Medicine and Pharmacology

Abstract: Chronic pain arises from complex interactions between peripheral and central nervous system structures that process nociceptive information and integrate it with sensory, autonomic, endocrine, emotional, and cognitive functions. Numerous neuroactive substances, including classical neurotransmitters, neuropeptides, hormones, neurotrophic factors, endocannabinoids, and endogenous opioids, participate in these processes. These substances are produced by specific anatomical structures and, in turn, act upon the same or other structures, thereby creating highly interconnected networks of reciprocal modulation. This review examines the actions of individual neuromodulators on pain-related anatomical structures throughout the nervous system, including primary afferents, spinal cord circuits, brainstem nuclei, hypothalamic systems, basal ganglia, limbic structures, and cortical regions. Particular emphasis is placed on the divergence of modulator actions, whereby a single substance influences multiple neural structures and functions, and on the converse principle of convergence, according to which individual structures receive inputs from numerous modulatory systems. The review covers hypothalamic hormones and peptides, monoamines, neuropeptides, neurotrophic factors, ion channels, and major excitatory and inhibitory neurotransmitter systems. The available evidence indicates that chronic pain is associated with widespread alterations in many anatomical and functional structures, although such changes do not necessarily constitute the primary cause of chronic pain. Instead, pain states emerge from dynamic interactions among multiple neuronal populations, signaling molecules, and physiological systems whose contributions vary according to disease state, internal bodily conditions, and environmental influences. By emphasizing both the divergence and convergence of neuromodulatory actions, this review highlights the extraordinary complexity of nociceptive networks and argues that chronic pain cannot be adequately explained by single mechanisms or isolated “key” processes. Rather, chronic pain appears to arise from the collective behavior of highly interconnected and adaptive neural systems.

Abstract: Introduction: The superficial palmar branch of the radial artery (SPBRA) typically originates 10 to 20 mm proximal to the distal wrist crease, before the radial artery winds around the carpal bones toward the dorsum of the hand. From its origin, the SPBRA courses along the palmar aspect of the hand, traverses the fibers of the thenar muscles, and anastomoses with the ulnar artery to form the superficial palmar arch. Anatomical variations of this branch are described in the literature; given its potential as a vascular pedicle for thenar flaps in the reconstruction of distal finger and hand injuries, knowledge of its morphology is indispensable for surgical safety. Objective: To report a proximal origin of the SPBRA and discuss its possible clinical and surgical implications. Case Report: During routine dissection, an anatomical variation in the origin of the SPBRA was identified in a right forearm disarticulated at the elbow level. The radial artery followed its usual course in the anterior forearm until it prematurely emitted the SPBRA in the distal third, 61.05 mm proximal to the wrist joint, characterizing a high origin compared to the pattern described in the literature. The branch directed itself obliquely in a distal and medial direction, penetrated the fibers of the abductor pollicis brevis muscle, and, after this intramuscular segment, anastomosed with the ulnar artery to form the superficial palmar arch. The total length of the SPBRA was 92.68 mm. Conclusion: The high origin of the SPBRA is a rare anatomical variation of great clinical relevance, the recognition of which is fundamental in planning surgical and reconstructive procedures of the hand, especially in the design of thenar flaps. In addition to corroborating previous literature findings, the present study contributes an unprecedented measurement of the distance between the high origin of the branch and the wrist joint, providing relevant data for the anatomical characterization of this variation.

