The Philippine Journal of Otolaryngology Head and Neck Surgerypreviously co published two guest editorials, on “Reducing the Risks of Nuclear War— the Role of Health Professionals”¹and “Time to Treat the Climate and Nature Crisis as One Indivisible Global Health Emergency”²that addressed dual potentially catastrophic concerns that both place us “on the brink.”³

By co-publishing these guest editorials, the Philippine Journal of Otolaryngology Head and Neck Surgery joined the call for “health professional associations to inform their members worldwide about the threat to human survival and to join with the International Physicians for the Prevention of Nuclear War (IPPNW) to support efforts to reduce the near-term risks of nuclear war.”¹As enumerated in the editorial,¹we urged three immediate steps that should be taken by nuclear-armed states and their allies: 1) adopt a no first use policy;⁴2) take their nuclear weapons off hair-trigger alert; and 3) urge all states involved in current conflicts to pledge publicly and unequivocally that they will not use nuclear weapons in these conflicts.It is alarming that noprogress has been made on these measures.

Thus, on our 44th Anniversary, we join over 150 scholarly scientific journals worldwide in co-publishing another Guest Editorial on “Ending Nuclear Weapons, Before They End Us.”⁵We call on the World Health Assembly (WHA) to vote this May on re establishing a mandate for the World Health Organization (WHO) to address the consequences of nuclear weapons and war,6and urge health professionals and their associations (including otolaryngologists – head and neck surgeons, all surgeons and physicians, and the Philippine Society of Otolaryngology – Head and Neck Surgery, Philippine College of Surgeons, Philippine College of Physicians,
Philippine Academy of Family Physicians, Philippine Pediatric Society, Philippine Obstetrical and Gynecologic Society, Philippine Society of Anesthesiology, Philippine College of Radiology, Philippine Society of Pathologists, other specialty and subspecialty societies, and the Philippine Medical Association) to urge the Philippine Government to support such a mandate and support the new United Nations (UN) comprehensive study on the effects of nuclear war.⁷

war ; armed conflicts ; Nuclear Energy ; Atomic Energy ; Radiation ; Nuclear Weapons

war ; Armed Conflicts ; Nuclear Energy ; Atomic Energy ; Radiation ; Nuclear Weapons

The Russian military invasion of Ukraine on February 24, 2022, and Hamas’ terror attack on Israel on October 7, 2023, signaled the beginning of two of the most recent wars to make international headlines. To date, over 110 armed conflicts are taking place: over 45 in the Middle East and North Africa (Cyprus, Egypt, Iraq, Israel, Libya, Morocco, Palestine, Syria, Turkey, Yemen, Western Sahara); over 35 in Africa (Burkina Faso, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Ethiopia, Mali, Mozambique, Nigeria, Senegal, Somalia, South Sudan, Sudan); 21 in Asia (Afghanistan, India, Myanmar, Pakistan, the Philippines); seven in Europe (Russia, Ukraine, Moldova, Georgia, Armenia, Azerbaijan); and six in Latin America (three each in Mexico and Colombia); with two more international armed conflicts (between India and Pakistan, and between India and China) in Asia.1 This list does not even include such problematic situations as those involving China and the South East Asia region. As though these situations of armed violence were not enough, mankind has already passed or is on the verge of passing several climate tipping points – a recent review lists nine Global core tipping elements (and their tipping points) - the Greenland Ice Sheet (collapse); West Antarctic Ice Sheet (collapse); Labrador-Irminger Seas / SPG Convection (collapse); East Antarctic Subglacial Basins (collapse); Amazon Rainforest (dieback); Boreal Permafrost (collapse); Atlantic M.O. Circulation (collapse); Arctic Winter Sea Ice (collapse); and East Antarctic Ice Sheet (collapse); and seven Regional impact tipping elements (and their tipping points) – Low-latitude Coral Reefs (die-off); Boreal Permafrost (abrupt thaw); Barents Sea Ice (abrupt loss); Mountain Glaciers (loss); Sahel and W. African Monsoon (greening); Boreal Forest (southern dieback); and Boreal Forest (northern expansion).2 Closer to home, how can we forget the disaster and devastation wrought by Super Typhoon Haiyan (Yolanda) 10 years ago to date? Whether international or non-international, armed conflicts raise the risk of nuclear war. Russia has already “rehearsed its ability to deliver a ‘massive’ nuclear strike,” conducting “practical launches of ballistic and cruise missiles,” and stationed a first batch of tactical nuclear weapons in Belarus,3 and the possibility of nuclear escalation in Ukraine cannot be overestimated.4 Meanwhile, in a rare public announcement, the U.S. Central Command revealed that an Ohio- class submarine (560 feet long, 18,750 tons submerged and carrying as many as 154 Tomahawk cruise missiles) had arrived in the Middle East on November 5, 2023.5 Indeed, “the danger is great and growing,” as “any use of nuclear weapons would be catastrophic for humanity.”
Armed Conflicts ; Nuclear Energy ; Radiation ; Climate Change ; Global Warming

