Aducanumab anti-amyloid immunotherapy induces sustained microglial and immune alterations

Aducanumab, an anti-amyloid immunotherapy for Alzheimer\u27s disease, efficiently reduces Aβ, though its plaque clearance mechanisms, long-term effects, and effects of discontinuation are not fully understood. We assessed the effect of aducanumab treatment and withdrawal on Aβ, neuritic dystrophy, astrocytes, and microglia in the APP/PS1 amyloid mouse model. We found that reductions in amyloid and neuritic dystrophy during acute treatment were accompanied by microglial and astrocytic activation, and microglial recruitment to plaques and adoption of an aducanumab-specific pro-phagocytic and pro-degradation transcriptomic signature, indicating a role for microglia in aducanumab-mediated Aβ clearance. Reductions in Aβ and dystrophy were sustained 15 but not 30 wk after discontinuation, and reaccumulation of plaques coincided with loss of the microglial aducanumab signature and failure of microglia to reactivate. This suggests that despite the initial benefit from treatment, microglia are unable to respond later to restrain plaque reaccumulation, making further studies on the effect of amyloid-directed immunotherapy withdrawal crucial for assessing long-term safety and efficacy

Mainstreaming Grassroots Level Adaptation and Building Climate Resilient Agriculture in SAT* Bangladesh

Global climate is likely to change further and faster over the coming decades, resulting in adverse impacts on ecosystems, peoples’ livelihood and economy. There are evidences that climate change has affected global weather patterns, disrupted climatic trends and has resulted in aggravated occurrences of climate related extreme events such as heavy rainfall, drought, flood, cyclone, storm surge, etc, claiming thousands of lives, destroying billions of dollars worth of properties and disrupting livelihoods of hundreds of millions of people

Shonjibon cash and counselling: a community-based cluster randomised controlled trial to measure the effectiveness of unconditional cash transfers and mobile behaviour change communications to reduce child undernutrition in rural Bangladesh.

BackgroundUndernutrition is strongly associated with poverty - levels of undernutrition are higher in poor countries than in better-off countries. Social protection especially cash transfer is increasingly recognized as an important strategy to accelerate progress in improving maternal and child nutrition. A critical method to improve nutrition knowledge and influence feeding practices is through behaviour change communication intervention. The Shonjibon Cash and Counselling study aims to assess the effectiveness of unconditional cash transfers combined with a mobile application on nutrition counselling and direct counselling through mobile phone in reducing the prevalence of stunting in children at 18 months.MethodThe study is a longitudinal cluster randomised controlled trial, with two parallel groups, and cluster assignment by groups of villages. The cohort of mother-child dyads will be followed-up over the intervention period of approximately 24 months, starting from recruitment to 18 months of the child's age. The study will take place in north-central Bangladesh. The primary trial outcome will be the percentage of stunted children at 18 m as measured in follow up assessments starting from birth. The secondary trial outcomes will include differences between treatment arms in (1) Mean birthweight, percentage with low birthweight and small for gestational age (2) Mean child length-for age, weight for age and weight-for-length Z scores (3) Prevalence of child wasting (4) Percentage of women exclusively breastfeeding and mean duration of exclusive breastfeeding (5) Percentage of children consuming > 4 food groups (6) Mean child intake of energy, protein, carbohydrate, fat and micronutrients (7) Percentage of women at risk of inadequate nutrient intakes in all three trimesters (8) Maternal weight gain (9) Household food security (10) Number of events for child suffering from diarrhoea, acute respiratory illness and fever (11) Average costs of mobile phone BCC and cash transfer, and benefit-cost ratio for primary and secondary outcomes.DiscussionThe proposed trial will provide high-level evidence of the efficacy and cost-effectiveness of mobile phone nutrition behavior change communication, combined with unconditional cash transfers in reducing child undernutrition in rural Bangladesh.Trial registrationThe study has been registered in the Australian New Zealand Clinical Trials Registry ( ACTRN12618001975280 )

Correlates of physical activity and sitting time in adults with type 2 diabetes attending primary health care in Oman

Abstract Background Despite evidence of the benefits of physical activity in the management of type 2 diabetes, it is poorly addressed in diabetes care. This study aimed to identify the prevalence and correlates of meeting ≥600MET-min/wk. (150 min/wk) of physical activity and sitting time in adults with type 2 diabetes in Oman. Approaches to encourage physical activity in diabetes care were explored. Methods A cross-sectional study using the Global Physical Activity Questionnaire was conducted in 17 randomly selected primary health centres in Muscat. Clinical data including co-morbidities were extracted from the health information system. Questions on physical activity preferences and approaches were included. Patients were approached if they were ≥18 years, and had been registered in the diabetes clinic for >2 years. Results The questionnaire was completed by 305 people (females 57% and males 43%). Mean age (SD) was 57 (10.8) years and mean BMI (SD) was 31.0 (6.0) kg/m2. Duration of diabetes ranged from 2 to 25 (mean 7.6) years. Hypertension (71%) and dyslipidaemia (62%) were common comorbidities. Most (58.4%) had an HbA1c ≥7% indicating poor glycaemic control (55% in males vs 61% in females). Physical activity recommendations were met by 21.6% of the participants, mainly through leisure activities. Odds of meeting the recommendations were significantly higher in males (OR 4.8, 95% CI 2.5–9.1), individuals ≤57 years (OR 3.0, 95% CI 1.6–5.9), those at active self-reported stages of change for physical activity (OR 2.2, 95% CI 1.2–4.1) and those reporting no barriers to performing physical activity (OR 2.7, 95% CI 1.4–4.9). Median (25th, 75th percentiles) sitting time was 705 (600, 780) min/d. Older age (>57 years) was associated with longer sitting time (>705 min/d) (OR 2.8, 95% CI 1.7–4.6). Preferred methods to support physical activity in routine diabetes care were consultations (38%), structured physical activity sessions (13.4%) and referrals to physical activity facilities (5.6%) delivered by a variety of health care providers. Conclusions The results suggest that intervention strategies should take account of gender, age, opportunities within daily life to promote active behaviour and readiness to change. Offering physical activity consultations is of interest to this study population, thus development and evaluation of interventions are warranted