Abstract: Background/Objectives: The supraclavicular foramen (SCF) is a rare anatomical variant formed when a branch of the supraclavicular nerve traverses the clavicle through a complete transclavicular canal. Published studies differ substantially in study material, denominators, and reporting of side-specific and bilateral data, so bilateral anatomy is often synthesized as if pairing were irrelevant. This study aimed to describe SCF in a Greek osteological sample and to apply a meta-analytic framework distinguishing per-clavicle prevalence, marginal laterality, paired laterality, and separately observed bilateral prevalence. Methods: We examined 115 dry clavicles of Greek origin for SCF frequency, size, and topography. Measurements were obtained independently by two observers using stainless-steel wires and digital calipers, with inter-rater agreement assessed by intraclass correlation coefficients. A systematic review and meta-analysis were then conducted according to PRISMA 2020. Quantitative synthesis included pooled per-clavicle prevalence, conventional marginal left-versus-right comparison, and feasibility-based paired laterality analysis under explicit dependence assumptions when bilateral information was incomplete. Observed bilateral prevalence was analyzed separately using only studies with directly reported body-level bilateral counts. Study quality was assessed using AQUA and CATAM. Results: Complete transclavicular canals, identified by paired supraclavicular foramina representing entrance and exit openings, were present in 3/115 clavicles (2.4%), with a mean patency diameter of 1.5 ± 0.8 mm and a mean relative acromial position of 0.44 ± 0.12. Inter-rater reliability was excellent. Pooled per-clavicle prevalence was 2.2% (95% CI: 1.4–3.0%; I² = 71%). Conventional marginal laterality showed significant left-sided predominance (OR = 1.76, 95% CI: 1.16–2.66; I² = 0%), while feasibility-based paired laterality yielded a stronger effect (paired OR = 2.26, 95% CI: 1.30–3.94). The main observed bilateral-prevalence model yielded 0.95% (95% CI: 0.33–2.70%). Minor small-study effects were suggested by the Doi/LFK framework. Conclusions: SCF is an uncommon developmental variant with consistent left-sided predominance. Bilateral anatomical variants should not be synthesized as if all observations were unpaired; separating per-clavicle prevalence, marginal laterality, paired laterality, and observed bilateral prevalence provides a more transparent and biologically meaningful synthesis.

Abstract: The proven involvement of sinuvertebral nerve (SVN) in discogenic low-back pain and the demonstration that its blockade has been effective in reducing the intensity and frequency of diffuse low back pain have led to an increase in publications related to the characterization of this nerve. However, there is a huge disparity in the observations resulting from the studies carried out, probably due to the technical difficulty of accessing this structure. In the last years the number of studies in large samples has increased but some important data in relation to nature of sinuvertebral nerve remain unpublished. We studied 100 vertebral column segments between L1 and L5, corresponding to both sides of 10 adult cadavers donated to the Body Donation Center and Dissection Rooms of the Complutense University of Madrid. All levels were carefully dissected to study sinuvertebral nerve origins and some samples of SVN were selected to routinely paraffin-embedded and serially sectioned with a Minot-type microtome at a 7µm thickness. Immediately after dewaxing following the standard histology lab protocols, sections from selected SVN (well-preserved morphology and histologic condition) were subjected to an immunohistochemical protocol to detect CGRP-IH, and VIP-IH. Data analysis was performed using IBM SPSS Statistics version 27 and RStudio. The SVN was observed with a single branch (pattern I) in 82 cases (85.4%) and with two branches (pattern II) at the same level in 14 cases (14.6%).Statistical differences were not found in relation to vertebral levels, side or sex. All sinuvertebral nerve samples that underwent immunohistochemical study were positive for CGRP and VIP, demonstrating the sympathetic nature of the nerve (VIP+) and its nociceptive component (CGRP+). This study confirms the neurochemistry profile of the SVN thanks due to the realization of the immunochemistry characterization directly in the SVN, not in its innervated structures. This information supports the usage of the SVN blocking from a pathophysiological point of view for diagnostic and treatment techniques (e.g., Percutaneous Transforaminal Endoscopic Radiofrequency Ablation of the SVN) in discogenic lumbar pain.

Abstract: The cavernous sinus remains one of the most anatomically complex and surgically challenging regions of the skull base because of its intimate relationships with the internal carotid artery and multiple cranial nerves. Detailed microsurgical anatomical knowledge is essential for safe skull base and parasellar surgery. A stepwise microsurgical cadaveric dissection of the cavernous sinus was performed on six adult formalinfixed specimens using a standard pterional extradural approach under magnification with a Leica operating microscope. Progressive extradural and interdural dissections were carried out to expose the lateral wall of the cavernous sinus, cranial nerves III, IV, V1, V2, and VI, the intracavernous internal carotid artery, and the principal surgical triangles of the cavernous sinus. The dissection demonstrated the multilayered interdural architecture of the lateral wall and allowed identification of the interdural cleavage plane extending from the superior orbital fissure to Meckel’s cave. Cranial nerves III, IV, V1, and V2 were identified within the lateral wall, whereas the abducens nerve coursed medially within the venous compartment adjacent to the cavernous internal carotid artery. Parkinson’s triangle and the anteromedial and infratrochlear corridors provided useful operative windows to the intracavernous compartment. Stepwise cadaveric dissection remains an effective educational tool for understanding the microsurgical anatomy of the cavernous sinus and improving operative orientation during skull base procedures.

