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The present communication examines the phenomenon of curfew in relation to the COVID-19 pandemic with special attention being laid on the management of the epidemic by Italian health authorities. A literature review and a historical–medical analysis were performed. A historical–medical excursus on the word curfew is offered and a comparison between military and health scenarios is given. Finally, this article stresses how words connected with wartime events should be contextualized when adopted in unmilitary scenarios such as pandemic emergencies and related public health responses.

The present study aims to approximate the face from the alleged skull of Jan Žižka (ca. AD 1360–1424), a military commander and national hero in the Czech Republic. Found in 1910, the skull has only a fraction of its original structure, which required an initial effort to reconstruct the missing regions from data collected in CT scans of living people’s heads. The forensic facial approximation consisted of projecting the skin boundaries with soft tissue markers and cross-referencing data from statistical projections from CT scans of living people and the use of the anatomical deformation technique, where the digital head of a virtual donor was adjusted until it matched the alleged skull of the Czech general. The final face was the result of the cross-referencing of all data and the completion of the structure respected the iconography attributed to Jan Žižka.

The primary factors that can be modified in one’s lifestyle are the most influential determinants and significant preventable causes of various types of cancer. Exercise has demonstrated numerous advantages in preventing cancer and aiding in its treatment. However, the precise mechanisms behind these effects are still not fully understood. To contribute to our comprehension of exercise’s impact on cancer immunotherapy and provide recommendations for future research in exercise oncology, we will examine the roles and underlying mechanisms of exercise on immune cells. In addition to reducing the likelihood of developing cancer, exercise can also improve the effectiveness of certain approved anticancer treatments, such as targeted therapy, immunotherapy, and radiotherapy. Exercise is a pivotal modulator of the immune response, and thus, it can play an emerging important role in new immunotherapies. The mechanisms responsible for these effects involve the regulation of intra-tumoral angiogenesis, myokines, adipokines, their associated pathways, cancer metabolism, and anticancer immunity. Our review assesses the potential of physical exercise as an adjuvant/neoadjuvant tool, reducing the burden of cancer relapse, and analyzes emerging molecular mechanisms predicting favorable adjuvanticity effects.

Background: Circulus arteriosus cerebri (CAC), responsible for supplying blood to the brain, presents anatomical variations that have been associated with both haemorrhagic and ischemic strokes. Therefore, it is crucial to conduct comprehensive investigations and comparisons of the diverse variant components of the CAC, published in various journals, and analyze them to identify individuals at risk of cerebrovascular pathologies, thereby ensuring enhanced and timely treatment. Methods: A scoping review according to the five-stage protocol by Arksey and O'Malley was performed between February and June 2023. Seven hundred and seventy-seven records were initially identified, and a total of 51 studies were finally included. Results: This scoping review focuses on the anatomical variations of the CAC and their clinical implications on cerebrovascular disease and includes more original articles than review s. Consistent with previous findings, most of the records included small populations or samples, while only three records reported larger populations. Surprisingly, the populations enclosed in the included records consisted of autopsied cadaveric specimens more than living subjects. Finally, the qualitative analysis highlighted three main themes concerning the relationship between the normal CAC morphology and the cerebrovascular disease onset as well as the variant CAC morphology and its main features that might be also involved in these diseases. Finally, techniques that can be used to measure CAC have also been assessed. Conclusion: Variations in the CAC, more common in the posterior part, with genetic and environmental factors influencing these variations impact cerebrovascular disorders. Understanding variants components of CAC can aid in improving brain surgeries and post-stroke care.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease leading to progressive demyelination and neuronal loss, with extensive neurological symptoms. As one of the most widespread neurodegenerative disorders, with an age onset of about 30 years, it turns out to be a socio-health and economic issue, thus necessitating therapeutic interventions currently unavailable. Loss of integrity in the blood–brain barrier (BBB) is one of the distinct MS hallmarks. Brain homeostasis is ensured by an endothelial cell-based monolayer at the interface between the central nervous system (CNS) and systemic bloodstream, acting as a selective barrier. MS results in enhanced barrier permeability, mainly due to the breakdown of tight (TJs) and adherens junctions (AJs) between endothelial cells. Specifically, proinflammatory mediator release causes failure in cytoplasmic exposure of junctions, resulting in compromised BBB integrity that enables blood cells to cross the barrier, establishing iron deposition and neuronal impairment. Cells with a compromised cytoskeletal protein network, fiber reorganization, and discontinuous junction structure can occur, resulting in BBB dysfunction. Recent investigations on spatial transcriptomics have proven circularRNAs (circRNAs) to be powerful multi-functional molecules able to epigenetically regulate transcription and structurally support proteins. In the present review, we provide an overview of the recent role ascribed to circRNAs in maintaining BBB integrity/permeability via cytoskeletal stability. Increased knowledge of the mechanisms responsible for impairment and circRNA’s role in driving BBB damage and dysfunction might be helpful for the recognition of novel therapeutic targets to overcome BBB damage and unrestrained neurodegeneration.

