Sympathetic circuits regulating hepatic glucose metabolism: where we stand.

The prevalence of metabolic disorders, including type 2 diabetes mellitus, continues to increase worldwide. Although newer and more advanced therapies are available, current treatments are still inadequate and the search for solutions remains. The regulation of energy homeostasis, including glucose metabolism, involves an exchange of information between the nervous systems and peripheral organs and tissues; therefore, developing treatments to alter central and/or peripheral neural pathways could be an alternative solution to modulate whole body metabolism. Liver glucose production and storage are major mechanisms controlling glycemia, and the autonomic nervous system plays an important role in the regulation of hepatic functions. Autonomic nervous system imbalance contributes to excessive hepatic glucose production and thus to the development and progression of type 2 diabetes mellitus. At cellular levels, change in neuronal activity is one of the underlying mechanisms of autonomic imbalance; therefore, modulation of the excitability of neurons involved in autonomic outflow governance has the potential to improve glycemic status. Tissue-specific subsets of preautonomic neurons differentially control autonomic outflow; therefore, detailed information about neural circuits and properties of liver-related neurons is necessary for the development of strategies to regulate liver functions via the autonomic nerves. This review provides an overview of our current understanding of the hypothalamus-ventral brainstem-liver pathway involved in the sympathetic regulation of the liver, outlines strategies to identify organ-related neurons, and summarizes neuronal plasticity during diabetic conditions with a particular focus on liver-related neurons in the paraventricular nucleus.

Type 2 Diabetes and HDL Dysfunction: A Key Contributor to Glycemic Control.

High-density lipoproteins (HDL) have been shown to exert multiple cardioprotective and antidiabetic functions, such as their ability to promote cellular cholesterol efflux and their antioxidant, anti-inflammatory, and antiapoptotic properties. Type 2 diabetes (T2D) is usually associated with low high-density lipoprotein cholesterol (HDL-C) levels as well as with significant alterations in the HDL composition, thereby impairing its main functions. HDL dysfunction also negatively impacts both pancreatic ß-cell function and skeletal muscle insulin sensitivity, perpetuating this adverse self-feeding cycle. The impairment of these pathways is partly dependent on cellular ATP-binding cassette transporter (ABC) A1-mediated efflux to lipid-poor apolipoprotein (apo) A-I in the extracellular space. In line with these findings, experimental interventions aimed at improving HDL functions, such as infusions of synthetic HDL or lipid-poor apoA-I, significantly improved glycemic control in T2D patients and experimental models of the disease. Cholesteryl ester transfer protein (CETP) inhibitors are specific drugs designed to increase HDLC and HDL functions. Posthoc analyses of large clinical trials with CETP inhibitors have demonstrated their potential anti-diabetic properties. Research on HDL functionality and HDL-based therapies could be a crucial step toward improved glycemic control in T2D subjects.

Stroke and Vascular Cognitive Impairment: The Role of Intestinal Microbiota Metabolite TMAO.

The gut microbiome interacts with the brain bidirectionally through the microbiome-gutbrain axis, which plays a key role in regulating various nervous system pathophysiological processes. Trimethylamine N-oxide (TMAO) is produced by choline metabolism through intestinal microorganisms, which can cross the blood-brain barrier to act on the central nervous system. Previous studies have shown that elevated plasma TMAO concentrations increase the risk of major adverse cardiovascular events, but there are few studies on TMAO in cerebrovascular disease and vascular cognitive impairment. This review summarized a decade of research on the impact of TMAO on stroke and related cognitive impairment, with particular attention to the effects on vascular cognitive disorders. We demonstrated that TMAO has a marked impact on the occurrence, development, and prognosis of stroke by regulating cholesterol metabolism, foam cell formation, platelet hyperresponsiveness and thrombosis, and promoting inflammation and oxidative stress. TMAO can also influence the cognitive impairment caused by Alzheimer's disease and Parkinson's disease via inducing abnormal aggregation of key proteins, affecting inflammation and thrombosis. However, although clinical studies have confirmed the association between the microbiome-gut-brain axis and vascular cognitive impairment (cerebral small vessel disease and post-stroke cognitive impairment), the molecular mechanism of TMAO has not been clarified, and TMAO precursors seem to play the opposite role in the process of poststroke cognitive impairment. In addition, several studies have also reported the possible neuroprotective effects of TMAO. Existing therapies for these diseases targeted to regulate intestinal flora and its metabolites have shown good efficacy. TMAO is probably a new target for early prediction and treatment of stroke and vascular cognitive impairment.