Abstract: Anabolic-androgenic steroids (AAS), such as ND, are commonly used to enhance physical performance and muscle mass. However, its abuse has been associated with numerous adverse health effects, particularly on the hippocampus, affecting learning, working memory, and cognitive functions. The current study aims to investigate the potential effects of ND, aerobic exercise, resistance exercise, and the combination of ND with aerobic or resistance exercise on memory and cognitive functions. Moreover, the study aims to explore the possible underlying mechanisms of changes in memory and cognitive function. Adult male rats were divided into four groups: control (GI), only ND-treated (GII), only exercise (GIIIa & GIIIb), and combined exercise + ND-treated (GIVa & GIVb). Exercise included aerobic treadmill training and ladder-climbing modalities for 8 weeks, either alone or with ND. Cognitive function was evaluated using the Modified Barnes Maze and T-maze tests. Hippocampal integrity was assessed through oxidative stress markers, serum brain-derived neurotrophic factor (BDNF) levels, hippocampal nerve growth factor (NGF) expression, and histological examination. ND significantly impaired spatial learning and memory, increased oxidative stress, lowered serum BDNF levels, and reduced NGF expression in the hippocampus. Exercise markedly attenuated these harmful effects. Aerobic exercise gave the most pronounced improvements. It restored cognitive function, enhanced antioxidant defenses, increased serum BDNF levels, increased hippocampal NGF expression, and preserved hippocampal structure. Resistance training also had neuroprotective effects, but to a lesser extent than aerobic exercise. In brief, both aerobic and anaerobic exercise have been shown to exert protective effects against ND-induced neurotoxicity by enhancing antioxidant defenses and promoting neuronal integrity. The monitored neuroprotective benefits suggest that physical exercise could serve as a possible non-pharmacological approach to prevent or decrease cognitive impairments associated with anabolic steroid abuse.

Abstract: Objective: To study the effect of weight loss on the levels of vaspin, insulin, lipid profile and anthropometric indices in obese females participating in a low-energy dietary regimen combined with aerobic exercise. Materials and methods: This prospective observational study included 256 adult females aged (20-50) years were divided into 192 obese females with BMI ≥30 kg/m² and 64 normal weight females, with BMI 18.5-24.9 kg/m² as obese and control group respectively. The obese females were subgroups based on duration of dietary regimen as: Group I (3 months), Group II (6 months), and Group III (> 6 months). Each group consisted of 64 obese females and followed a low-calorie diet of 1200 to 1500 calories/day, combined with aerobic exercise training for 30 min/day all over the study period. Body mass index and waist circumference were measured post-weight loss. Serum vaspin, insulin, glucose levels, and lipid profiles were measured and analyzed statistically. Results: Baseline comparison revealed that body weight, waist circumference, BMI, vaspin, insulin, glucose, triglycerides, total cholesterol, and LDL of obese group were significantly increased compared to controls (P ≤ 0.05). Low-energy diet and aerobic exercise led to significant decrease in body weight, waist circumference, BMI, vaspin, insulin, glucose, especially with longer period of dietary regimen. Lipid profile showed improvement attitude but without statistical significance. BMI was positively correlated with most studied parameters and negatively correlated with HDL. Conclusions: Low-calorie diet accompanied with aerobic exercise were associated with body mass index, vaspin, insulin, and lipid profile level. Dieting and weight reduction, especially in longer periods, particularly for six months or more than six months, appear to normalize these parameters toward control values and improve metabolic status.

