Chapter Reviews Research Articles

Vitamin B12 and chronic kidney disease.

Chronic Kidney Disease (CKD) is an emerging public health issue with a fast-growing global prevalence. Impairment in vitamin B12 metabolism is considered a nontraditional risk factor of poor outcomes associated with CKD, and there is greater interest from the scientific community than ever before to explore the role and influence of vitamin B12 in CKD. Homocysteine metabolism forms an important component of the vitamin B12 metabolic pathway. Hyperhomocysteinemia is frequently observed in CKD and End-Stage Kidney Disease (ESKD), but its representation as a prognostic marker for CKD outcomes is still not fully clear. This chapter reviews the vitamin B12 and homocysteine metabolic pathways and their dysfunction in CKD states. Biochemical factors and the MTHFR genetic polymorphisms which disrupt vitamin B12 and homocysteine metabolism are explored. The mechanisms of homocysteine-mediated and vitamin B12-mediated tissue damage in CKD are discussed. This chapter reviews current perspective on definition and measurement of plasma vitamin B12 levels in the CKD population. Updated evidence investigating the prognostic role of vitamin B12 for CKD outcomes is presented. Findings from major clinical trials conducted relating to outcomes from multivitamin (including folic acid and vitamin B12) supplementation in nondialysis and dialysis-dependent CKD are highlighted. The prognostic value of vitamin B12 and effects of vitamin B12 supplementation in the context of kidney transplantation and acute kidney injury is also reviewed. Future research considerations are summarized based on evidence gaps in our knowledge base of this topic. Greater abundance of high-level evidence to guide an approach toward vitamin B12 measurement, monitoring and supplementation in CKD may contribute to improved clinical outcomes.

PET Use in Cancer Diagnosis, Treatment, and Prognosis.

Tumorigenesis is a multistep process marked by variations in numerous metabolic pathways that affect cellular architectures and functions. Cancer cells reprogram their energy metabolism to enable several basic molecular functions, including membrane biosynthesis, receptor regulations, bioenergetics, and redox stress. In recent years, cancer diagnosis and treatment strategies have targeted these specific metabolic changes and the tumor's interactions with its microenvironment. Positron emission tomography (PET) captures all molecular alterations leading to abnormal function and cancer progression. As a result, the development of PET radiotracers increasingly focuses on irregular biological pathways or cells that overexpress receptors that have the potential to function as biomarkers for early diagnosis and treatment measurements as well as research. This chapter reviews both established and evolving PET radiotracers used to image tumor biology. We have also included a few advantages and disadvantages of the routinely used PET radiotracers in cancer imaging.

Cognitive dysfunction and neuropsychiatric aspects of Parkinson's disease.

Movement abnormalities, by definition, and cognitive changes, to varying extents, affect every patient with Parkinson's disease (PD) and are attributed to the underlying neurodegenerative disease. Various psychiatric disorders occur in most patients at some point over the course of PD, including in the prodromal phase. Even though psychiatric disturbances tend to aggravate motor and cognitive deficits, they are under-recognized and under-treated, and the role of the underlying neurological disease is often minimized. To provide an integrated approach to understanding neuropsychiatric aspects of PD, this chapter reviews how cognitive changes in PD relate to the common psychiatric disturbances in PD along with the prevalence, phenomenology, pathophysiology, and treatment of each.

Functional neuroanatomy of cognition in Parkinson's disease.

While cognitive dysfunction in Parkinson's disease (PD) is increasingly recognized as a progressive symptom of the underlying neurodegenerative disease, our understanding of the functional and structural anatomic changes underlying these cognitive changes remains incomplete. Like the motor system, research point to a complex interplay between multiple parallel yet interconnected networks or circuits that are affected in PD and give rise to cognitive symptomatology. These circuits are most often studied in the context of disorders of executive function, and tightly linke to frontal lobe dysfunction. While the tasks employed vary across studies and it is often unclear whether differences in anatomy and function are causal or compensatory, the literature points to several key circuits that seem to be uniquely impaired in PD patients with cognitive dysfunction. This chapter reviews four of these circuits including the frontostriatal, frontoparietal, mesocortical, and noradrenergic circuits. By gaining a better understanding of the functional neuroanatomy of these circuits, we begin to develop a more comprehensive and unifed picture of how they to account for the pathophysiology of cognitive dysfunction in PD.

Weight Loss Strategies.

Lifestyle interventions for weight loss combine support for changing diet and physical activity with weight management education and are considered the first line treatment for obesity. A variety of diet-focused interventions including time-restricted eating are also increasingly being promoted for weight management. This chapter reviews different types of interventions for weight management, their underlying health behavior change models, and effectiveness to date in randomized trials. The results justify increasing efforts to improve program effectiveness generally, and to personalize interventions to support long-term adherence. The high prevalence of obesity worldwide, combined with the known increase in risk of non-communicable diseases with duration of excess weight, provides a compelling justification for routine delivery of effective weight management interventions in the community and in clinical care.

Biology of quinoline and quinazoline alkaloids.

Quinoline and quinazoline alkaloids, two important classes of N-based heterocyclic compounds, have attracted scientific and popular interest worldwide since the 19th century. More than 600 compounds have been isolated from nature to date. To build on our two prior reviews, we reexamined the promising molecules described in previous reports and provided updated literature on novel quinoline and quinazoline alkaloids isolated over the past 5 years. This chapter reviews and discusses 205 molecules with a broad range of bioactivities, including antiparasitic and insecticidal, antibacterial and antifungal, cardioprotective, antiviral, anti-inflammatory, and other effects. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.

Chapter 1 - Respiratory rhythm and pattern generation: Brainstem cellular and circuit mechanisms

Breathing movements in mammals are driven by rhythmic neural activity automatically generated within spatially and functionally organized brainstem neural circuits comprising the respiratory central pattern generator (CPG). This chapter reviews up-to-date experimental information and theoretical studies of the cellular and circuit mechanisms of respiratory rhythm and pattern generation operating within critical components of this CPG in the lower brainstem. Over the past several decades, there have been substantial advances in delineating the spatial architecture of essential medullary regions and their regional cellular and circuit properties required to understand rhythm and pattern generation mechanisms. A fundamental concept is that the circuits in these regions have rhythm-generating capabilities at multiple cellular and circuit organization levels. The regional cellular properties, circuit organization, and control mechanisms allow flexible expression of neural activity patterns for a repertoire of respiratory behaviors under various physiologic conditions that are dictated by requirements for homeostatic regulation and behavioral integration. Many mechanistic insights have been provided by computational modeling studies driven by experimental results and have advanced understanding in the field. These conceptual and theoretical developments are discussed.

Motoneuronal Regulation of Central Pattern Generator and Network Function.

This chapter reviews recent work showing that vertebrate motoneurons can trigger spontaneous rhythmic activity in the developing spinal cord and can modulate the function of several different central pattern generators later in development. In both the embryonic chick and the fetal mouse spinal cords, antidromic activation of motoneurons can trigger bouts of rhythmic activity. In the neonatal mouse, optogenetic manipulation of motoneuron firing can modulate the frequency of fictive locomotion activated by a drug cocktail. In adult animals, motoneurons have been shown to regulate swimming in the zebrafish, and vocalization in fish and frogs. We discuss the significance of these findings and the degree to which motoneurons may be considered a part of these central pattern generators.