Migraine is one of the world’s most debilitating disorders, and it has recently been shown that changes in the retina can be a potential biomarker for the disease. These changes can be detected by optical coherence tomography (OCT), which measures retinal thickness, and optical coherence tomography angiography (OCTA), which measures vessel density. We searched the databases Google Scholar, ProQuest, Scopus, and Web of Science for studies in English using OCT and OCTA in migraineurs, using the search terms “optical coherence tomography,” “OCT,” “optical coherence tomography angiography,” “OCTA” and “migraine.” We found 73 primary studies, 11 reviews, and 8 meta-analyses pertaining to OCT and OCTA findings in migraineurs. They showed that migraineurs had reduced retinal thickness (via OCT), retinal vessel density, and greater foveal avascular zone area (via OCTA) than controls. OCTA changes reflect a perfusion compromise occurring in migraineurs as opposed to in healthy controls. OCT and OCTA deficits were worse in migraine-with-aura and chronic migraine than in migraine-without-aura and episodic migraine. Certain areas of the eye, such as the fovea, may be more vulnerable to these perfusion changes than other parts. Direct comparison between study findings is difficult because of the heterogeneity between the studies in terms of both methodology and analysis. Moreover, as almost all case–control studies were cross-sectional, more longitudinal cohort studies are needed to determine cause and effect between migraine pathophysiology and OCT/OCTA findings. Current evidence suggests both OCT and OCTA may serve as retinal markers for migraineurs, and further research in this field will hopefully enable us to better understand the vascular changes associated with migraine, perhaps also providing a new diagnostic and therapeutic biomarker.

Abstract Background Migraine is a common and distressing neurological condition characterised by recurrent throbbing headaches, nausea and heightened sensitivity to light and sound. Accumulating evidence suggests that cerebral arteries dilate during migraine, causing distal microvessels to constrict, which could activate nociceptors and cause onset of headache pain. If so, preventing or attenuating chronic microvascular constriction, and promoting a dilatory phenotype, may reduce frequency and/or severity of migraines. The primary aim of the L-Arginine and Aged Garlic Extract (LARGE) trial is to investigate whether oral treatment with dietary nutraceuticals, L-arginine and aged garlic extract (AGE), both systemic vasodilatory agents, will alleviate migraine frequency, duration and severity in adults with chronic frequent episodic migraines. Methods The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target sample is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention. Discussion The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated. Trial registration The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022.

Tuberculosis (TB) is an ancient chronic infectious disease that remains a global health concern. In human remains, the most common and characteristic clinical signs are the skeletal modifications involving the spine, such as in Pott’s disease. Diagnosing TB in ancient human remains is challenging. Therefore, in this systematic review, the authors investigated the studies assessing molecular diagnosis of Pott’s disease in ancient human remains with the intention to survey the literature, map the evidence, and identify gaps and future perspectives on TB in paleopathology. Our systematic review offers a full contextualization of the history of Pott’s disease in ancient times. Our search strategy was performed between August 2022 and March 2023. The authors initially identified 340 records, and 74 studies were finally included and assessed for qualitative analysis. Due to non-specific clinical signs associated with TB, how best to diagnose tuberculosis in human remains still represents a central point. Nevertheless, ancient DNA (aDNA) analysis, lipid biomarkers, and spoligotyping might be extremely useful tools in the study of TB in human remains. Moreover, we propose the extraction and study of immune response genes involved in innate and adaptive immunity versus Mycobacterium spp. as an innovative and vastly overlooked approach in TB paleopathology. Complementary methodologies should be integrated to provide the best approach to the study of TB in human remains.

