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Md Anwarul Azim Majumder,1,2 Keerti Singh,2 WMS Johnson,3 Archana Rajasundaram,3 Subir Gupta,2 Uma Gaur,2 Santosh Kumar,4 Madhuri Chatterjee,5 Ahbab Mohammad Fazle Rabbi,6 Vijay Prasad Sangishetti,7 Sayeeda Rahman,8 Michael H Campbell,2 Heather Harewood,2 Ambadasu Bharatha,2 Kandamaran Krishnamurthy,2 Russell Kabir,9 Ali Davod Parsa,9 Shegufta Mohammmad,10 Mainul Haque,11 Mohammed S Razzaque12 1Public Health Foundation of Bangladesh, Dhaka, Bangladesh; 2Faculty of Medical Sciences, The University of the West Indies, Bridgetown, Barbados; 3Department of Anatomy, Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India; 4Karnavati School of Dentistry, Karnavati University, Ahmedabad, Gujarat, India; 5Department of Pharmacology, Shri Ramkrishna Institute of Medical Science, Durgapur, West Bengal, India; 6Department of Population Sciences, University of Dhaka, Dhaka, Bangladesh; 7Department of Pharmacology, Govt. Medical College, Shivpuri, Madhya Pradesh, India; 8School of Medicine, American University of Integrative Sciences (AUIS), Bridgetown, Barbados; 9Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Chelmsford, Essex, UK; 10BRAC Learning Division, BRAC University, Dhaka, Bangladesh; 11Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kuala Lumpur, 57000, Malaysia; 12Lake Erie College of Osteopathic Medicine, Erie, PA, USACorrespondence: WMS Johnson, Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India, Email johnsonmoses@gmail.com; johnsonmoses@yahoo.com Mainul Haque, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia, Email runurono@gmail.com; mainul@upnm.edu.myBackground: Efficacy and safety are fundamental for the development of successful COVID-19 vaccines. Vaccine-associated side effects influence vaccine hesitancy. This study investigated the prevalence, severity, and onset of side effects following the first dose of COVID-19 vaccines among physicians and dentists working in various healthcare settings across India.Methods: A cross-sectional survey collected self-report data from April to June 2021 on side effects following the first dose of the vaccine. An online validated questionnaire using the Google Docs® platform was circulated via email and social media platforms.Results: More than 40% of participants experienced at least one side effect after the first dose of vaccination; the most common were mild and resolved within three days after vaccination. More than 91% of respondents received the Covishield (AstraZeneca) vaccine; the most prevalent adverse effects were soreness of the injected arm (78.9%), tiredness (71.1%), and fever (54.9%). Logistic regression showed that women were almost 60% less likely to report side effects.Conclusion: Findings supported the safety of the first dose of the COVID-19 vaccine based on relatively few self-limiting side effects, mainly soreness of the injected arm and tiredness. Further research is needed to determine the long-term safety of COVID-19 vaccines, especially after booster doses.Keywords: prevalence, adverse effects, COVID-19 vaccine, physicians, dentists, India

Superstition is a belief that is not based on scientific knowledge. Traditional healers usually use superstition in their practices to manage human health problems and diseases; such practices create a conflict with the medical profession and its evidence-based practices. Medical professionals confirm that this kind of practice is unsafe as it is performed by untrained people (e.g., traditional healers) utilizing unsterilized instruments within unhygienic environments. Most of the cases eventually develop a variety of complications, which are sometimes fatal. Female genital mutilation, uvulectomy, oral mutilation (tooth bud extraction to cure “Ibyinyo”), and eyebrow incisions are examples of the many different types of superstitious practices which occur commonly in other parts of the world. We describe how these traditional practices of superstition have been and continue to be performed in various parts of the world, their complications on oral and general health, and how such practices hinder modern medical practices and highlight huge inequalities and disparities in healthcare-seeking behavior among different social groups. This paper aims to increase health literacy and awareness of these superstition-driven traditional and potentially harmful practices by promoting the importance of evidence-based medical practices.