Chapter 11 - Dyspnea

The clinical term dyspnea (a.k.a. breathlessness or shortness of breath) encompasses at least three qualitatively distinct sensations that warn of threats to breathing: air hunger, effort to breathe, and chest tightness. Air hunger is a primal homeostatic warning signal of insufficient alveolar ventilation that can produce fear and anxiety and severely impacts the lives of patients with cardiopulmonary, neuromuscular, psychological, and end-stage disease. The sense of effort to breathe informs of increased respiratory muscle activity and warns of potential impediments to breathing. Most frequently associated with bronchoconstriction, chest tightness may warn of airway inflammation and constriction through activation of airway sensory nerves. This chapter reviews human and functional brain imaging studies with comparison to pertinent neurorespiratory studies in animals to propose the interoceptive networks underlying each sensation. The neural origins of their distinct sensory and affective dimensions are discussed, and areas for future research are proposed. Despite dyspnea's clinical prevalence and impact, management of dyspnea languishes decades behind the treatment of pain. The neurophysiological bases of current therapeutic approaches are reviewed; however, a better understanding of the neural mechanisms of dyspnea may lead to development of novel therapies and improved patient care.

HDL Mimetic Peptides.

Since therapeutic strategies designed to raise HDL failed to exert the expected effective cardiovascular disease (CVD) outcomes in clinical trials, how to improve HDL function rather than its plasma level has become a new focus of scientists' attention. Numerous HDL mimetic peptides have been designed and investigated in various animal models in recent years. Although the underlying mechanisms are not fully understood, the peptides' antiatherogenic effects, such as acceleration of RCT and improvement of natural HDL function without necessarily raising its level, showed a promising therapeutic role in theprevention of atherosclerosis and other diseases. This chapter reviews recent studies on the roles and potentials of HDL mimetic peptides in atherosclerosis-related CVD.

Luminal Chemoreceptors and Intrinsic Nerves: Key Modulators of Digestive Motor Function.

This chapter reviews data on the pathways by which luminal, mainly duodenal, chemoreceptors modulate gastro-pyloro-duodenal motor function to control emptying of nutrients into the small intestine. The vagus mediates proximal gastric relaxation caused by nutrient stimulation of duodenal/jejunal mucosal chemoreceptors. Modulation of the spatial patterning and inhibition of antral contractions during duodenal chemoreceptor activation are somewhat conflicting: both vagal control and ascending intramural nerves appear to play a role. Intraduodenal nutrients stimulate the localized pyloric contractions that prevent transpyloric flow via ascending duodenal intramural nerve pathways. Though not yet formally investigated, patterns of activation of the duodenal brake motor mechanism suggest that duodenal loop mucosal chemoreceptors signal to a brake mechanism at the most aborad region of the duodenum via descending intramural duodenal nerves.Intrinsic intramural pathways are important in the control of the first stages of digestion.

Machine Learning Models for Predicting Liver Toxicity.

Liver toxicity is a major adverse drug reaction that accounts for drug failure in clinical trials and withdrawal from the market. Therefore, predicting potential liver toxicity at an early stage in drug discovery is crucial to reduce costs and the potential for drug failure. However, current in vivo animal toxicity testing is very expensive and time consuming. As an alternative approach, various machine learning models have been developed to predict potential liver toxicity in humans. This chapter reviews current advances in the development and application of machine learning models for prediction of potential liver toxicity in humans and discusses possible improvements to liver toxicity prediction.

Strains and Molecular Tools for Recombinant Protein Production in Pichia pastoris.

Within the last two decades, the methylotrophic yeast Pichia pastoris (Komagataella phaffii) has become an important alternative to E. coli or mammalian cell lines for the production of recombinant proteins. Easy handling, strong promoters, and high cell density cultivations as well as the capability of posttranslational modifications are some of the major benefits of this yeast. The high secretion capacity and low level of endogenously secreted proteins further promoted the rapid development of a versatile Pichia pastoris toolbox. This chapter reviews common and new "Pichia tools" and their specific features. Special focus is given to expression strains, such as different methanol utilization, protease-deficient or glycoengineered strains, combined with application highlights. Different promoters and signal sequences are also discussed.

Integration of Crop Growth Models and Genomic Prediction.