Characterization of complex networks: A survey of measurements

Each complex network (or class of networks) presents specific topological features which characterize its connectivity and highly influence the dynamics of processes executed on the network. The analysis, discrimination, and synthesis of complex networks therefore rely on the use of measurements capable of expressing the most relevant topological features. This article presents a survey of such measurements. It includes general considerations about complex network characterization, a brief review of the principal models, and the presentation of the main existing measurements. Important related issues covered in this work comprise the representation of the evolution of complex networks in terms of trajectories in several measurement spaces, the analysis of the correlations between some of the most traditional measurements, perturbation analysis, as well as the use of multivariate statistics for feature selection and network classification. Depending on the network and the analysis task one has in mind, a specific set of features may be chosen. It is hoped that the present survey will help the proper application and interpretation of measurements.Comment: A working manuscript with 78 pages, 32 figures. Suggestions of measurements for inclusion are welcomed by the author

The impact of health system governance and policy processes on health services in Iraqi Kurdistan

BACKGROUND: Relative to the amount of global attention and media coverage since the first and second Gulf Wars, very little has been published in the health services research literature regarding the state of health services in Iraq, and particularly on the semi-autonomous region of Kurdistan. Building on findings from a field visit, this paper describes the state of health services in Kurdistan, analyzes their underlying governance structures and policy processes, and their overall impact on the quality, accessibility and cost of the health system, while stressing the importance of reinvesting in public health and community-based primary care. DISCUSSION: Very little validated, research-based data exists relating to the state of population health and health services in Kurdistan. What little evidence exists, points to a region experiencing an epidemiological polarization, with different segments of the population experiencing rapidly-diverging rates of morbidity and mortality related to different etiological patterns of communicable, non-communicable, acute and chronic illness and disease. Simply put, the rural poor suffer from malnutrition and cholera, while the urban middle and upper classes deal with issues of obesity and Type 2 diabetes. The inequity is exacerbated by a poorly governed, fragmented, unregulated, specialized and heavily privatized system, that not only leads to poor quality of care and catastrophic health expenditures, but also threatens the economic and political stability of the region. There is an urgent need to revisit and clearly define the core values and goals of a future health system, and to develop an inclusive governance and policy framework for change, towards a more equitable and effective primary care-based health system, with attention to broader social determinants of health and salutogenesis. SUMMARY: This paper not only frames the situation in Kurdistan in terms of a human rights or special political issue of a minority population, but provides important generalizable lessons for other constituencies, highlighting the need for political action before effective public health policies can be implemented - as embodied by Rudolf Virchow, the father of European public health and pathology, in his famous quote "politics is nothing but medicine at a larger scale"

Metabolic response to subacute and subchronic iron overload in a rat model

One of the common causes of iron overload is excessive iron intake in cases of iron-poor anemia, where iron saccharate complex (ISC) is routinely used to optimize erythropoiesis. However, non-standardized ISC administration could entail the risk of iron overload. To induce iron overload, Wistar rats were intraperitoneally injected with subacute (0.2 mg kg−1) and subchronic (0.1 mg kg−1) overdoses of ISC for 2 and 4 weeks, respectively. Iron status was displayed by an increase in transferrin saturation (up to 332%) and serum and liver iron burden (up to 19.3 μmol L−1 and 13.2 μmol g−1 wet tissue, respectively) together with a drop in total and unsaturated iron binding capacities “TIBC, UIBC” as surrogate markers of transferrin activity. Iron-induced leukocytosis (up to 140%), along with the decline in serum transferrin markers (up to 43%), respectively, mark positive and negative acute phase reactions. Chemical stress was demonstrated by a significant rise (p > 0.05) in indices of the hemogram (erythrocytes, hemoglobin, hematocrit, leukocytes) and stress metabolites [corticosterone (CORT) and lactate]. Yet, potential causes of the unexpected decline in serum activities of ALT, AST and LDH (p > 0.05) might include decreased hepatocellular enzyme production and/or inhibition or reduction of the enzyme activities. The current findings highlight the toxic role of elevated serum and liver iron in initiating erythropoiesis and acute phase reactions, modifying iron status and animal organ function, changing energy metabolism and bringing about accelerated glycolysis and impaired lactate clearance supposedly by decreasing anaerobic threshold and causing premature entering to the anaerobic system

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy