Citations

Abstract Parkinson’s disease (PD) is marked by degeneration in the nigrostriatal dopaminergic pathway, affecting motor control via complex changes in the cortico-basal ganglia-thalamic motor network, including the primary motor cortex (M1). The modulation of M1 neuronal activity by dopaminergic inputs, particularly from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), plays a crucial role in PD pathophysiology. This study investigates how nigrostriatal dopaminergic degeneration influences M1 neuronal activity in rats using in vivo calcium imaging. Histological analysis confirmed dopaminergic lesion severity, with high lesion level rats showing significant motor deficits. Levodopa treatment improved fine motor abilities, particularly in high lesion level rats. Analysis of M1 calcium signals based on dopaminergic lesion severity revealed distinct M1 activity patterns. Animals with low dopaminergic lesion showed increased calcium events, while high lesion level rats exhibited decreased activity, partially restored by levodopa. These findings suggest that M1 activity is more sensitive to transient fluctuations in dopaminergic transmission, rather than to chronic high or low dopaminergic signaling. This study underscores the complex interplay between dopaminergic signaling and M1 neuronal activity in PD symptoms development. Further research integrating behavioral and calcium imaging data can elucidate mechanisms underlying motor deficits and therapeutic responses in PD.

AbstractThe adiposity influence on colorectal cancer prognosis remains poorly characterised. We performed a systematic review and meta‐analysis on post‐diagnosis adiposity measures (body mass index [BMI], waist circumference, waist‐to‐hip ratio, weight) or their changes and colorectal cancer outcomes. PubMed and Embase were searched through 28 February 2022. Random‐effects meta‐analyses were conducted when at least three studies had sufficient information. The quality of evidence was interpreted and graded by the Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel. We reviewed 124 observational studies (85 publications). Meta‐analyses were possible for BMI and all‐cause mortality, colorectal cancer‐specific mortality, and cancer recurrence/disease‐free survival. Non‐linear meta‐analysis indicated a reverse J‐shaped association between BMI and colorectal cancer outcomes (nadir at BMI 28 kg/m2). The highest risk, relative to the nadir, was observed at both ends of the BMI distribution (18 and 38 kg/m2), namely 60% and 23% higher risk for all‐cause mortality; 95% and 26% for colorectal cancer‐specific mortality; and 37% and 24% for cancer recurrence/disease‐free survival, respectively. The higher risk with low BMI was attenuated in secondary analyses of RCTs (compared to cohort studies), among studies with longer follow‐up, and in women suggesting potential methodological limitations and/or altered physiological state. Descriptively synthesised studies on other adiposity‐outcome associations of interest were limited in number and methodological quality. All the associations were graded as limited (likelihood of causality: no conclusion) due to potential methodological limitations (reverse causation, confounding, selection bias). Additional well‐designed observational studies and interventional trials are needed to provide further clarification.

AbstractLow physical activity and high sedentary behaviour have been clearly linked with colorectal cancer development, yet data on their potential role in colorectal cancer survival is limited. Better characterisation of these relationships is needed for the development of post‐diagnosis physical activity and sedentary behaviour guidance for colorectal cancer survivors. We searched PubMed and Embase through 28 February 2022 for studies assessing post‐diagnosis physical activity, and/or sedentary behaviour in relation to all‐cause and cause‐specific mortality and recurrence after colorectal cancer diagnosis. Total and recreational physical activity were assessed overall and by frequency, duration, intensity, and volume using categorical, linear, and non‐linear dose–response random‐effects meta‐analyses. The Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel interpreted and graded the likelihood of causality. We identified 16 observational studies on 82,220 non‐overlapping patients from six countries. Physical activity was consistently inversely associated with colorectal cancer morbidity and mortality outcomes, with 13%–60% estimated reductions in risk. Sedentary behaviour was positively associated with all‐cause mortality. The evidence had methodological limitations including potential confounding, selection bias and reverse causation, coupled with a limited number of studies for most associations. The CUP Global Expert panel concluded limited‐suggestive evidence for recreational physical activity with all‐cause mortality and cancer recurrence. Total physical activity and its specific domains and dimensions, and sedentary behaviour were all graded as limited‐no conclusion for all outcomes. Future research should focus on randomised trials, while observational studies should obtain objective and repeated physical activity measures and better adjustment for confounders.

AbstractBased on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta‐analyses to investigate the association of post‐diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non‐linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J‐shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited‐no conclusion). The evidence on recreational physical activity and lower risk of all‐cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62–0.77) and recurrence/disease‐free survival (RR: 0.80, 95% CI: 0.70–0.92) was graded as limited‐suggestive. There was limited‐suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant‐based foods), intake of whole grains and coffee with lower risk of all‐cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all‐cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited‐no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well‐designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients.

Abstract The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post‐diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random‐effects dose–response meta‐analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all‐cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease‐free events). Meta‐analyses, including 3–10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega‐3 polyunsaturated fatty acids, supplemental calcium, circulating 25‐hydroxyvitamin D (25[OH]D) and all‐cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer‐specific mortality; and for circulating 25(OH)D and recurrence/disease‐free survival. The overall evidence was graded as ‘limited’. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant‐based foods), whole grains, total, caffeinated, or decaffeinated coffee and all‐cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all‐cause mortality provided ‘limited—suggestive’ evidence. All other exposure‐outcome associations provided ‘limited—no conclusion’ evidence. Additional, well‐conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.