Sanpian decoction ameliorates cerebral ischemia-reperfusion injury by regulating SIRT1/ERK/HIF-1α pathway through in silico analysis and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia-reperfusion injury (CIRI) is a complex pathophysiological process involving multiple factors, and becomes the footstone of rehabilitation after ischemic stroke. Sanpian decoction (SPD) has exhibited protective effects against CIRI, migraine, and other cerebral vascular diseases. However, the underlying mechanisms have not been completely elucidated. AIM OF THE STUDY: This study sought to explore the potential mechanisms underlying the effect of SPD against CIRI. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography (UPLC) were carried out to determine the chemical constituents of SPD. A network pharmacology approach combined with experimental verification was conducted to elucidate SPD's multi-component, multi-target, and multi-pathway mechanisms in CIRI occurrence. The pharmacodynamics of the decoction was evaluated by establishing the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vivo and in vitro experiments were carried out, and the therapeutic effects of SPD were performed using 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Nissl staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and flow cytometry to evaluate cortex apoptosis. The quantification of mRNA and corresponding proteins were performed using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot respectively. RESULTS: Our research showed that pretreatment with SPD improved neurological function and inhibited CIRI. Network pharmacology revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway-mediated apoptosis may be associated with CIRI. In vivo and in vitro experiments, we confirmed that SPD increased cerebral blood flow, improved neural function, and reduced neural apoptosis via up-regulating the expression of sirtuin 1 (SIRT1) and down-regulating phospho-extracellular regulated protein kinases (p-ERK)/ERK and HIF-1α levels in CIRI rats. CONCLUSION: Taken together, the present study systematically revealed the potential targets and signaling pathways of SPD in the treatment of CIRI using in silico prediction and verified the therapeutic effects of SPD against CIRI via ameliorating apoptosis by regulating SIRT1/ERK/HIF-1α.

Traditional Chinese Medicine formula Wubi Shanyao Pills protects against reproductive aging by activating SIRT1/3 to reduce apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The study of male reproductive aging and its associated concerns holds significant importance within the realm of health issues affecting the elderly population. Wubi Shanyao Pills (WSP), a traditional Chinese patent medicine originating from the Tang Dynasty, has been recognized for its ability to enhance male sexual functions while also tonifying the kidney and spleen. Nevertheless, the precise effects and underlying mechanisms through which WSP ameliorates the decline in reproductive function among aging men remain uncertain. AIM OF THE STUDY: This study elucidated the distinctive impacts of WSP on ameliorating the decline in reproductive function caused by natural aging, as well as its underlying mechanisms. MATERIALS AND METHODS: Initially, male mice at the age of 15 months were administered WSP orally at doses of 0.375, 0.75, and 1.50 g/kg per day for a duration of 8 consecutive weeks. The impact of WSP on age-related manifestations in naturally aging mice was assessed based on their behavioral performance. The renal function of the mice was evaluated by measuring serum biochemical indicators, including Creatinine (CR), Uric acid (UA), and Blood urea nitrogen (BUN). Additionally, Superoxide dismutase (SOD) and Malonaldehyde (MDA) levels in renal tissue were determined using applied chemistry methods. Then assessed the levels of Nitric oxide (NO), Total nitric oxide synthase (T-NOS), Guanosine cyclase (GC), and Cyclic guanosine monophosphate (cGMP) in the penile tissue, as well as the expression of Endothelial nitric oxide synthase (eNOS) and Guanylate Cyclase Activator (GUCA) protein, in order to investigate the erectile function of the penis. Additionally, the quality of epididymal sperm was examined using an electron microscope. Furthermore, the serum sex hormone level and related protein expression were determined through the utilization of enzyme-linked immunosorbent assay and immunohistochemistry techniques. Pathological alterations and the ultrastructure of the testis were investigated using hematoxylin-eosin staining and transmission electron microscopy. Subsequently, the apoptosis of spermatogenic cells in the testes was assessed employing TUNEL, immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction. RESULTS: The administration of WSP has been found to enhance the behavioral performance and sexual behavior in aged mice. It's also could increase in serum levels of CR, UA, and BUN, as well as the elevation of SOD activity in kidney tissue, which subsequently leads to a reduction in MDA levels and an improvement in the structural damage caused by aging in the kidney tissue. Consequently, the renal function is enhanced. Additionally, WSP has been observed to elevate the levels of NO, T-NOS, GC, and cGMP in penile tissue, along with an increase in eNOS and GUCA protein expression, indicating an improvement in penile erectile function. The administration of WSP resulted in a decrease in the occurrence of programmed cell death in testicular germ cells, leading to an enhancement in sperm quality and the overall function of testicular spermatogenesis. This improvement can be attributed to the modulation of hormone levels and the regulation of SIRT1/3, p53, FOXO3, Bax, and Caspase-3 expression. CONCLUSION: Collectively, our findings indicate that the administration of WSP has the potential to impede the occurrence of programmed cell death in testicular cells by modulating the expression of SIRT1/3 and subsequent genes associated with apoptosis. Consequently, this regulatory mechanism facilitates the proliferation of testicular cells and sustains the spermatogenic function of the testes. Consequently, by modulating the levels of sexual hormones in naturally aging mice, WSP ultimately enhances the quality of sperm and reproductive function. Concurrently, it also ameliorates age-related behavioral changes, renal function, and erectile function.