The SARS-CoV-2 outbreak has infected a vast population across the world, causing more than 664 million cases and 6.7 million deaths by January 2023. Vaccination has been effective in reducing the most critical aftermath of this infection, but some issues are still present regarding re-infection prevention, effectiveness against variants, vaccine hesitancy and worldwide accessibility. Moreover, although several old and new antiviral drugs have been tested, we still lack robust and specific treatment modalities. It appears of utmost importance, facing this continuously growing pandemic, to focus on alternative practices grounded on firm scientific bases. In this article, we aim to outline a rigorous scientific background and propose complementary nutritional tools useful toward containment, and ultimately control, of SARS-CoV-2 infection. In particular, we review the mechanisms of viral entry and discuss the role of polyunsaturated fatty acids derived from α-linolenic acid and other nutrients in preventing the interaction of SARS-CoV-2 with its entry gateways. In a similar way, we analyze in detail the role of herbal-derived pharmacological compounds and specific microbial strains or microbial-derived polypeptides in the prevention of SARS-CoV-2 entry. In addition, we highlight the role of probiotics, nutrients and herbal-derived compounds in stimulating the immunity response.

Cardiovascular CT is being widely used in the diagnosis of cardiovascular disease due to the rapid technological advancements in CT scanning techniques. These advancements include the development of multi-slice CT, from early generation to the latest models, which has the capability of acquiring images with high spatial and temporal resolution. The recent emergence of photon-counting CT has further enhanced CT performance in clinical applications, providing improved spatial and contrast resolution. CT-derived fractional flow reserve is superior to standard CT-based anatomical assessment for the detection of lesion-specific myocardial ischemia. CT-derived 3D-printed patient-specific models are also superior to standard CT, offering advantages in terms of educational value, surgical planning, and the simulation of cardiovascular disease treatment, as well as enhancing doctor–patient communication. Three-dimensional visualization tools including virtual reality, augmented reality, and mixed reality are further advancing the clinical value of cardiovascular CT in cardiovascular disease. With the widespread use of artificial intelligence, machine learning, and deep learning in cardiovascular disease, the diagnostic performance of cardiovascular CT has significantly improved, with promising results being presented in terms of both disease diagnosis and prediction. This review article provides an overview of the applications of cardiovascular CT, covering its performance from the perspective of its diagnostic value based on traditional lumen assessment to the identification of vulnerable lesions for the prediction of disease outcomes with the use of these advanced technologies. The limitations and future prospects of these technologies are also discussed.

In the past few years, a renowned interest in the interplay between the immune system and central nervous systems (CNS) has sparked a wealth of new experimental studies. Two recent publications in Science shed new light on the “resident” immune cell populations in the CNS and their functions in homeostasis and pathological status, with potential implications in understanding CNS disease mechanisms and in designing new “intelligent” therapies.

Abstract This scoping review aims to perform a brief but comprehensive assessment of existing peer‐reviewed literature and determine whether raising nicotinamide adenine dinucleotide can prevent or promote tumorigenesis. The examination of extensive peer‐reviewed data regarding the synthesis of nicotinamide adenine dinucleotide has been performed with a focus on nuclear dynamics and the deoxyribose nucleic acid repair pathway. Various enzymatic protective functions have been identified from nicotinamide adenine dinucleotide levels, as well as the threat role that is also explored. Nicotinamide adenine dinucleotide precursors and sirtuin‐activating compounds are becoming ubiquitous in the commercial market. Further research into whether elevating levels of nicotinamide adenine dinucleotide or overexpression of sirtuins can increase the potential for neoplasm or other age‐related pathophysiology is warranted due to the high energy requirements of certain diseases such as cancer.

Abstract Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in every human cell and regulates a number of systems across multiple cellular compartments and tissue types via an endogenous and exogenous influence. NAD levels are demonstrated to decline with age and therefore measures to counteract the waning of NAD have been devised. A number of NAD precursor candidates such as nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), the reduced form of nicotinamide mononucleotide (NMNH), nicotinic acid (NA) nicotinamide (NAM), and dihydronicotinamide riboside (DNR) increase NAD levels in vitro and in vivo. This discussion will focus on the precursors NR, NMN, NMNH, and DNR in the upregulation of NAD. There are many publications on NAD precursors as it has become popular for human consumption in recent years due to its vital importance to the general consumer. However, there is no consensus between researchers and this was the aim of this review, to determine and discuss their areas of agreement versus disagreement, to highlight the gaps in research, and to give recommendations for future work. Bioavailability and potency of NR, NMNH, NMN, and DNR is also examined on the light of the most recent literature.