5-Aminolevulinic acid (5-ALA) is a naturally synthesized amino acid present in most plants as well as animals, and it is routinely consumed by humans. This brief report sought to describe the potential of 5-ALA and sodium-ferrous citrate (5-ALA/SFC) to ameliorate the course of coronavirus disease 2019 (COVID-19).: Studies have shown that 5-ALA is converted to protoporphyrin IX (PPIX), then to heme. Recent studies have demonstrated that PPIX has antiviral effects against several viruses, including Zika virus, dengue virus, and influenza A virus. The anti-inflammatory effects of 5-ALA have also been reported in humans. Preliminary in vitro and clinical studies have shown that the combination of 5-ALA/SFC could reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated insults. The SARS-CoV-2 genome contains guanine-quadruplex sequences, and the administration of 5-ALA/SFC can lead to the generation of porphyrins that have the ability to bind to guanine-quadruplexes and reduce the replication of SARS-CoV-2. Furthermore, 5-ALA is a metabolic precursor of heme, which is a potent inducer of the enzyme heme oxygenase-1, the levels of which are decreased in patients with severe COVID-19. Oral administration of 5-ALA/SFC induced heme oxygenase-1 in the peripheral blood of uninfected healthy individuals.: Based on the available information, it appears likely that 5-ALA/SFC has therapeutic value in clinically controlling SARS-CoV-2-mediated insults in COVID-19 patients. Multicenter randomized controlled trials are needed for determining the long-term clinical utility of 5-ALA/SFC.

Muscle cachexia has a major detrimental impact on cancer patients, being responsible for 30% of all cancer deaths. It is characterized by a debilitating loss in muscle mass and function, which ultimately deteriorates patients’ quality of life and dampens therapeutic treatment efficacy. Muscle cachexia stems from widespread alterations in whole-body metabolism as well as immunity and neuroendocrine functions, and these global defects often culminate in aberrant signaling within skeletal muscle, causing muscle protein breakdown and attendant muscle atrophy. This review summarizes recent landmark discoveries that significantly enhance our understanding of the molecular etiology of cancer-driven muscle cachexia, and further discuss emerging therapeutic approaches seeking to simultaneously target those newly-discovered mechanisms to efficiently curb this lethal syndrome.

Fibroblast growth factor‐23 (FGF23) controls the homeostasis of both phosphate and vitamin D. Bone-derived FGF23 can suppress the transcription of 1α‐hydroxylase (1α(OH)ase) to reduce renal activation of vitamin D (1,25(OH)2D3). FGF23 can also activate the transcription of 24‐hydroxylase to enhance the renal degradation process of vitamin D. There is a counter-regulation for FGF23 and vitamin D; 1,25(OH)2D3 induces the skeletal synthesis and the release of FGF23, while FGF23 can suppress the production of 1,25(OH)2D3 by inhibiting 1α(OH)ase synthesis. Genetically ablating FGF23 activities in mice resulted in higher levels of renal 1α(OH)ase, which is also reflected in an increased level of serum 1,25(OH)2D3, while genetically ablating 1α(OH)ase activities in mice reduced the serum levels of FGF23. Similar feedback control of FGF23 and vitamin D is also detected in various human diseases. Further studies are required to understand the subcellular molecular regulation of FGF23 and vitamin D in health and disease.

Zinc finger protein 1 (ZPR1) is required for cellular replication and viability. Recently, ZPR1 variant rs964184 has been repeatedly linked to high plasma triglyceride levels, metabolic syndrome, type 2 diabetes mellitus (T2DM), and nonalcoholic fatty liver disease (NAFLD), suggesting its involvement in lipid metabolism. This article attempts to explain how ZPR1 contributes to the mechanism of high-fat diet-associated cognitive decline through three premises: i) high-fat diet results in cognitive decline, ii) ZPR1 deficiency also results in cognitive decline, and iii) high-fat diet results in ZPR1 deficiency. Therefore, ZPR1 has the potential to be the connection between high-fat diet and cognitive decline. The two modalities of cognitive decline caused by low concentrations of ZPR1 are reduced brain-derived growth factor (BDNF) synthesis and neuron death, both occurring in the hippocampus. Downregulation of ZPR1 may lead to decreased synthesis of BDNF due to reduced concentrations of peroxisome proliferator-activated receptor-gamma (PPAR-γ), tropomyosin receptor kinase B (Trk B), and cAMP response element-binding protein (CREB), resulting in reduced ability to form and retain long-term memory as well as reduced neuroplasticity. Likewise, low concentrations of ZPR1 facilitate neuron death by producing lower amount of spinal motor neuron (SMN) protein, causing genomic instability, activating mixed-lineage protein kinase 3 (MLK3), mitogen-activated protein kinase 7 (MKK7), and c-Jun N-terminal kinase 3 (JNK3) signal cascade, and ultimately resulting in the activation of Caspase 3., Highlights • ZPR1 plays an important role in cell division and viability. • ZPR1 variant rs964184 has been linked to dysregulation of lipid metabolism. • High-fat diet can reduce ZPR1 to induce hippocampal neuronal death. • High-fat diet correlates with cognitive decline. • ZPR1 may mediate high-fat diet-induced cognitive decline.

