Maternal antenatal multiple micronutrient supplementation for long-term health benefits in children: a systematic review and meta-analysis

BACKGROUND: Multiple micronutrient supplementation for pregnant women reduces low birth weight and has been recommended in low- and middle-income countries (LMICs) to improve child survival, growth and health. We aimed to review the evidence from long-term follow-up studies of multiple micronutrient supplementation beginning in the later first or second trimester. METHODS: We searched systematically for follow-up reports from all trials in a 2015 Cochrane review of multiple micronutrient supplementation in pregnancy. The intervention comprised three or more micronutrients and the comparison group received iron (60 mg) and folic acid (400 μg), where possible. Median gestation of commencement varied from 9 to 23 weeks. Primary outcomes were offspring mortality, height, weight and head circumference, presented as unadjusted differences in means or proportions (intervention minus control). Secondary outcomes included other anthropometry, body composition, blood pressure, and cognitive and lung function. RESULTS: We found 20 follow-up reports from nine trials (including 88,057 women recruited), six of which used the UNIMMAP supplement designed to provide recommended daily allowances. The age of follow-up ranged from 0 to 9 years. Data for mortality estimates were available from all trials. Meta-analysis showed no difference in mortality (risk difference -0.05 per 1000 livebirths; 95 % CI, -5.25 to 5.15). Six trials investigated anthropometry and found no difference at follow-up in weight-for-age z score (0.02; 95 % CI, -0.03 to 0.07), height-for-age z score (0.01; 95 % CI, -0.04 to 0.06), or head circumference (0.11 cm; 95 % CI, -0.03 to 0.26). No differences were seen in body composition, blood pressure, or respiratory outcomes. No consistent differences were seen in cognitive function scores. CONCLUSIONS: There is currently no evidence that, compared with iron and folic acid supplementation, routine maternal antenatal multiple micronutrient supplementation improves childhood survival, growth, body composition, blood pressure, respiratory or cognitive outcomes

Characterising Australian memory clinics: current practice and service needs informing national service guidelines

Background: Memory clinics (MCs) play a key role in accurate and timely diagnoses and treatment of dementia and mild cognitive impairment. However, within Australia, there are little data available on current practices in MCs, which hinder international comparisons for best practice, harmonisation efforts and national coordination. Here, we aimed to characterise current service profiles of Australian MCs. Methods: The ‘Australian Dementia Network Survey of Expert Opinion on Best Practice and the Current Clinical Landscape’ was conducted between August-September 2020 as part of a larger-scale Delphi process deployed to develop national MC guidelines. In this study, we report on the subset of questions pertaining to current practice including wait-times and post-diagnostic care. Results: Responses were received from 100 health professionals representing 60 separate clinics (45 public, 11 private, and 4 university/research clinics). The majority of participants were from clinics in metropolitan areas (79%) and in general were from high socioeconomic areas. While wait-times varied, only 28.3% of clinics were able to offer an appointment within 1-2 weeks for urgent referrals, with significantly more private clinics (58.3%) compared to public clinics (19.5%) being able to do so. Wait-times were less than 8 weeks for 34.5% of non-urgent referrals. Only 20.0 and 30.9% of clinics provided cognitive interventions or post-diagnostic support respectively, with 7.3% offering home-based reablement programs, and only 12.7% offering access to group-based education. Metropolitan clinics utilised neuropsychological assessments for a broader range of cases and were more likely to offer clinical trials and access to research opportunities. Conclusions: In comparison to similar countries with comprehensive government-funded public healthcare systems (i.e., United Kingdom, Ireland and Canada), wait-times for Australian MCs are long, and post-diagnostic support or evidence-based strategies targeting cognition are not common practice. The timely and important results of this study highlight a need for Australian MCs to adopt a more holistic service of multidisciplinary assessment and post-diagnostic support, as well as the need for the number of Australian MCs to be increased to match the rising number of dementia cases