Physical exercise is considered an important physiological intervention able to prevent cardiovascular diseases, obesity, and obesity-related cardiometabolic imbalance. Nevertheless, basic molecular mechanisms that govern the metabolic benefits of physical exercise are poorly understood. Recent data unveil new mechanisms that potentially explain the link between exercise, feeding suppression, and obesity.

Prevention strategies should be constantly improved to manage falls and frailty in the elderly. Therefore, we aimed at creating a screening and predictive protocol as a replicable model in clinical settings. Bioimpedance analysis was conducted on fifty subjects (mean age 76.9 ± 3.69 years) to obtain body composition; then, posture was analysed with a stabilometric platform. Gait performance was recorded by a 10 m walking test, six-minute walking test, and timed up and go test. After 12 months, subjects were interviewed to check for fall events. Non-parametric analysis was used for comparisons between fallers and non-fallers and between able and frail subjects. ROC curves were obtained to identify the predictive value of falling risk and frailty. Path length (area under the curve, AUC = 0.678), sway area (AUC = 0.727), and sway speed (AUC = 0.778) resulted predictive factors of fall events (p < 0.05). The six-minute walking test predicted frailty condition (AUC = 0.840). Timed up and go test was predictive of both frailty (AUC = 0.702) and fall events (AUC = 0.681). Stabilometry and gait tests should be, therefore, included in a screening protocol for the elderly to prevent fall events and recognize the condition of frailty at an early stage.

There are approximately 1 billion prediabetic people worldwide, and the global cost for diabetes mellitus (DM) is estimated to be $825 billion. In regard to Type 1 DM, transplanting a whole pancreas or its islets has gained the attention of researchers in the last few decades. Recent studies showed that islet transplantation (ILT) containing insulin-producing β cells is the most notable advancement cure for Type 1 DM. However, this procedure has been hindered by shortage and lack of sufficient islet donors and the need for long-term immunosuppression of any potential graft rejection. The strategy of encapsulation may avoid the rejection of stem-cell-derived allogeneic islets or xenogeneic islets. This review article describes various biotechnology features in encapsulation-of-islet-cell therapy for humans, including the use of bile acids.

Anatomy has historically been a cornerstone in medical education regardless of nation, racial background, or medical school system. By learning gross anatomy, medical students get a first “impression” about the structure of the human body which is the basis for understanding pathologic and clinical problems. Gross anatomy classes are still regarded as an integral part of human biomedical education worldwide. Dissection of the human body is practiced in most anatomy institutions worldwide despite increasing pressure to reduce material and staff costs, regardless the ongoing debate concerning the suitability of body donors for medical education. Moreover, anatomical teaching skills are also evolving and need to be tailored for the different areas of anatomical expertise students have to acquire therefore, anatomic dissection goes probably beyond the scope of anatomy teaching in some classes such as sports sciences. However, there is no doubt that a practical approach to the study and teaching of anatomy is surely preferable to basic ex cathedra anatomy lectures. Here, we propose a brief insight into new teaching methods suitable for sports sciences students.

Atherosclerosis is a chronic autoimmune inflammatory disease that can cause coronary artery disease, stroke, peripheral artery disease, depending on which arteries are affected. At the beginning of atherosclerosis plasma lipoproteins accumulate in the sub-endothelial space. In response, monocytes migrate from the circulation through the endothelium into the intima where they differentiate into macrophages. These early events trigger a complex immune response that eventually involves many cellular subtypes of both innate and adaptive immunity. The Notch signaling pathway is an evolutionary conserved cell signaling system that mediates cell-to-cell communication. Recent studies have revealed that Notch modulate atherosclerosis by controlling macrophages polarization into M1 or M2 subtypes. Furthermore, it is known that Notch signaling controls differentiation and activity of T-helper and cytotoxic T-cells in inflammatory diseases. In this review, we will discuss the role of Notch in modulating immunity in the context of atherosclerosis and whether targeting Notch may represent a therapeutic strategy.