Toddlers' affective responses to sociomoral scenes: Insights from physiological measures.

A growing literature suggests that preverbal infants are sensitive to sociomoral scenes and prefer prosocial agents over antisocial agents. It remains unclear, however, whether and how emotional processes are implicated in infants' responses to prosocial/antisocial actions. Although a recent study found that infants and toddlers showed more positive facial expressions after viewing helping (vs. hindering) events, these findings were based on naïve coder ratings of facial activity; furthermore, effect sizes were small. The current studies examined 18- and 24-month-old toddlers' real-time reactivity to helping and hindering interactions using three physiological measures of emotion-related processes. At 18 months, activity in facial musculature involved in smiling/frowning was explored via facial electromyography (EMG). At 24 months, stress (sweat) was explored via electrodermal activity (EDA). At both ages, arousal was explored via pupillometry. Behaviorally, infants showed no preferences for the helper over the hinderer across age groups. EMG analyses revealed that 18-month-olds showed higher corrugator activity (more frowning) during hindering (vs. helping) actions, followed by lower corrugator activity (less frowning) after hindering (vs. helping) actions finished. These findings suggest that antisocial actions elicited negativity, perhaps followed by brief disengagement. EDA analyses revealed no significant event-related differences. Pupillometry analyses revealed that both 18- and 24-month-olds' pupils were smaller after viewing hindering (vs. helping), replicating recent evidence with 5-month-olds and suggesting that toddlers also show less arousal following hindering than following helping. Together, these results provide new evidence with respect to whether and how arousal/affective processes are involved when infants process sociomoral scenarios.

Truthful yet misleading: Elementary second-order deception in school-age children and its sociocognitive correlates.

In highly competitive contexts, deceptive intentions might be transparent, so conveying only false information to the opponent can become a predictable strategy. In such situations, alternating between truths and lies (second-order lying behavior) represents a less foreseeable option. The current study investigated the development of 8- to 10-year-old children's elementary second-order deception in relation to their attribution of ignorance (first- and second-order ignorance) and executive functions (inhibitory control, shifting ability, and verbal working memory). An adapted version of the hide-and-seek paradigm was used to assess children's second-order lie-telling, in which children were asked to hide a coin in either of their hands. Unlike the standard paradigm, the opponent did not consistently look for the coin in the location indicated by the children, so children needed to switch between telling simple lies and truths (elementary second-order lies about the coin location) to successfully deceive the recipient. The results showed that older children were less likely to tell elementary second-order lies. However, across the sample, when children decided to lie, this ability was positively related to their second-order ignorance attribution and their verbal working memory. Moreover, we obtained preliminary evidence for the presence of a habituation effect in second-order lying, with children being more accurate and having less variability in their truthful-to-deceive responses (this being the more frequently elicited response) than when telling lies to deceive. Our findings could have implications for understanding the mechanisms underlying children's ability to alternate between truths and lies to deceive.

Steroid-responsive multifocal motor neuropathy with cranial manifestations - a case report.

The typical presentation of multifocal motor neuropathy (MMN) is progressive asymmetric limb weakness. Cranial neuropathy is rare. We report a 28-year-old woman with cranial and bulbar palsies but with typical electrophysiological features of MMN by multifocal motor conduction blocks and serological markers of anti-ganglioside GM1 antibodies. The previous consensus on the treatment of MMN is intravenous immunoglobulins, but our patient responded to oral steroids and had clinical and electrophysiological improvement under continuous low-dose prednisolone treatment. In summary, MMN is a treatable chronic inflammatory disease of peripheral nerves. Cranial neuropathies can be its initial presentations. Electromyography studies are crucial for MMN diagnosis and helpful in monitoring disease activity and treatment responses. Although the previous guideline did not suggest using steroids for MMN, with careful patient selection, low-dose oral steroids can be an effective treatment in patients with relatively minor symptoms. Keywords: Multifocal motor neuropathy, conduction block, bulbar palsy, cranial nerve, cranial neuropathy.

