The late 19th century witnessed a growing concern about the rising incidence of nervous disorders. Sociologists explained this with reference to the impacts of urbanisation, industrialisation and modernity. Medical practitioners identified psychological and physiological explanations for nervous disorders, focussing on a constellation of symptoms that became known as neurasthenia. While many commentators considered neurasthenia a condition of the middle classes, there was growing evidence that nervous disorders affected a wide range of the social spectrum, including the working class. We explore the prevalence of nervous disorders in the late 19th-century, using the British Post Office as a case study. We identify the significance of nervous disorders as a cause of sickness absence and of retirement, taking note of occupation and gender as key variables. We examine the contrasting explanations offered by management and workers for the incidence of nervous disorders, pointing to the significance of specific labour practices on different groups of workers. We compare our findings with those in other industries in the 20th century and conclude that similar rates of nervous disorders occurred across time and in different kinds of occupations. We conclude by suggesting that different working conditions were a significant factor in explaining the incidence of nervous disorders and that this needs to be taken into account by historians alongside more traditional explanations of nervousness based on social change and the impact of modernity on the human psyche.
Trees experience decades-to-centuries of environmental change within a single lifetime, requiring molecular mechanisms that enable rapid physiological and transcriptional adjustment without genetic adaptation across generations. Increasing drought frequency provides one important example of the environmental challenges faced by long-lived species. DNA methylation is a candidate regulator of such responses, but whether environmentally induced methylation primarily protects the genome, regulates nearby transcription, or both, remains an outstanding question. To address this question, we integrated methylome and transcriptome data from valley oak ( Quercus lobata ) seedlings exposed to drought and well-watered conditions. Drought conditions induced widespread and dynamic CHH methylation that repeatedly targeted the same gene-proximal transposable elements (TEs) across successive drought exposures despite turnover of individual methylated cytosines. This response was concentrated within specific TE families, indicating targeted recruitment of CHH methylation across the genome. Genes associated with CHH-methylated upstream TEs showed increased transcription under drought and were enriched for drought-response pathways, including abscisic acid signaling, cuticle and wax biosynthesis and cell wall remodelling. Nonetheless, the magnitude of transcriptional activation declined with increasing CHH methylation, indicating a graded regulatory effect rather than binary silencing. Despite little overall change in the TE transcriptome, greater CHH methylation was specifically associated with reduced expression of intragenic TEs, consistent with maintenance of local TE repression. These findings support a model in which repeated drought consistently recruits CHH methylation to reproducible gene-proximal TEs, where it is associated with maintenance of local TE repression despite continued activation of neighboring stress-responsive genes. Increasing CHH methylation is associated with progressively weaker transcriptional responses, suggesting that high levels of CHH methylation may simultaneously suppress TE activity and constrain nearby gene expression. Such a mechanism may influence how long-lived trees repeatedly adjust transcriptional responses to fluctuating climates throughout their lifespan. Genome protection during drought may carry an associated cost to stress-responsive gene expression.
Faunal extinctions correlate with human colonization worldwide during the Quaternary, yet the extent to which human hunting drove these losses remains debated. Resolving these debates depends on accurately dating both human arrival and animal extinction events. Herein I present a simulated overkill scenario modeling interaction between a founding human population and a single prey species. The simulation evaluates expected age offsets, the differences between the actual and observed dates, for extinction and colonization as functions of sample size and human population growth rate. Results show that when extinction is driven by human hunting, age offsets for extinction are expected to be smaller than those for colonization. This difference in age offset is expected because overkill produces a rapid demographic collapse of prey populations and taphonomic processes concentrate late-surviving individuals in the fossil record. In contrast, colonization dates are more offset because human populations are smallest immediately after arrival, and archaeological rarity is compounded by taphonomic effects. Although colonization age offsets are consistently larger than extinction age offsets across sample sizes, they are not extreme, such that archaeological sites should be detectable within five centuries of initial human settlement under modest rates of human population growth.