Reactive Oxygen Species (ROS) are molecules naturally produced by cells. If their levels are too high, the cellular antioxidant machinery intervenes to bring back their quantity to physiological conditions. Since aging often induces malfunctioning in this machinery, ROS are considered an effective cause of age-associated diseases. Exercise stimulates ROS production on one side, and the antioxidant systems on the other side. The effects of exercise on oxidative stress markers have been shown in blood, vascular tissue, brain, cardiac and skeletal muscle, both in young and aged people. However, the intensity and volume of exercise and the individual subject characteristics are important to envisage future strategies to adequately personalize the balance of the oxidant/antioxidant environment. Here, we reviewed the literature that deals with the effects of physical activity on redox balance in young and aged people, with insights into the molecular mechanisms involved. Although many molecular pathways are involved, we are still far from a comprehensive view of the mechanisms that stand behind the effects of physical activity during aging. Although we believe that future precision medicine will be able to transform exercise administration from wellness to targeted prevention, as yet we admit that the topic is still in its infancy.

Background: The bench press exercise (BP) is commonly practiced in both recreational and professional training. The weight is lowered from a position where the elbows are at a 90° angle at the start and

ObjectivesThe positive effects of spa therapy on ear, nose, and throat pathology are known but robust literature in this field, is still lacking. The aim of this study was to assess through a retrospective analysis, the effects on otitis media with effusion of Politzer endotympanic inhalation of sulphurous waters in children aged 5-9 years.MethodsA cohort of 95 patients was treated with Politzer insufflations of sulphurous water: 58 patients did a cycle consisting of a treatment of 12 days per year for three consecutive years; 37 patients followed the same procedure for 5 years consecutively. The control population was represented by untreated, age-matched children. A standard audiometric test was used before and after each cycle of treatment.ResultsOne cycle of Politzer inhalation of sulphur-rich water improved the symptoms. Three cycles definitively stabilized the improvement of hearing function.ConclusionOur results show that otitis media with effusion in children can be resolved by an appropriate non-pharmacological treatment of middle ear with sulphur-rich water.

BACKGROUND: Factors determining the shape of the human rib cage are not completely understood. We aimed to quantify the contribution of anthropometric and COPD-related changes to rib cage variability in adult cigarette smokers. METHODS: Rib cage diameters and areas (calculated from the inner surface of the rib cage) in 816 smokers with or without COPD, were evaluated at three anatomical levels using computed tomography (CT). CTs were analyzed with software, which allows quantification of total emphysema (emphysema%). The relationship between rib cage measurements and anthropometric factors, lung function indices, and %emphysema were tested using linear regression models. RESULTS: A model that included gender, age, BMI, emphysema%, forced expiratory volume in one second (FEV1)%, and forced vital capacity (FVC)% fit best with the rib cage measurements (R(2) = 64% for the rib cage area variation at the lower anatomical level). Gender had the biggest impact on rib cage diameter and area (105.3 cm(2); 95% CI: 111.7 to 98.8 for male lower area). Emphysema% was responsible for an increase in size of upper and middle CT areas (up to 5.4 cm(2); 95% CI: 3.0 to 7.8 for an emphysema increase of 5%). Lower rib cage areas decreased as FVC% decreased (5.1 cm(2); 95% CI: 2.5 to 7.6 for 10 percentage points of FVC variation). CONCLUSIONS: This study demonstrates that simple CT measurements can predict rib cage morphometric variability and also highlight relationships between rib cage morphometry and emphysema.

Anatomy has historically been a cornerstone in medical education regardless of nation, racial background, or medical school system. By learning gross anatomy, medical students get a first “impression” about the structure of the human body which is the basis for understanding pathologic and clinical problems. Although the importance of teaching anatomy to both undergraduate and postgraduate students remains undisputed, there is currently a relevant debate concerning methods of anatomy teaching. In the past century, dissection and lectures were its sole pedagogy worldwide. Recently, the time allocated for anatomy teaching was dramatically reduced to such an extent that some suggest that it has fallen below an adequate standard. Traditional anatomy education based on topographical structural anatomy taught in lectures and gross dissection classes has been replaced by a multiple range of study modules, including problem-based learning, plastic models or computer-assisted learning, and curricula integration. “Does the anatomical theatre still have a place in medical education?” And “what is the problem with anatomic specimens?” We endeavor to answer both of these questions and to contribute to the debate on the current situation in undergraduate and graduate anatomy education.