Abstract: Objective: Thyroid cartilage calcification and glucose metabolism may vary with age and gender. This study aimed to investigate the role of [18F]-sodium fluoride ([18F]NaF) and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT for the evaluation of physiological molecular calcification and glucose metabolism of thyroid cartilage with age. Methods: This retrospective study analyzed [18F]NaF and [¹⁸F]FDG PET/CT images from the CAMONA study (NCT01724749). Regions of interest were placed around the thyroid cartilage on CT images using OsiriX software. The mean standardized uptake value (SUVmean) was measured for [¹⁸F]NaF and [¹⁸F]FDG PET/CT images. Pearson correlation coefficients were calculated to evaluate the effects of aging on the uptake of [¹⁸F]NaF and ^[18F]FDG in the thyroid cartilage. Results: A total of 127 healthy subjects (65 females and 62 males) with a mean age of 48.46±14.13 (range 21–75) years for [¹⁸F]NaF PET/CT and a total of 114 healthy subjects (52 females and 63 males) with a mean age of 49.05±14.29 (range 21–75) years for [¹⁸F]FDG PET/CT were included. A significant positive correlation was observed between age and SUVmean of [¹⁸F]NaF in the thyroid cartilage (r=0.18, p=0.04). This result indicates that molecular calcification of this cartilage increases with aging. However, the correlation between age and SUVmean of [¹⁸F]FDG in the thyroid cartilage was not statistically significant (r=-0.09 p=0.31). Conclusion: This study presents a novel methodology for the determination of molecular calcification and glucose metabolism of laryngeal cartilage using [¹⁸F]NaF and [¹⁸F]FDG PET/CT. Molecular calcification of thyroid cartilage was found to increase with age, whereas glucose metabolism did not show a statistically significant correlation with age.

Abstract: The heel-strike (HS) paradigm of human gait originates from 19th-century chronophotographic studies conducted on Georges Demeny, a gymnasium instructor whose performed, exaggerated gait was never representative of natural locomotion. A compounding martial bias further normalised HS through military marching drill. A multi-disciplinary convergent argument analysis is conducted, integrating philological, zoological, anatomical, biomechanical, neurological and socioeconomic lines of evidence. All seven lines of argument support a forefoot-first model in which the centre of mass (CoM) leads the movement, stabilisers control equilibrium proactively, and the Triceps surae works in continuous eccentric mode---its natural functional state. Heel-strike generates impact forces up to 700 N with an ascending braking vector, under-recruits Gluteus maximus, progressively impoverishes plantar mechanoreceptors, and transmits repeated microtraumatic impulses up to the brain. Natural human gait is organised around forefoot contact, progressive CoM advance, and continuous eccentric stabiliser activity. The proposed model rediscovers lightness: a dance with gravity rather than a war against it. The HS paradigm is a culturally conditioned artefact with measurable pathological consequences.

Abstract: Traumatic tracheal injuries and congenital defects can be life threatening. Regenerating the trachea through tissue engineered scaffolds has emerged as an innovative alternative to traditional therapies. At present time, challenges in tracheal regeneration preclude clinical adoption, such as revascularization and promotion of favorable paracrine and immune signaling responses. This review summarizes current advances in tracheal regeneration and highlights key biological and engineering barriers to address to achieve functional tracheal regeneration.

Abstract: Background: The expanding interest of chatbots within the medical domain underscores the imperative for a comprehensive understanding of their capabilities and limitations, particularly in the context of anatomical education. Chatbots possess the potential to comprehend intricate anatomical concepts, deliver both advanced and contextually relevant information, and could serve as a valuable resource for medical students and educators. This study aimed to evaluate the proficiency and constraints of chatbots in the domain of neuroanatomy. Methods: We developed 30 questions and administered them to ChatGPT-4, Google Gemini, Microsoft Copilot, and Perplexity.ai, in their open versions. Questions were collaboratively constructed by the research team, selected through a semi-randomized process within the domain of neuroanatomy. Chatbots' responses were evaluated in a blinded manner for validity and appropriateness, utilizing a 5-point Likert scale. Results: The optimal performance was exhibited by ChatGPT-4 and Perplexity.ai, which achieved scores of 4.6 ± 0.5 and 4.5 ± 0.5, respectively. Microsoft Copilot (4.4 ± 0.5) and Google Gemini (4.1 ± 1.0) followed. The least successful performance was observed in the task of generating a neuroanatomical structure: only Microsoft Copilot attempted to fulfill the request, albeit with a dramatically flawed outcome. Conversely, Google Gemini and Perplexity.ai provided web links to anatomical illustrations. Conclusions: Despite technological advancements, AI models have not yet reached a level of sophistication sufficient to entirely supplant the role of educators or facilitators in a neuroanatomy course; however, they can serve as valuable adjunct tools for medical educators and students when utilized with careful consideration.