Determination of Solute Permeability of Microvascular Endothelial Cell Monolayers In Vitro.

The microvascular endothelium has a critical role in regulating the delivery of oxygen, nutrients, and water to the surrounding tissues. Under inflammatory conditions that accompany acute injury or disease, microvascular permeability becomes elevated. When microvascular hyperpermeability becomes uncontrolled or chronic, the excessive escape of plasma proteins into the surrounding tissue disrupts homeostasis and ultimately leads to organ dysfunction. Much remains to be learned about the mechanisms that control microvascular permeability. In addition to in vivo and isolated microvessel methods, the cultured endothelial cell monolayer protocol is an important tool that allows for understanding the specific, endothelial subcellular mechanisms that determine permeability of the endothelium to plasma proteins. In this chapter, two variations of the popular Transwell culture methodology to determine permeability to using fluorescently labeled tracers are presented. The strengths and weaknesses of this approach are also discussed.

Evaluation of Vascular Permeability in Inflamed Vessels of the Cremaster Muscle in Live Mice.

Inflammation in vascular structures due to external factors such as injury or infection inevitably leads to blood leakage. Therefore, measuring blood infiltrated into tissue may serve as an indication for the extent of an inflammatory reaction or injury. There are various methods of confirming vascular permeability in vivo and in vitro; for example, using a blood vessel permeable dye, the dye efflux can be quantitatively measured with a spectrophotometer. Although the aforementioned commonly used methods can measure leaked dye without difficulty, substantial limitations exist regarding the time points of blood leakage that can be measured. Here, we describe the details of a novel protocol to identify and analyze the real-time progression of blood leakage in vivo. This method, by combining existing methods with real-time imaging, is expected to immensely improve the visualization and evaluation of vascular permeability.

Studying Angiogenesis Using Matrigel In Vitro and In Vivo.

Angiogenesis plays a critical role in physiology and pathophysiology of the human body; hence, it is important to explore the methods to study angiogenesis under in vitro and in vivo settings. Here, we describe three different methods to assess angiogenesis using Matrigel: an in vitro two- or three-dimensional (2D/3D) tube formation or angiogenesis assay using endothelial cells with growth factor supplemented Matrigel, an ex vivo sprouting angiogenesis assay embedding aortic rings in the Matrigel, and finally, Matrigel plug assays wherein Matrigels are implanted into the flanks of mice to assess the recruitment of endothelial cells to form new blood vessels in vivo.

Association Between Physical Activity Levels in Different Domains and Cardiac Autonomic Modulation in Breast Cancer Survivors: A Cross-sectional Study.

BACKGROUND: Breast cancer survivors frequently present cardiac autonomic dysfunction. Physical activity (PA) has been associated with better cardiac autonomic modulation (CAM) in breast cancer survivors. OBJECTIVE: This study aimed to analyze the association between CAM and PA levels performed in different domains (work and occupation, sport and exercise, and leisure time and commuting) in breast cancer survivors. METHODS: This is a cross-sectional study with 99 breast cancer survivors (age, 55.3 ± 10.4 years). Cardiac autonomic modulation was assessed by heart rate variability, and PA levels at work and occupation, sport and exercise, and leisure time and commuting were assessed using the Baecke PA questionnaire. The sum of these 3 domains provided the total PA. The Mann-Whitney test was used to compare CAM between active and inactive women in different domains of PA. RESULTS: Cardiac autonomic modulation was similar between active and inactive women in the different domains ( P > .05). However, when considering the total PA, active breast cancer survivors presented higher SDNN (average standard deviation of all normal RR intervals) (20.0 ± 13.4 vs 28.8 ± 14.0; P = .008) and SD2 (standard deviation of the long-term intervals between consecutive heartbeats) indices (29.2 ± 17.3 vs 38.7 ± 19.9; P = .005) compared with their inactive counterparts. CONCLUSION: Breast cancer survivors with higher total PA presented better CAM compared with their less active peers. IMPLICATIONS FOR PRACTICE: The results of this study are promising and show the importance of increasing PA levels in different domains for the maintenance of cardiovascular health among breast cancer survivors.