Interplay of quantum and classical fluctuations near quantum critical points

For a system near a quantum critical point (QCP), above its lower critical dimension $d_L$, there is in general a critical line of second order phase transitions that separates the broken symmetry phase at finite temperatures from the disordered phase. The phase transitions along this line are governed by thermal critical exponents that are different from those associated with the quantum critical point. We point out that, if the effective dimension of the QCP, $d_{eff}=d+z$ ($d$ is the Euclidean dimension of the system and $z$ the dynamic quantum critical exponent) is above its upper critical dimension $d_C$, there is an intermingle of classical (thermal) and quantum critical fluctuations near the QCP. This is due to the breakdown of the generalized scaling relation $\psi=\nu z$ between the shift exponent $\psi$ of the critical line and the crossover exponent $\nu z$, for $d+z>d_C$ by a \textit{dangerous irrelevant interaction}. This phenomenon has clear experimental consequences, like the suppression of the amplitude of classical critical fluctuations near the line of finite temperature phase transitions as the critical temperature is reduced approaching the QCP.Comment: 10 pages, 6 figures, to be published in Brazilian Journal of Physic

Factors Associated with Participation in a Multidomain Web-Based Dementia Prevention Trial: Evidence from Maintain Your Brain (MYB)

Background: The Maintain Your Brain (MYB) trial aims to prevent cognitive decline and dementia through multidomain, web-based risk-reduction. To facilitate translation, it is important to understand drivers of participation. Objective: To describe characteristics associated with participation in MYB. Methods: This was an observational ancillary study of MYB, a randomized controlled trial nested within the 45 and Up Study in New South Wales, Australia. We linked 45 and Up Study survey and MYB participation data. The study cohort comprised 45 and Up Study participants, aged 55-77 years at 1 January 2018, who were invited to participate in MYB. 45 and Up Study participant characteristics and subsequent MYB consent and participation were examined. Results: Of 98,836 invited, 13,882 (14%) consented to participate and 6,190 participated (6%). Adjusting for age and sex, a wide range of factors were related to participation. Higher educational attainment had the strongest relationship with increased MYB participation (university versus school non-completion; AdjOR = 5.15; 95% CI:4.70-5.64) and lower self-rated quality of life with reduced participation (Poor versus Excellent: AdjOR = 0.19; 95% CI:0.11-0.32). A family history of Alzheimer's disease was related to increased participation but most other dementia risk factors such as diabetes, obesity, stroke, high blood pressure, and current smoking were associated with reduced participation. Conclusion: Higher socio-economic status, particularly educational attainment, is strongly associated with engagement in online dementia prevention research. Increasing population awareness of dementia risk factors, and better understanding the participation barriers in at-risk groups, is necessary to ensure online interventions are optimally designed to promote maximum participation

Reduced coronary flow reserve in Anderson-Fabry disease measured by transthoracic Doppler echocardiography

Coronary flow reserve was assessed in a patient with Anderson-Fabry disease complicated by symmetric left ventricular hypertrophy. Coronary flow reserve was measurable in all three major coronary arteries providing an opportunity to compare regional coronary flow reserve from different vascular beds. In this patient all the three vascular beds supplied diffusely hypertrophied myocardium. Coronary flow disturbances in small intramyocardial perforating arteries were visible. The coronary flow reserve was reduced to a similar level (around to 2.0) in all three major arteries. In our patient with Anderson-Fabry disease, the coronary vasodilatation was blunted in a diffuse pattern corresponding to the myocardial hypertrophy distribution. In small intramyocardial arteries coronary flow was also disturbed. Accordingly, retrograde systolic flow and accelerated anterograde diastolic flow were documented

Overvaluation of shape and weight in adolescents with anorexia nervosa: does shape concern or weight concern matter more for treatment outcome?

BACKGROUND: Overvaluation of shape and weight is a key diagnostic feature of anorexia nervosa (AN); however, limited research has evaluated the clinical utility of differentiating between weight versus shape concerns. Understanding differences in these constructs may have important implications for AN treatment given the focus on weight regain. This study examined differences in treatment outcome between individuals whose primary concern was weight versus those whose primary concern was shape in a randomized controlled trial of treatment for adolescent AN. METHODS: Data were drawn from a two-site randomized controlled trial that compared family-based treatment and adolescent focused therapy for AN. Chi-square tests and logistic regression analyses were conducted. RESULTS: Thirty percent of participants presented with primary weight concern (n = 36; defined as endorsing higher Eating Disorder Examination (EDE) Weight Concern than Shape Concern subscale scores); 60 % presented with primary shape concern (n = 72; defined as endorsing higher EDE Shape Concern than Weight Concern scores). There were no significant differences between the two groups in remission status at the end of treatment. Treatment did not moderate the effect of group status on achieving remission. CONCLUSIONS: Results suggest that treatment outcomes are comparable between adolescents who enter treatment for AN with greater weight concerns and those who enter treatment with greater shape concerns. Therefore, treatment need not be adjusted based on primary weight or primary shape concerns

Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study.