Abstract: The human microbiota is a diverse and dynamic ecosystem of microorganisms that inhabit the gastrointestinal tract and other body sites, playing a central role in host physiology. Microbial composition and density vary along the gastrointestinal tract, with the oral cavity and colon representing regions of highest diversity and microbial load, respectively. Beyond bacteria, gut virome and archaeome contribute to ecosystem stability and metabolic cooperation. The microbiota performs essential physiological functions, including maintenance of the intestinal barrier, modulation of the immune system, fermentation of dietary components into short-chain fatty acids (SCFAs), vitamin biosynthesis, and regulation of systemic metabolic and neuroendocrine pathways. Host–microbiota communication is mediated by microbial metabolites, pattern recognition receptors, immune cells, and neuroimmune interactions involving the enteric nervous system, forming the basis of the gut–brain, gut–liver, and other organ axes. Dysbiosis, caused by stress, aging, antibiotics, or an unhealthy diet, disrupts these interactions, contributing to inflammatory, metabolic, and neurodegenerative disorders. Environmental factors, including diet, physical activity, and sleep, profoundly shaped microbial composition and functional output. Diets rich in fiber, plant-based foods, and Mediterranean patterns promote microbial diversity and SCFA production, whereas Western diets predispose dysbiosis and systemic inflammation. Understanding the mechanisms by which microbiota influences host physiology provides opportunities for targeted interventions, including probiotics, prebiotics, and lifestyle modifications, aimed at restoring microbial balance and improving health outcomes. This review integrates current knowledge on the composition, function, and modulators of the human microbiota, emphasizing its central role in maintaining intestinal and systemic homeostasis across the lifespan.

Abstract: Background/Objectives: Wound healing is a complex biological process involving co-ordinated interactions among inflammatory cells, growth factors, extracellular matrix components, and resident tissue cells. Despite significant advances in experimental research, translation of these findings into clinical practice remains limited, partly due to the lack of reproducible and ethically accessible human wound models. Pilonidal disease, a chronic inflammatory condition of the sacrococcygeal region, is frequently treated by surgical excision with healing by secondary intention. The resulting open wound provides a unique opportunity to study the natural progression of human tissue repair. Methods: This narrative review examines current knowledge on wound-healing phys-iology, commonly used experimental wound models, and clinical studies related to pi-lonidal disease. Evidence from experimental, translational, and clinical literature was evaluated to explore the potential of open pilonidal excision wounds as a standardized human model for wound-healing research. Results: Following open excision, healing typically occurs within 4–10 weeks through the classical phases of inflammation, pro-liferation, and tissue remodeling. During this period, the wound remains externally accessible, allowing repeated clinical observation and serial collection of tissue samples, wound fluid, and exudate. This accessibility facilitates investigation of key biological processes, including angiogenesis, fibroblast proliferation, epithelial migration, cyto-kine signaling, and extracellular matrix remodeling. Compared with in vitro systems and animal models, the open pilonidal wound offers direct insight into human wound biology under clinically relevant conditions. Conclusions: Open pilonidal excision wounds constitute a reproducible and ethically feasible in vivo human model for translational wound-healing research. This model may support biomarker discovery and contribute to the development of new therapeutic strategies for impaired healing and chronic wounds

Abstract: Aging is a chronic, destructive process characterized by the progressive breakdown of the body, leading to a loss of control over homeostasis. Scientific evidence indicates that energy dysmetabolism, particularly the loss of regulation in glucose-dependent metabolic processes, significantly contributes to the aging process. In healthy individuals, glucose levels are tightly regulated, enabling optimal adaptation to the body's physiological demands. However, as glucose metabolism declines with age, it leads to pathological changes in cellular and tissue function, which in turn results in chronic inflammation that can further accelerate aging. In this narrative review, I examine the complex and multifaceted aspects of aging, which are driven by age-related and irreversible changes in cellular and tissue structure and function. These alterations directly affect brain function, the primary regulator of vital bodily processes. The age-related structural and functional changes observed in long-lived cells, especially neurons, cardiomyocytes, and osteocytes, significantly impact both the quality and longevity of life. Research aimed at improving glucose metabolism by supplementing nicotinamide adenine dinucleotide (NAD) precursors shows promise for enhancing both the quality and length of life.