Pharmacology in Treatment of Patients with Disorders of Consciousness.

Pharmacologic treatment of disorders of consciousness remains a critical but challenging task for clinicians. Amantadine has been shown to promote the rate of neurologic recovery for patients with traumatic disorders of consciousness when administered between 4 and 16 weeks, as demonstrated by a well-designed randomized control trial. While there are no large, randomized controlled trials to support the use of other dopaminergic medicines (bromocriptine, levodopa, apomorphine), there is a large body of literature implicating their role in improving alertness and responsiveness in disorders of consciousness. Zolpidem can increase the level of consciousness in a small subset of patients. Zolpidem and intrathecal baclofen likely increase the level of consciousness via the mesocircuit pathway. Psychostimulant medications can be initiated in patients, even without strong evidence to support their use, as long as basic principles of brain injury medicine are followed, and there are systems in place to evaluate therapeutic response.

Evaluation and Management of Disorders of Consciousness in the Acute Care Setting.

Acute disorders of consciousness (DOC) are impairments in arousal and awareness that occur within 28 days of an initial injury and can result from a variety of insults. These states range from coma, unresponsive wakefulness, covert consciousness, minimal consciousness, to confusional state. It is important to perform thorough, serial examinations with particular emphasis on the level of consciousness, brainstem reflexes, and motor responses. Evaluation of acute DOC includes laboratory tests, imaging, and electrophysiology testing. Prognostication in the acute phase of DOC must be done cautiously, using open, frequent communication with families, and by acknowledging significant multidimensional uncertainty.

Brain bases of morphological awareness and longitudinal word reading outcomes.

Children's spoken language skills are essential to the development of the "reading brain," or the neurocognitive systems that underlie successful literacy. Morphological awareness, or sensitivity to the smallest units of meaning, is a language skill that facilitates fluent recognition of meaning in print. Yet despite the growing evidence that morphology is integral to literacy success, associations among morphological awareness, literacy acquisition, and brain development remain largely unexplored. To address this gap, we conducted a longitudinal investigation with 75 elementary school children (5-11 years of age) who completed an auditory morphological awareness neuroimaging task at Time 1 as well as literacy assessments at both Time 1 and Time 2 (1.5 years later). Findings reveal longitudinal brain-behavior associations between morphological processing at Time 1 and reading outcomes at Time 2. First, activation in superior temporal brain regions involved in word segmentation was associated with both future reading skill and steeper reading gains over time. Second, a wider array of brain regions across the language network were associated with polymorphemic word reading as compared with broader word reading skill (reading both simple and complex words). Together, these findings reinforce the importance of word segmentation skills in learning to read and highlight the importance of considering complex word reading skills in building comprehensive neurocognitive models of literacy. This study fills a gap in our knowledge of how processing meaningful units in speech may help to explain differences in children's reading development over time and informs ongoing theoretical questions about the role of morphology in learning to read.

Evaluation of an Unloading Concept for Knee Osteoarthritis: A Pilot Study in a Small Patient Group.

Joint compressive forces have been identified as a risk factor for osteoarthritis disease progression. Therefore, unloader braces are a common treatment with the aim of relieving pain, but their effects are not clearly documented in the literature. A knee brace concept was tested with the aim of reducing joint loads and pain in knee osteoarthritis patients by applying an extension moment exclusively during the stance phase. The ideal effects were evaluated during gait based on musculoskeletal modeling of six patients, and experimental tests with a prototype brace were conducted on one patient. The effects were evaluated using electromyography measurements and musculoskeletal models to evaluate the muscle activation and knee compressive forces, respectively. The ideal brace simulations revealed a varying reduction of the first peak knee force between 3.5% and 33.8% across six patients whereas the second peak was unaffected. The prototype reduced the peak vasti muscle activation with 7.9% and musculoskeletal models showed a reduction of the first peak knee compressive force of up to 26.3%. However, the prototype brace increased the knee joint force impulse of up to 17.1% and no immediate pain reduction was observed. The reduction of the first peak knee compressive force, using a prototype on a single patient, indicates a promising effect from an applied knee extension moment for reducing knee joint loads during normal gait. However, further clinical experiments with this brace method are required to evaluate the long-term effects on both pain and disease progression in knee osteoarthritis patients.

Baroreflex Activation Therapy in Patients with Heart Failure with a Reduced Ejection Fraction.