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD

Diagnostic relevance of spatial orientation for vascular dementia: A case study

Background: Spatial orientation is emerging as an early and reliable cognitive biomarker of Alzheimer’s disease (AD) pathophysiology. However, no evidence exists as to whether spatial orientation is also affected in vascular dementia (VaD). Objective: To examine allocentric (map-based) and egocentric (viewpoint-based) spatial orientation in an early stage VaD case. Methods: A spatial test battery was administered following clinical and neuropsychological cognitive evaluation. Results: Despite the patient’s complaints, little evidence of episodic memory deficits were detected when cueing was provided to overcome executive dysfunction. Similarly, medial temporal lobe-mediated allocentric orientation was intact. By contrast, medial parietal-mediated egocentric orientation was impaired, despite normal performance on standard visuospatial tasks. Conclusion: To our knowledge, this is the first in-depth investigation of spatial orientation deficits in VaD. Isolated egocentric deficits were observed. This differs from AD orientation deficits which encompass both allocentric and egocentric orientation deficits. A combination of egocentric orientation and executive function tests could serve as a promising cognitive marker for VaD pathophysiology

SUMOylation of DRIL1 Directs Its Transcriptional Activity Towards Leukocyte Lineage-Specific Genes

DRIL1 is an ARID family transcription factor that can immortalize primary mouse fibroblasts, bypass RASV12-induced cellular senescence and collaborate with RASV12 or MYC in mediating oncogenic transformation. It also activates immunoglobulin heavy chain transcription and engages in heterodimer formation with E2F to stimulate E2F-dependent transcription. Little, however, is known about the regulation of DRIL1 activity. Recently, DRIL1 was found to interact with the SUMO-conjugating enzyme Ubc9, but the functional relevance of this association has not been assessed. Here, we show that DRIL1 is sumoylated both in vitro and in vivo at lysine 398. Moreover, we provide evidence that PIASy functions as a specific SUMO E3-ligase for DRIL1 and promotes its sumoylation both in vitro and in vivo. Furthermore, consistent with the subnuclear localization of PIASy in the Matrix-Associated Region (MAR), SUMO-modified DRIL1 species are found exclusively in the MAR fraction. This post-translational modification interferes neither with the subcellular localization nor the DNA-binding activity of the protein. In contrast, DRIL1 sumoylation impairs its interaction with E2F1 in vitro and modifies its transcriptional activity in vivo, driving transcription of subset of genes regulating leukocyte fate. Taken together, these results identify sumoylation as a novel post-translational modification of DRIL1 that represents an important mechanism for targeting and modulating DRIL1 transcriptional activity

Bilateral acute angle closure glaucoma as a presentation of isolated microspherophakia in an adult: case report

BACKGROUND: Bilateral simultaneous angle closure glaucoma is a rare entity. To our knowledge this is the first reported case of bilateral acute angle-closure glaucoma secondary to isolated microspherophakia in an adult. CASE PRESENTATION: A 45-year-old woman presented with bilateral acute angle closure glaucoma, with a patent iridotomy in one eye. Prolonged miotic use prior to presentation had worsened the pupillary block. The diagnosis was not initially suspected, and the patient was subjected to pars-plana lensectomy and anterior vitrectomy for a presumed ciliary block glaucoma. The small spherical lens was detected intraoperatively, and spherophakia was diagnosed in retrospect. She had no systemic features of any of the known conditions associated with spherophakia. Pars-plana lensectomy both eyes controlled the intraocular pressure successfully. CONCLUSION: This case demonstrates the importance of considering the diagnosis of isolated microspherophakia in any case of bilateral acute angle closure glaucoma. Lensectomy appears to be an effective first-line strategy for managing these patients