Abstract: Anatomical variants are observed on paired body sides, yet many prevalence studies—particularly those based on osteological collections—report only right- and left-side frequencies without specifying whether findings occur bilaterally in the same individual. In such cases, the individual-level left–right structure is unobserved. Consequently, inference on laterality and bilateralism cannot be based on the reported data alone and must rely on explicit assumptions about within-individual dependence.We study this problem in the context of anatomic prevalence data, although the framework applies more broadly to paired binary outcomes. We parameterize the admissible joint distributions using a feasibility-based dependence index, λ, spanning the full range from independence to maximal feasible concordance implied by the marginal prevalences. Within this framework, we examine two complementary estimands: the paired odds ratio for laterality and bilateral prevalence.Analytic results and Monte Carlo simulations show that bilateral prevalence varies linearly and remains stable across the admissible dependence range, whereas the paired odds ratio exhibits intrinsic boundary instability as dependence approaches its feasible maximum due to vanishing discordant counts. Uncertainty-propagation analyses further indicate that laterality inference is robust to moderate misspecification of the dependence assumption. These results demonstrate that unobserved within-subject dependence is a structural inferential issue in paired binary meta-analysis and motivate feasibility-based sensitivity analysis when only marginal data are available.

Abstract: Ischemic heart disease remains the most significant cause of morbidity and mortality worldwide. Althoughconventional therapies such as β-blockers, ACE inhibitors, statins, and percutaneous coronary intervention havereduced mortality in industrialized nations, progress has plateaued, and global ischemic burden continues to rise.Renewed scientific attention has turned to canonical cardioprotective signaling pathways with a level of molecularprecision not previously feasible. Parallel advances in exercise biology and mesenchymal stem-cell derived exosome(MSC-EXO) research suggest an opportunity for integrative cardioprotection. Exercise, once understood primarilyin descriptive physiologic terms, is now recognized as a complex molecular stimulus that can activateredox-sensitive kinases, autophagy regulators, and metabolic remodeling pathways. New state-of-the-artinvestigations have gone towards decoding this “exercise secretome” and developing tools to modulate thesechemical cascades. Multiple experimental studies report that MSC-derived exosomes function as biologically activeparacrine vectors that deliver regulatory microRNAs and proteins to recipient cells and promote angiogenesis,suppress apoptosis, and support mitochondrial function. This narrative review assesses the effectiveness ofinterventions on canonical pathways such as ERK and AKT/mTOR on ISO-induced ischemic injury models to theheart based on recent animal and human studies. Supporting literature on stem cell biology, exosome deliverystrategies, and translational barriers is discussed to create an integrated framework that reinforces and sustainsreparative signaling in ISO-induced ischemic environments. Together, these two rapidly evolving fields, exercisebiology and MSC-ECO, may define the next frontier in regenerative ischemic cardiomyopathy by harnessing innaterepair pathways and bioengineered tools to potentiate the crosstalk among metabolic, kinase, and paracrine survivalcircuits.

Abstract: The centrosome, long recognized as the primary microtubule-organizing center (MTOC) of animal cells, is re-examined through the lens of information theory and systems biology. This preprint proposes a unifying hypothesis: the mother centriole within the centrosome acts as a non-genetic cellular ledger, a stable structural repository that accumulates molecular records of a cell’s replicative history and environmental exposures. These records—comprising specific post-translational modification (PTM) signatures, retained proteins, and structural alterations—are subsequently “read” by the cell to inform critical decisions regarding proliferation, differentiation, senescence, and apoptosis. We synthesize evidence from cell biology, gerontology, and evolutionary biology to construct the “Centrosomal Ledger Model.” This model positions the centriole not as a passive cytoskeletal component but as an active, heritable information-processing node that integrates temporal data across scales—from circadian rhythms to organismal aging. We detail the molecular mechanisms of information encoding (e.g., tubulin polyglutamylation, oxidative marks) and decoding (via ciliary signaling, proteostatic feedback, and mechanical transduction). The model’s implications challenge genetic determinism by highlighting structural inheritance, provides a material basis for cellular age, and offers novel, falsifiable avenues for experimental interrogation in aging and cancer research. Crucially, it suggests that modulating the “read-write” cycle of the centrosomal ledger could represent a new frontier in regenerative medicine.