Pearl powder has been used for centuries in Traditional Chinese Medicine for its detoxifying, regenerative, and anti-aging properties. This study evaluates the antioxidant efficacy and safety of pearl powder derived from Hong Kong pearl oysters (Pinctada imbricata). The present study aimed to perform a comprehensive multiscale physicochemical characterization of pearl powder and to investigate it's in vivo antioxidant activity and subacute oral toxicity in C57BL/6J mice. The powder was characterized using Raman spectroscopy, high-resolution transmission electron microscopy (HR-TEM), atomic force microscopy (AFM), BET surface area analysis, and X-ray photoelectron spectroscopy (XPS). In vivo antioxidant activity was assessed in male C57BL/6J mice (n = 12 per group) administered pearl powder orally at 250, 500, and 1000 mg/kg body weight daily for 4 weeks using FRAP, TEAC, ORAC, and MDA assays. A 28-day subacute toxicity study was conducted according to OECD Guideline 407 (500-1000 mg/kg b.w., n=5/sex/group). Dose-dependent increases in FRAP, TEAC, and ORAC, together with reduced MDA levels, were observed especially in liver, kidney, and spleen (p < 0.05 to p < 0.0001). The toxicity study showed no mortality, clinical signs, or histopathological changes. Minor non-adverse biochemical variations lacked supporting pathology, establishing a No Observed Adverse Effect Level (NOAEL) of 500 mg/kg b.w. These findings demonstrate pearl powder's potent antioxidant activity with a favorable safety profile, supporting its development as a natural therapeutic agent for oxidative stress-related conditions. Nonetheless, confirmation through clinical studies will be important to substantiate these preclinical observations.
The use of urticating setae by tarantulas from the Americas and the Caribbean has been known for centuries and is considered a defensive behavior against vertebrate predators. However, their passive use against invertebrates, such as parasitic fly maggots and ants, has also been recently proposed, but no active use of these setae against invertebrates has been observed or tested. In this study, eight tarantula specimens representing four different species from the family Theraphosidae were tested in twelve tests with the army ant Eciton burchelli and the carpenter ant Camponotus rufipes. Four spiders interacted with Eciton burchelli, and one interacted with Camponotus rufipes. The defensive behavior was distinct from that used against vertebrates, as the spider rubs the lower posterolateral region of the abdomen with downward and outward movements of the hind legs and uses silk threads. Scanning electron microscopy (SEM) demonstrated that the ants were entangled with urticating setae, primarily of type I morphology. Type I urticating setae are found exclusively in an important clade of theraphosine spiders, the tribe Theraphosini, which includes the largest known spiders. It is hypothesized here that protection against predation by ants due to the emergence of a specific type of urticating seta may be one of the factors responsible for the success of tarantulas in the New World.
This article examines how engineers and surveyors transformed the management of the Po Valley environment between the sixteenth and eighteenth centuries. Drawing on archival registers, hydraulic reports, and technical manuals from the State of Milan, it argues that these professionals did not simply apply scientific knowledge to nature. Through practices of measurement, mapping, classification, and repair, they made water, woodlands, and agricultural land into governable resources. Engineers mediated conflicts over irrigation, assessed landed property, standardized environmental records, and linked hydraulic infrastructures to broader economic and political goals. Their work connected mathematics, mechanics, and natural knowledge to the everyday administration of one of Europe's most intensely managed agroecosystems. By foregrounding technical practice rather than scientific theory alone, the article shows how environmental governance emerged through routine acts of observation, calculation, and intervention.
Hydrocephalus is common with a mixed phenotype and aetiology. Its treatment is predominantly surgical, with temporary or permanent cerebrospinal fluid (CSF) diversion, which does not address the underlying disease mechanism. The choroid plexus (ChP), a secretory epithelium found in all four ventricles of the brain, produces most CSF within the central nervous system and has been investigated extensively over the past century to understand its function and potential role as a therapeutic target. Past attempts at either medically or surgically controlling its rate of secretion have not significantly altered our approach to the treatment of hydrocephalus, with CSF diversion remaining the main intervention. Rodent models of post-haemorrhagic hydrocephalus (PHH) have advanced our understanding of choroid plexus function in health and disease. Pre-clinical experiments have demonstrated a hypersecretory response in the ChP that may contribute to PHH. Targeting the choroid plexus directly may therefore present a novel therapeutic method. These findings have led to a significant increase in pre-clinical studies exploring this hypersecretory response and how to modulate it. Translating these promising results to clinical practice will rely on the development of large animal hydrocephalus models, which thus far has been limited. This literature review discusses the recent advances in targeting the ChP as a treatment for hydrocephalus, both surgically and non-surgically, and the current barriers to further advancement of this approach.