Crop growth models (CGMs) consist of multiple equations that represent physiological processes of plants and simulate crop growth dynamically given environmental inputs. Because parameters of CGMs are often genotype-specific, gene effects can be related to environmental inputs through CGMs. Thus, CGMs are attractive tools for predicting genotype by environment (G×E) interactions. This chapter reviews CGMs, genetic analyses using these models, and the status of studies that integrate genomic prediction with CGMs. Examples of CGM analyses are also provided.

Targeting Cancer by Using Nanoparticles to Modulate RHO GTPase Signaling.

Functionalized nanomaterials have recently been introduced as efficient vehicles for targeted delivery of drugs and other tailored molecules to cancer cells. They emerge as new opportunities for addressing particular challenging targets such as RHO guanosine triphosphatases (GTPases), a group of signaling molecules involved in the progression of a variety of tumor types. RHO GTPases comprise a subfamily of the Ras superfamily of small GTPases. They are best known for their role in cell migration through the remodeling of the actin cytoskeleton. However, they are also key regulators of a broad number of cellular functions, ranging from proliferation to cell adhesion and differentiation. Not surprisingly, their dysregulation has been implicated in the development and progression of many types of cancer. The RHO GTPase subfamily includes 20 members that can be further separated into typical and atypical RHO GTPases. The typical RHO family members include the classical RHOA, RAC1 and CDC42 proteins, which cycle between an active GTP-bound and inactive GDP-bound conformation, under the coordinated action of three types of regulators: GEFs, GAPs and GDIs. Atypical RHO family members have small changes in key residues that alter their regulatory mechanisms. Nevertheless, both typical and atypical RHO GTPases contribute to cancer progression but, in contrast to Ras proteins, very few mutations have been found in tumors. In most cancers, it is the expression level and/or activity of RHO GTPases that is dysregulated. RHO GTPase signaling has thus long been seen as an attractive target for cancer treatment but their ubiquity and the lack of isoform-specific drugs have posed significant obstacles to the development of viable therapeutic strategies. Based on the success of recent nanomedicine approaches, this chapter reviews representative studies of how functionalized nanoparticles can be designed to target tumor-specific molecules and directly or indirectly modulate the expression and/or activity of particular RHO GTPases in cancer cells.

Trajectories of Curriculum Change in Initial Primary Teacher Education in Zambia

This chapter reviews trends in primary teacher education for the last five decades in Zambia. Since independence, Zambia has undertaken the following curriculum reforms in primary teacher education; the Zambia Primary Course(ZPC), The Zambia Basic Education Course(ZBEC), The Field Based Teacher Training Approach(FIBATTA) which was discontinued hardly three months of trial, The Zambia Teacher Education Reform Programme(ZATERP) piloted in three colleges of education, The Zambia Teacher Education Course(ZATEC-one year college based and one year school-based);the Zambia Teacher Education Course(ZATEC-two year residential course) and the current three year Diploma Primary Teacher Education Programme. The Ministry of Education upgraded all primary colleges of education to Diploma status and affiliated them to the University of Zambia. For a couple of years, the Ministry of Education back peddled and attached all Colleges of Education to the Examinations Council of Zambia (ECZ), a decision that was roundly condemned as a departure from the SADC protocol on education. Meanwhile, Colleges of Education which were under ECZ have now reverted to the University of Zambia with respect to quality assurance and programme supervision.

AKT Isoforms in the Immune Response in Cancer.