Abstract: Although self-administered antigen tests are widely available, anatomical knowledge of nasal anatomy in the general population is limited. Cerebrospinal fluid leakage has been reported in multiple cases following damage to the roof of the nasal cavity due to accidental penetration of the cribriform plate of the ethmoid bone. Methods: Images of anatomical prosections used for teaching in the Dissection Room of the Faculty of Medicine of the University of Barcelona were obtained to illustrate the viable horizontal pathway to the nasopharynx through the inferior meatus, below the inferior turbinate. Screenshots from publicly available videos produced by the author demonstrating swab insertion were analyzed to measure the final insertion angle using 3D software. Publicly available instructions for patients included with authorized antigen tests in Spain were reviewed. Results: Antigen tests available in Spain in 2025 recommended a predominantly vertical swab insertion. However, successful horizontal insertion in the inferior meatus towards the nasopharynx can be achieved with a slight vertical angle of 7–9°. A schematic illustration for free use is provided. Conclusion: Swab instructions should be revised to emphasize an insertion perpendicular to the face in order to access the inferior meatus safely and reduce the risk of injury to the ethmoidal cells.

Abstract: Hypoxic pulmonary vasoconstriction (HPV) is a rapid and reversible constrictor response of the pulmonary vasculature, and especially its small muscular precapillary arteries, which is initiated by episodes of local alveolar hypoxia. Acting as a protective homeostatic vasomotor mechanism, HPV enables maximal gas exchange by diverting blood from poorly ventilated alveoli in to those rich in oxygen, thereby optimizing oxygen uptake and the ventilation-perfusion (V/Q) ratio so as to maintain the arterial oxygen partial pressure (P_aO₂) within the physiological range. HPV is an intrinsic mechanism of pulmonary artery smooth muscle cells (PASMC), and requires an O₂ sensor which acts through mediator(s) to trigger effector mechanisms within these cells to evoke constriction. Whereas HPV effector mechanisms are reasonably well-defined, the nature of the O₂ sensor and mediators remain in dispute. The three most comprehensive models of O2 sensing in HPV share a focus on the concept that hypoxia activates effector mechanisms by inducing a change in the PASMC cytoplasmic redox state. According to the Redox Theory, first proposed by Kenneth Weir and Stephen Archer in 1995, hypoxia inhibits mitochondrial production of reactive oxygen species (ROS), thereby causing the cytoplasm to become more reduced. This inhibits ongoing vasorelaxation maintained by the opening of voltage-gated K+ channels. In contrast, according to the Mitochondrial ROS hypothesis, introduced by Paul Schumacker and Naveen Chandel in 2001, hypoxia increases mitochondrial ROS production, causing an oxidizing shift in the cytoplasmic redox poise which activate several vasoconstricting pathways. In a third scenario, developed by Michael Wolin and Sachin Gupte, hypoxia evokes contraction by causing a fall in H2O2 production by NADPH oxidase, and by activating the pentose phosphate pathway. These effects inhibit basal vasorelaxation maintained by the guanylate cyclase and protein kinase G and also stimulate vasoconstricting mechanisms. In this comprehensive review, we summarize the key studies contributing to the development of these proposals and then subject the evidence supporting them to critical appraisal, based in part on how well they accord with the wider literature and recent developments in our understanding of how cells shape and deploy redox mechanisms in order to regulate cell function.

Abstract: Minimally invasive facial procedures are widely performed in clinical medicine but re-main associated with severe complications such as necrosis or blindness, often resulting from insufficient anatomical understanding and limited procedural training. To address these challenges, this study developed an anatomically accurate clinical simulator for fa-cial injection training. A three-dimensional polygonal facial model was constructed using standardized anatomical datasets reflecting skeletal dimensions, soft tissue characteris-tics and the average arterial distribution of East Asian faces. This model was integrated into simulation software connected to a facial silicone dummy with realistic tissue texture and an optical tracking system providing sub-millimeter precision. Each anatomical structure, including muscles, vessels and nerves, was digitally annotated and linked to interactive visualization tools. During training, the simulator simultaneously reflected the real-time needle trajectory and insertion depth; when the needle tip approached a high-risk structure, such as the supraorbital artery, alerts were automatically triggered. This feedback enabled trainees to recognize unsafe injection zones and adjust their tech-nique accordingly. The system provided a realistic, repeatable and safe environment for improving anatomical comprehension and procedural accuracy. This study proposes an innovative applied simulation system that may enhance medical education and clinical safety in facial injection procedures.