Recent mortality patterns reflect increasingly complex pathophysiological processes in which underlying causes (UCD) capture only part of the disease burden. The multi-cause approach offers an alternative because it allows analysis of diseases appearing in the lethal process both as consequences of the UCD and as contributory causes. In this paper, we use pattern-of-failure life tables to explicitly account for disease interdependence among all causes reported on the death certificate and remeasure the levels and trends in the disease burden in the U.S. during 2000-2021. Results show the largest discrepancies between underlying-cause and multiple-cause frameworks for heart disease, followed by other respiratory, mental, and metabolic disorders. Intermediate and immediate roles are dominated by other and acute respiratory conditions, heart disease, and infectious diseases, while contributory roles carry growing burdens from metabolic, mental, and heart conditions. Over the study period, heart disease recorded as the underlying cause declines even as its presence in other positions rises, underscoring its continuing importance in the lethal process. Cohorts born since 1960 exhibit increasing contributions of digestive and infectious diseases to mortality, and during the COVID-19 pandemic (2020-2021) notable distortions in role-specific disease burden are observed. In conclusion, the analysis provides context for trends based on underlying causes and offers a comprehensive analysis of evolution of mortality patterns by cause of death in the U.S. in the 21st century.
The interactions of pulmonary and renal physiology that underlie acute lung injury (ALI) and acute kidney injury (AKI) have been recognized for nearly a century. The understanding of lung-kidney crosstalk has evolved and is recognized as an important factor in patient management and outcomes. We aim to describe the association between fluid accumulation (FA) and ALI with outcomes of critically ill children and young adults requiring continuous renal replacement therapy (CRRT). Planned secondary analysis using data from the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK). ALI severity was defined using the Berlin oxygenation criteria. Fluid accumulation was categorized as ≤ 10%, > 10-20%, and > 20% at CRRT initiation. Illness severity was quantified using the Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2). The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included (1) 28-day mechanical ventilation (IMV) free days, (2) 28-day ICU free days, and (3) major adverse kidney events at 90 days (MAKE90) defined by death, persistent kidney dysfunction (eGFR reduction by 25% of baseline), or new dialysis requirement. This is a multinational retrospective cohort study. Invasively ventilated patients aged 0-25 years from January 2015 to December 2021 requiring CRRT for AKI or FA with ALI. There were no interventions. A total of 312 patients were included in the analysis. ALI was mild in 67 (21.5%), moderate in 142 (45.5%), and severe in 103 (33.0%). Fluid accumulation was ≤ 10% in 166 (53.2%), > 10-20% in 60 (19.2%), and > 20% in 86 (27.6%). The ICU mortality was 44.6% (139/312). In the multivariable analysis, neither ALI nor FA category was associated with mortality or MAKE90. Time to CRRT initiation (aOR 1.04, 95% CI 1.01-1.08) and illness severity (aOR 1.25, 95% CI 1.14-1.37) were associated with mortality.  In children and young adults with ALI receiving CRRT for AKI or FA, longer time to CRRT initiation and illness severity at CRRT initiation were associated with mortality. When accounting for multiple factors, neither ALI nor FA at CRRT initiation were associated with MAKE90 or mortality. Our findings warrant further exploration in a prospective cohort. • Acute kidney injury (AKI) and acute lung injury (ALI) commonly coexist in critically ill children and are associated with increased morbidity and mortality through bidirectional organ crosstalk. • Fluid accumulation (FA) worsens both AKI and ALI, with higher degrees of FA associated with worse outcomes, with continuous renal replacement therapy (CRRT) frequently used to manage the consequences of AKI and FA. • In this multicenter international cohort of children and young adults with ALI receiving CRRT, longer time to CRRT initiation and illness severity at CRRT initiation, but neither ALI nor FA at CRRT initiation were associated with mortality were associated with mortality. • These findings suggest that FA thresholds at the start of interventions may be less discriminatory in populations with dynamic processes such as severe multiple organ failure.
The blood-retinal barrier (BRB) consists of the inner and outer blood-retinal barrier (abbreviated as inner BRB and outer BRB). The inner and outer BRB's together regulate the transport of substances between the blood and neural retina via various membrane transporters. To utilize the oral administration for the pharmacotherapy of retinal diseases, it is necessary and important to understand many drug transport mechanisms in the BRB's. This review discusses the BRB transport research reported over more than a quarter of a century, particularly the development of in vitro and in vivo transport evaluation systems as well as newly discovered BRB-specific cationic drug transport mechanisms.
This article uses the global trade in Chinese egg products to rethink the history of refrigeration beyond narratives of technological diffusion and thermal colonialism. Tracing the rise of China's egg-processing industry in the treaty ports, it argues that refrigeration functioned not simply as a colonial technology but as an infrastructure through which states, firms, and consumers negotiated questions of hygiene, trust, and market power. British and American companies introduced refrigerated production systems that Chinese enterprises selectively adapted, while the rapid expansion of low-cost exports provoked protectionist campaigns and sanitary disputes in Europe and the United States. "Chinese eggs" became a political and cultural problem through which anxieties about industrial food, racial difference, and international competition were expressed. As export markets contracted during the interwar crisis of the twentieth century, refrigeration expanded into China's domestic economy through cold storage, logistics, and mass consumer culture. The article shows how refrigeration reshaped both global food politics and everyday urban life in modern China.