The Recommended Dietary Allowance (RDA) for phosphate in the U.S. is around 700 mg/day for adults. The majority of healthy adults consume almost double the amount of phosphate than the RDA. Lack of awareness, and easy access to phosphate-rich, inexpensive processed food may lead to dietary phosphate overload with adverse health effects, including cardiovascular diseases, kidney diseases and tumor formation. Nutritional education and better guidelines for reporting phosphate content on ingredient labels are necessary, so that consumers are able to make more informed choices about their diets and minimize phosphate consumption. Without regulatory measures, dietary phosphate toxicity is rapidly becoming a global health concern, and likely to put enormous physical and financial burden to the society.

Systemic phosphate homeostasis is tightly controlled by the delicate cross-organ talk among intestine, kidney, bone, and parathyroid glands. The endocrine regulation of phosphate homeostasis is primarily mediated by fibroblast growth factor 23 (FGF23), vitamin D, and parathyroid hormone (PTH). Bone-derived FGF23 acts on the proximal tubular epithelial cells of the kidney to partly maintain the homeostatic balance of the phosphate. FGF23, through binding with its cell surface receptors in the presence of klotho, can activate downstream signaling kinases to reduce the functionality of the sodium-phosphate (NaPi) co-transporters of the kidney to influence the systemic phosphate homeostasis. Given the complexity of molecular regulation of phosphate homeostasis, providing information on all aspects of its homeostatic control in a single volume of a book is an overwhelming task. As the Editor, I have organized the chapters that I believe will provide necessary information on the physiologic regulation and pathologic dysregulation of phosphate in health and diseases. Readers will be able to use this volume as a quick reference for updated information on phosphate metabolism without prior acquaintance with the field.

The endocrine regulator proteins, fibroblast growth factor 23 (FGF23) and Klotho have been well studied as mediators of phosphate metabolism. FGF23 has been implicated in the renal excretion of phosphate by limiting the docking of sodium-dependent phosphate transporters, Npt2a and Npt2c, into the luminal side of renal proximal tubular epithelial cells. By limiting Npt2a/c activity in the renal tubular epithelial cells, phosphate is reabsorbed at lower rates and is excreted at higher rates. The action of Klotho is relatively less understood but has been implicated as an FGF23 cofactor in receptor binding. Klotho is mostly synthesized in the distal tubules of the nephron relative to FGF23's activity in proximal renal tubules. The neurological sequelae due to alterations in the FGF23-Klotho axis may be explained by the direct effects of these phosphate-regulating proteins on neuronal tissues or by the roles of these proteins in phosphate metabolism. Hyperphosphatemia has been associated with vascular wall stiffness that may alter blood flow and weakenvessels in the brain. In contrast, hypophosphatemia may alter ATP usage and metabolism in the central nervous system (CNS), leading to neurological compromise. Altered levels of FGF23 and Klotho have both been associated with neurocognitive decline, clinical dementia, memory loss, and poor executive function in humans. Furthermore, FGF23 and Klotho dysregulation has been linked to structural and functional changes of the cardiovascular system with an increased risk of stroke. Subsequent research should focus on characterizing the neuropathology associated with alterations in the FGF23-Klotho system and dysregulated phosphate metabolism.