Over 200 health journals call on the United Nations, political leaders, and health professionals to recognise that climate change and biodiversity loss are one indivisible crisis and must be tackled together to preserve health and avoid catastrophe. This overall environmental crisis is now so severe as to be a global health emergency.
Armed Conflicts ; Nuclear Energy ; Radiation ; Climate Change ; Global Warming

In January, 2023, the Science and Security Board of the Bulletin of the Atomic Scientists moved the hands of the Doomsday Clock forward to 90’s before midnight, reflecting the growing risk of nuclear war.1 In August, 2022, the UN Secretary-General António Guterres warned that the world is now in “a time of nuclear danger not seen since the height of the Cold War.2 The danger has been underlined by growing tensions between many nuclear armed states.1,3 As editors of health and medical journals worldwide, we call on health professionals to alert the public and our leaders to this major danger to public health and the essential life support systems of the planet—and urge action to prevent it.
Armed Conflicts ; Nuclear Energy ; Radiation

Diabetes is a widespread, rapidly increasing metabolic disease that is driven by hyperglycemia. Early glycemic control is of primary importance to avoid vascular complications including development of retinal disorders leading to blindness, end-stage renal disease, and accelerated atherosclerosis with a higher risk of myocardial infarction, stroke and limb amputations. Even after hyperglycemia has been brought under control, "metabolic memory," a cluster of irreversible metabolic changes that allow diabetes to progress, may persist depending on the duration of hyperglycemia. Manipulation of bile acid (BA) receptors and the BA pool have been shown to be useful in establishing glycemic control in diabetes due to their ability to regulate energy metabolism by binding and activating nuclear transcription factors such as farnesoid X receptor (FXR) in liver and intestine as well as the G-protein coupled receptor, TGR5, in enteroendocrine cells and pancreatic β-cells. The downstream targets of BA activated FXR, FGF15/21, are also important for glucose/insulin homeostasis. In this review we will discuss the effect of BAs on glucose and lipid metabolism and explore recent research on establishing glycemic control in diabetes through the manipulation of BAs and their receptors in the liver, intestine and pancreas, alteration of the enterohepatic circulation, bariatric surgery and alignment of circadian rhythms.
Animals ; Bile Acids and Salts ; blood ; metabolism ; Blood Glucose ; drug effects ; metabolism ; Circadian Rhythm ; Diabetes Mellitus ; blood ; drug therapy ; metabolism ; Energy Metabolism ; Homeostasis ; Humans ; Hyperglycemia ; metabolism ; physiopathology ; Hypoglycemic Agents ; therapeutic use ; Intestinal Mucosa ; metabolism ; Intestines ; drug effects ; Lipid Metabolism ; Liver ; drug effects ; metabolism ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Signal Transduction