A randomized, controlled trial of baroreflex activation therapy (BAT) in patients with heart failure and reduced ejection fraction demonstrated that BAT was safe and significantly improved patient-centered symptomatic outcomes, increasing exercise capacity, improving quality of life, decreasing n-terminal pro B-type natriuretic peptide (NT-proBNP), and improving functional class. BAT was approved by the FDA for improvement of symptoms of heart failure for patients who remain symptomatic despite treatment with guideline-directed management, are New York Heart Association Class III or Class II (with a recent history of Class III), have a left ventricular ejection fraction ≤ 35%, an NT-proBNP < 1600 pg/mL and excluding patients indicated for cardiac resynchronization therapy.

Preload Reduction Therapies in Heart Failure.

Preload reserve represents an important concept in the normal physiologic responses of the body to meet the changing metabolic demands. The recruitment of preload in healthy patients leads to an increase in effective circulating blood volume with a concomitant increase in cardiac output. However, in the setting of heart failure (HF), preload augmentation may precipitate HF decompensation. In this review, we focus on the role of splanchnic nerve modulation and pharmacological therapeutic interventions to prevent HF decompensation through preload reduction. Furthermore, we explore the emerging device-based approaches for cardiac preload reduction while reviewing the ongoing clinical trials.

Improvement of mnemonic discrimination with acute light exercise is mediated by pupil-linked arousal in healthy older adults.

Physical exercise has positive impacts on hippocampal memory decline with aging. One of the postulated neurobiological mechanisms of the decline is reduced catecholaminergic projections from the locus coeruleus to the hippocampus. Recent human studies revealed that very light exercise rapidly enhances memory and pupil diameter, which suggests that light exercise may improve memory via neural circuits involved in the ascending arousal system, including the locus coeruleus, even in older adults. Thus, we aimed to clarify the effects of a single bout of light-intensity exercise (60% ventilatory threshold) on mnemonic discrimination performance, an index of hippocampal memory function, in healthy older adults using a randomized crossover design. Pupil diameter was measured during exercise as a physiological marker of the ascending arousal system. Discrimination of highly similar stimuli to the targets improved after exercise when compared to the resting control performance. Importantly, causal mediation analysis showed that pupil dilation during exercise mediated the memory improvement. These results suggest that brief light exercise rapidly enhances memory, possibly by upregulating the ascending arousal system.

Forecasting freshwater cyanobacterial harmful algal blooms for Sentinel-3 satellite resolved U.S. lakes and reservoirs.

This forecasting approach may be useful for water managers and associated public health managers to predict near-term future high-risk cyanobacterial harmful algal blooms (cyanoHAB) occurrence. Freshwater cyanoHABs may grow to excessive concentrations and cause human, animal, and environmental health concerns in lakes and reservoirs. Knowledge of the timing and location of cyanoHAB events is important for water quality management of recreational and drinking water systems. No quantitative tool exists to forecast cyanoHABs across broad geographic scales and at regular intervals. Publicly available satellite monitoring has proven effective in detecting cyanobacteria biomass near-real time within the United States. Weekly cyanobacteria abundance was quantified from the Ocean and Land Colour Instrument (OLCI) onboard the Sentinel-3 satellite as the response variable. An Integrated Nested Laplace Approximation (INLA) hierarchical Bayesian spatiotemporal model was applied to forecast World Health Organization (WHO) recreation Alert Level 1 exceedance >12 µg L-1 chlorophyll-a with cyanobacteria dominance for 2192 satellite resolved lakes in the United States across nine climate zones. The INLA model was compared against support vector classifier and random forest machine learning models; and Dense Neural Network, Long Short-Term Memory (LSTM), Recurrent Neural Network (RNN), and Gneural Network (GNU) neural network models. Predictors were limited to data sources relevant to cyanobacterial growth, readily available on a weekly basis, and at the national scale for operational forecasting. Relevant predictors included water surface temperature, precipitation, and lake geomorphology. Overall, the INLA model outperformed the machine learning and neural network models with prediction accuracy of 90% with 88% sensitivity, 91% specificity, and 49% precision as demonstrated by training the model with data from 2017 through 2020 and independently assessing predictions with data from the 2021 calendar year. The probability of true positive responses was greater than false positive responses and the probability of true negative responses was less than false negative responses. This indicated the model correctly assigned lower probabilities of events when they didn't exceed the WHO Alert Level 1 threshold and assigned higher probabilities when events did exceed the threshold. The INLA model was robust to missing data and unbalanced sampling between waterbodies.