–28, M = 5.82, sd = 6.96). A weak correlation was found between total number of unmet needs and wish for support (r = 0.296, P = .014). Most distressing items were patients’ changes in memory/concentration (M = 5.75, sd = 3.29), patients’ fatigue (M = 5.58, sd = 3.43), and signs of disease progression (M = 5.23, sd = 3.15).Caregivers most often wished support with recognizing disease progression (N = 24), and least often with managing spiritual issues (N = 0). Caregivers evaluated acceptability and feasibility of the CNS tool positively (mean scores ranged 4.2–6.2). Conclusions Family caregivers experience distress resulting from many neuro-oncology specific needs, but this is not directly related to wish for support. Family caregiver needs screening could be useful to tailor support to suit their preferences in clinical practice

Communication in the context of glioblastoma treatment: A qualitative study of what matters most to patients, caregivers and health care professionals

Background: Patients with glioblastoma have a poor prognosis and treatment is palliative in nature from diagnosis. It is therefore critical that the benefits and burdens of treatments are clearly discussed with patients and caregivers. Aim: To explore experiences and preferences around glioblastoma treatment communication in patients, family caregivers and healthcare professionals. Design: Qualitative design. A thematic analysis of semi-structured interviews. Setting/participants: A total of 15 adult patients with glioblastoma, 13 caregivers and 5 healthcare professionals were recruited from Leeds Teaching Hospitals NHS Trust. Results: Four themes were identified: (1) Communication practice and preferences. Risks and side-effects of anti-tumour treatments were explained clearly, with information layered and repeated. Treatment was often understood to be ‘the only option’. Understanding the impact of side-effects could be enhanced, alongside information about support services. (2) What matters most. Patients/caregivers valued being well-supported by a trusted treatment team, feeling involved, having control and quality of life. Healthcare professionals similarly highlighted trust, maintaining independence and emotional support as key. (3) Decision-making. With limited treatment options, trust and control are crucial in decision-making. Patients ultimately prefer to follow healthcare professional advice but want to be involved, consider alternatives and voice what matters to them. (4) Impact of COVID-19. During the pandemic, greater efforts to maintain good communication were necessary. Negative impacts of COVID-19 were limited, caregivers appeared most disadvantaged by pandemic-related restrictions. Conclusions: In glioblastoma treatment communication, where prognosis is poor and treatment will not result in cure, building trusting relationships, maintaining a sense of control and being well-informed are identified as critical