The underlying role of inadequate or excess intake of phosphate is evident in disease states, including metabolic, skeletal, cardiac, kidney and various cancers. Elevated phosphate levels can induce epithelial to mesenchymal transition (EMT) and cell death. EMT and associated lethal, metastatic or fibrinogenic responses are known to be underlying disease processes in fibrotic diseases and various solid tumors. Studies have shown EMT is regulated by induction of different signaling pathways, including TGF-β, RTK, SRC, Wnt and Notch signal transduction. However, cross-talk amongst these signaling pathways is less understood. We have shown that elevated phosphate levels enhanced EMT partially through activating ERK1/2 pathway, resulting in massive cell death. We thus proposed excess phosphate-mediated lethal EMT as one of the underlying mechanisms of phosphate-induced cytotoxicity, which could explain high phosphate-associated renal fibrosis and cancer metastasis in preclinical and clinical studies. This chapter provides the overview of EMT with the highlights of its regulation by various signaling pathways induced by phosphate toxicity. We further put lately reported lethal EMT in the context of phosphate toxicity with the intent to explain it to excessive phosphate-associated pathologies.

Vitamin D plays an essential role in calcium and inorganic phosphate (Pi) homeostasis, maintaining their optimal levels to assure adequate bone mineralization. Vitamin D, as calcitriol (1,25(OH)

Phosphate is an essential macromineral often introduced to the body through dietary intake. The mechanisms for maintaining phosphate levels are tightly controlled via hormonal interactions and excretion via the kidneys. However, western diets consist of high levels of inorganic phosphate, which can overwhelm the regulatory mechanisms in place for maintaining homeostasis. Recent studies have found that phosphate burden can lead to activation of inflammatory signaling in various parts of the body. In addition, individuals with impaired kidney function may also experience exacerbated symptoms of phosphate overload due to decreased filtration and elimination. Many disease states can arise as a result of phosphate burden and subsequent inflammatory signaling, including cardiovascular diseases, tumorigenesis, depression, and neuronal disorders. While the pathophysiological causes of these diseases have been elucidated, there remains a need to address the clinical impacts of excessive dietary phosphate intake and to clarify potential drug candidates that may help alleviate these conditions. This brief chapter looks to explain the overall connection between phosphate burden and inflammation in various diseases.

Fibroblast growth factor 23 (FGF23) is a hormone produced by osteocytes in bone that acts on the kidneys to regulate phosphate and vitamin D metabolism.FGF23 levels were shown to be increased in the early stage of chronic kidney disease (CKD), with a slight decline in estimated glomerular filtration rate (eGFR) even when the range was restricted to above 60 mL/min/1.73 m

Phosphorus is an essential nutrient that plays a crucial role in various biological processes, including cell membrane integrity, synthesis of nucleic acids, energy metabolism, intracellular signaling, and hard tissue mineralization. Therefore, the control of phosphorus balance is critical in all living organisms, and the fibroblast growth factor 23 (FGF23)-αKlotho system is central to maintain phosphate homeostasis in mammals. Although phosphate is indispensable for basic cellular functions, its excessive retention is toxic and can affect almost all organ systems' functionality. In human patients, hyperphosphatemia has been implicated in an increase in morbidity and mortality. Also, mouse models with hyperphosphatemia generated by disruption of the FGF23-αKlotho system exhibit extensive tissue damage, premature aging, and a short lifespan. Experimental studies using cell and animal models suggest that cytotoxic and inflammatory effects of elevated phosphate are partly mediated by abnormal cell signaling and oxidative stress. This review provides an overview of our current understanding regarding the toxicity of phosphate.

Antimicrobial drug resistance, partly due to inappropriate use of antimicrobials, is a global health problem that causes high morbidity and mortality and inflicts enormous economic burden worldwide...