BACKGROUND/OBJECTIVES: The study was conducted to evaluate the effects of dietary leucine supplementation on mitochondrial biogenesis and energy metabolism in the liver of normal birth weight (NBW) and intrauterine growth-retarded (IUGR) weanling piglets. MATERIALS/METHODS: A total of sixteen pairs of NBW and IUGR piglets from sixteen sows were selected according to their birth weight. At postnatal day 14, all piglets were weaned and fed either a control diet or a leucine-supplemented diet for 21 d. Thereafter, a 2 × 2 factorial experimental design was used. Each treatment consisted of eight replications with one piglet per replication. RESULTS: Compared with NBW piglets, IUGR piglets had a decreased (P < 0.05) hepatic adenosine triphosphate (ATP) content. Also, IUGR piglets exhibited reductions (P < 0.05) in the activities of hepatic mitochondrial pyruvate dehydrogenase (PDH), citrate synthase (CS), α-ketoglutarate dehydrogenase (α-KGDH), malate dehydrogenase (MDH), and complexes I and V, along with decreases (P < 0.05) in the concentration of mitochondrial DNA (mtDNA) and the protein expression of hepatic peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). Dietary leucine supplementation increased (P < 0.05) the content of ATP, and the activities of CS, α-KGDH, MDH, and complex V in the liver of piglets. Furthermore, compared to those fed a control diet, piglets given a leucine-supplemented diet exhibited increases (P < 0.05) in the mtDNA content and in the mRNA expressions of sirtuin 1, PGC-1α, nuclear respiratory factor 1, mitochondrial transcription factor A, and ATP synthase, H+ transporting, mitochondrial F1 complex, β polypeptide in liver. CONCLUSIONS: Dietary leucine supplementation may exert beneficial effects on mitochondrial biogenesis and energy metabolism in NBW and IUGR weanling piglets.
Adenosine Triphosphate ; Birth Weight* ; Citrate (si)-Synthase ; Diet ; DNA, Mitochondrial ; Energy Metabolism* ; Fetal Growth Retardation ; Leucine* ; Liver ; Malate Dehydrogenase ; Nuclear Respiratory Factor 1 ; Organelle Biogenesis* ; Oxidoreductases ; Parturition* ; Peroxisomes ; Pyruvic Acid ; Research Design ; RNA, Messenger ; Sirtuin 1 ; Transcription Factors

BACKGROUND: We are continually exposed to low-dose radiation (LDR) in the range 0.1 Gy from natural sources, medical devices, nuclear energy plants, and other industrial sources of ionizing radiation. There are three models for the biological mechanism of LDR: the linear no-threshold model, the hormetic model, and the threshold model. OBJECTIVE: We used keratinocytes as a model system to investigate the molecular genetic effects of LDR on epidermal cell differentiation. METHODS: To identify keratinocyte differentiation, we performed western blots using a specific antibody for involucrin, which is a precursor protein of the keratinocyte cornified envelope and a marker for keratinocyte terminal differentiation. We also performed quantitative polymerase chain reaction. We examined whether LDR induces changes in involucrin messenger RNA (mRNA) and protein levels in calcium-induced keratinocyte differentiation. RESULTS: Exposure of HaCaT cells to LDR (0.1 Gy) induced p21 expression. p21 is a key regulator that induces growth arrest and represses stemness, which accelerates keratinocyte differentiation. We correlated involucrin expression with keratinocyte differentiation, and examined the effects of LDR on involucrin levels and keratinocyte development. LDR significantly increased involucrin mRNA and protein levels during calcium-induced keratinocyte differentiation. CONCLUSION: These studies provide new evidence for the biological role of LDR, and identify the potential to utilize LDR to regulate or induce keratinocyte differentiation.
Blotting, Western ; Cell Differentiation ; Keratinocytes* ; Molecular Biology ; Nuclear Energy ; Polymerase Chain Reaction ; Radiation, Ionizing ; RNA, Messenger

In addition to DNA repair pathways, cells utilize translesion DNA synthesis (TLS) to bypass DNA lesions during replication. During TLS, Y-family DNA polymerase (Polη, Polκ, Polı and Rev1) inserts specific nucleotide opposite preferred DNA lesions, and then Polζ consisting of two subunits, Rev3 and Rev7, carries out primer extension. Here, we report the complex structures of Rev3-Rev7-Rev1(CTD) and Rev3-Rev7-Rev1(CTD)-Polκ(RIR). These two structures demonstrate that Rev1(CTD) contains separate binding sites for Polκ and Rev7. Our BIAcore experiments provide additional support for the notion that the interaction between Rev3 and Rev7 increases the affinity of Rev7 and Rev1. We also verified through FRET experiment that Rev1, Rev3, Rev7 and Polκ form a stable quaternary complex in vivo, thereby suggesting an efficient switching mechanism where the "inserter" polymerase can be immediately replaced by an "extender" polymerase within the same quaternary complex.
Binding Sites ; Crystallography, X-Ray ; DNA Repair ; DNA-Binding Proteins ; chemistry ; genetics ; metabolism ; DNA-Directed DNA Polymerase ; chemistry ; genetics ; metabolism ; Fluorescence Resonance Energy Transfer ; Humans ; Mad2 Proteins ; Nuclear Proteins ; chemistry ; genetics ; metabolism ; Nucleotidyltransferases ; chemistry ; genetics ; metabolism ; Protein Binding ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Proteins ; chemistry ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; chemistry ; genetics