AKT is a protein kinasethat exists in three isoforms: AKT1, AKT2, and AKT3. Though similar in structure, these isoforms display different effects. AKT is activated downstream of PI3K, and together, this signaling pathway helps regulate cellular processes including cell growth, proliferation, metabolism, survival, and apoptosis. Disruption in these pathways has been associated with disorders including cardiovascular diseases, developmental disorders, inflammatory responses, autoimmune diseases, neurologic disorders, type 2 diabetes, and several cancers. In cancer, deregulation in the PI3K/AKT pathway can be manifested as tumorigenesis, pathological angiogenesis, and metastasis. Increased activity has been correlated with tumor progression and resistance to cancer treatments. Recent studies have suggested that inhibition of the PI3K/AKT pathway plays a significant role in the development, expansion, and proliferation of cells of the immune system. Additionally, AKT has been found to play an important role in differentiating regulatory T cells, activating B cells, and augmenting tumor immunosurveillance. This emphasizes AKT as a potential target for inhibition in cancer therapy. This chapter reviews AKT structure and regulation, its different isoforms, its role in immune cells, and its modulation in oncotherapy.

Recent Neuroscience Advances in Human Parenting.

The transition to parenthood entails brain adaptations to the demands of caring for a newborn. This chapter reviews recent neuroscience findings on human parenting, focusing on neuroimaging studies. First, we describe the brain circuits underlying human maternal behavior, which comprise ancient subcortical circuits and more sophisticated cortical regions. Then, we present the short-term and long-term functional and structural brain adaptations that characterize the transition to motherhood, discuss the long-term effects of parenthood on the brain, and propose several underlying neural mechanisms. We also review neuroimaging findings in biological fathers and alloparents (such as other relatives or adoptive parents), who engage in parenting without directly experiencing pregnancy or childbirth. Finally, we describe perinatal mental illnesses and discuss the neural responses associated with such disorders. To date, studies indicate that parenthood is a period of enhanced brain plasticity within brain areas critical for cognitive and social processing and that both parenting experience and gestational-related factors can prime such plasticity.

Chapter 10 - Visual objects and their colors

The ventral temporal cortex hosts key regions for the high-level visual processing of object shape and color. These areas represent nodes of large-scale neural circuits dedicated to object recognition. In the language-dominant hemisphere, some of these regions communicate with the language systems; by assigning verbal labels to percepts, these circuits speedup stimulus categorization, and permit fast and accurate interindividual communication. By impairing the functioning of these circuits, neurological damage may provoke disabling disorders of the processing of visual objects and of their colors. Brain damage of vascular, degenerative, toxic, or traumatic origin can induce deficits at different levels of visual processing, from the building of shape- or wavelength-invariant percepts, to their connections with semantic knowledge and with the appropriate lexical entry. After an overview of the neuroimaging of domain-preferring regions for object shape and color in the ventral temporal cortex, this chapter reviews evidence from historical and recent cases of acquired visual agnosia and color processing deficits. A recurrent motif emerging from patients' patterns of performance and lesion locations is the existence of caudo-rostral gradients in the ventral occipito-temporal cortex, spanning from more perceptual to more cognitive stages of processing.

Ultrasonic Evaluation of the Bone-Implant Interface.

While implant surgical interventions are now routinely performed, failures still occur and may have dramatic consequences. The clinical outcome depends on the evolution of the biomechanical properties of the bone-implant interface (BII). This chapter reviews studies investigating the use of quantitative ultrasound (QUS) techniques for the characterization of the BII.First, studies on controlled configurations evidenced the influence of healing processes and of the loading conditions on the ultrasonic response of the BII. The gap of acoustical properties at the BII increases (i) during healing and (ii) when stress at the BII increases, therefore inducing a decrease of the reflection coefficient at the BII.Second, an acoustical model of the BII is proposed to better understand the parameters influencing the interaction between ultrasound and the BII. The reflection coefficient is shown to decrease when (i) the BII is better osseointegrated, (ii) the implant roughness decreases, (iii) the frequency of QUS decreases and (iv) the bone mass density increases.Finally, a 10MHz device aiming at assessing dental implant stability was validated in vitro, in silico and in vivo. A comparison between QUS and resonance frequency analysis (RFA) techniques showed a better sensitivity of QUS to changes of the parameters related to the implant stability.