There is a growing body of evidence for the effects of vitamin D on intestinal host-microbiome interactions related to gut dysbiosis and bowel inflammation. This brief review highlights the potential links between vitamin D and gut health, emphasizing the role of vitamin D in microbiological and immunological mechanisms of inflammatory bowel diseases. A comprehensive literature search was carried out in PubMed and Google Scholar using combinations of keywords "vitamin D," "intestines," "gut microflora," "bowel inflammation". Only articles published in English and related to the study topic are included in the review. We discuss how vitamin D (a) modulates intestinal microbiome function, (b) controls antimicrobial peptide expression, and (c) has a protective effect on epithelial barriers in the gut mucosa. Vitamin D and its nuclear receptor (VDR) regulate intestinal barrier integrity, and control innate and adaptive immunity in the gut. Metabolites from the gut microbiota may also regulate expression of VDR, while vitamin D may influence the gut microbiota and exert anti-inflammatory and immune-modulating effects. The underlying mechanism of vitamin D in the pathogenesis of bowel diseases is not fully understood, but maintaining an optimal vitamin D status appears to be beneficial for gut health. Future studies will shed light on the molecular mechanisms through which vitamin D and VDR interactions affect intestinal mucosal immunity, pathogen invasion, symbiont colonization, and antimicrobial peptide expression.

The consumption of sugar-sweetened beverages is a known contributory factor of childhood obesity that is documented around the globe. More importantly, reducing the consumption of sugar-sweetened beverages could reduce weight gain among overweight or obese children. Although sugar is present in many natural foods, artificial sugar is added into sugar-sweetened beverages, which has little or no nutritional value. However, the calories obtained from the sugar-sweetened beverages are linked to overweight and obesity, and an increase serving sizes of sugar-sweetened beverages over the years partly contributed to the alarming rise of childhood obesity around the globe. The sugar-sweetened beverages not only contain a high amount of sugar, but also contain a high amount of phosphate, and the possibility exists for an enhancing dual adverse health effects of sugar and phosphate. Increasing health awareness and limiting marketing approaches targeted towards the younger population are essential to reduce long-term health burdens that are linked to the overconsumption of sugar-sweetened beverages.

TG-interacting factor 1 (TGIF1) exerts inhibitory effects on transforming growth factor-beta (TGF-β) signaling by suppressing Smad signaling pathway at multiple levels. TGIF1 activity is important for normal embryogenesis and organogenesis, yet its dysregulation can culminate in tumorigenesis. For instance, increased expression of TGIF1 correlates with poor prognosis in triple-negative breast cancer patients, and enforced expression of TGIF1 facilitates Wnt-driven mammary tumorigenesis, suggesting that TGIF1 might function as an oncoprotein. Quite surprisingly, TGIF1 has recently been shown to function as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC), possibly owing to its ability to antagonize the pro-malignant transcription factor Twist1. In this article, we will briefly elaborate on the biological and clinical significance of the unique tumor-suppressive function of TGIF1 and its functional interaction with Twist1 in the context of PDAC pathogenesis and progression.

The novel coronavirus, COVID-19 is now officially declared as a pandemic by the World Health Organization (WHO), and most parts of the world are taking drastic measures to restrict human movements to contain the infection. Like millions of others around the world, I am wondering, is there anything that could be done, other than keeping high personal hygiene, and be vigilant of symptoms, to reduce the chances of infection, or at least to reduce the burden of the disease. So far, the National and International health agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the WHO have provided clear guidelines for both preventive and treatment suggestions. In this opinion-based article, I want to discuss, why keeping the adequate micronutrient balance might enhance the host response and be protective of viral infections. A detailed in-depth discussion of various micronutrients is not the purpose of this article, I will mostly emphasize on the role of zinc in viral infection.

The impact of nutrition on immunity is an intense area of research. Malnutrition is linked to a higher risk of microbial infections, while severe infections usually lead to a nutritional imbalance in affected patients. The nutritional status has an impact on the severity of the ongoing SARS-CoV-2 infection. Studies conducted on small numbers of patients have shown the benefits of maintaining optimal vitamin (B12 and D) and mineral (zinc and magnesium) balance in reducing the intensity of COVID-19. Although consuming a balanced diet with a healthy lifestyle is always desirable, the importance of such practice is even more meaningful during the COVID-19 pandemic. Keeping an optimal balance of vitamins and minerals through healthy dietary habits helps to maintain a robust immune system that is essential to combat invading microbial pathogens, including SARS-CoV-2.