The question of whether acoustic radiation force is a consequence of linear or nonlinear wave fields has been debated for over a century. It is understood that the Rayleigh radiation pressure depends on the quadratic term in the equation of state, whereas the Langevin radiation pressure does not [R. T. Beyer, J. Acoust. Soc. Am. 63, 1025-1030 (1978)]. Nevertheless, traditional derivations of the Langevin radiation force begin with the nonlinear momentum equation. Here, the Langevin radiation force is derived from the linearized continuity, state, and momentum equations, proving that "for the calculation of the average force correct up to terms of the second order in the velocity, it is sufficient to find the solution of the linear scattering problem" [L. P. Gor'kov, Sov. Phys. Dokl. 6, 773-775 (1962)]. The linear origins of the Langevin radiation force are clarified by drawing parallels with radiation forces exerted by electromagnetic waves, surface gravity waves, and waves on a string.
We aimed to evaluate the role of medical therapy before and after balloon pulmonary angioplasty (BPA) for non-operable chronic thromboembolic pulmonary hypertension (CTEPH) in the modern management era. This Japanese nationwide, multicenter, prospective observational registry, including 37 centers, analyzed data newly registered from August 2018-December 2023. Pretreatment before BPA was analyzed in patients who were treatment naïve or received medical therapy only at registration (n = 557). De-escalation or escalation of medical therapy after BPA was analyzed in patients who underwent BPA (n = 966). The BPA pretreatment analysis in 557 patients showed that approximately 70% of the patients received medical therapy, of which 18% received combination therapy. Patients who received monotherapy or combination therapy had more severe baseline hemodynamics than those who did not. The 3-year survival did not significantly differ between the no, mono, and combination pretreatment groups (94%, 98%, and 97%, respectively; p = 0.852). The BPA post-treatment analysis in 966 patients showed that 20% of patients underwent de-escalation of medical therapy. Patients with de-escalation of medical therapy had lower mean pulmonary artery pressure (PAP) (20.9 ± 5.8 vs. 24.1 ± 7.3 mmHg, p < 0.01); however, they had a lower cardiac index at last follow-up compared to patients without de-escalation (2.66 ± 0.61 vs. 2.84 ± 0.70 L/min/m2, p = 0.01). Patients with severe disease tended to undergo pre-treatment before BPA; however, patient survival did not differ across pretreatment types. De-escalation of medical therapy after BPA can affect cardiac index. Therefore, de-escalation or continuation of medical therapy should be carefully considered even after mean PAP normalizes after BPA.
This article reviews the historical development and current challenges of pharmacy education in Japan, focusing on structural reform and the shift toward competency-based education. The 1992 revision of the Medical Care Act and the 1993 sorivudine incident heightened awareness of medication safety and accelerated expansion of pharmacists' clinical responsibilities, prompting educational reform. In 2006, a six-year pharmacy education program (6-YP) was introduced as the primary pathway to pharmacist licensure, while a four-year program (4-YP) was retained for research-oriented training. The Model Core Curriculum (MCC) standardized pharmacy education nationwide. The 2013 revision defined ten graduation-level competencies, reflecting an outcome-based framework. The 2022 MCC further reconceptualized competencies as capabilities that develop longitudinally across the professional lifespan and strengthened alignment with medical and dental education, public health perspectives, research literacy, and digital competencies. Pharmacist licensure in Japan is granted for life, and continuing education is not legally mandated. Although multiple voluntary certification systems promote advanced practice, variability among programs has raised concerns regarding transparency and standardization. Establishing a nationally coordinated continuing professional development framework and promoting lifelong competency development remain key priorities in response to technological innovation and evolving healthcare needs.
Diabetes is a dynamic disease, an ever-evolving entity. In existence for centuries, the prevalence of diabetes has increased manifold over the past few decades.1 This evolution is associated with a change in classification, clinical features, comorbidities, complications, and clinical management strategies. These changes are what we describe as the Darwinization of diabetes. Charles Darwin was one of the most important scientists in human history. His research forms the basis of evolutionary biology. His hypothesis on natural selection, created along with Alfred Wallace, is accepted as the most important mechanism of evolution.2 A similar situation occurs with diabetes.
This paper critically examines Florence Nightingale's legacy and its ongoing relevance to contemporary patient safety. Drawing on Notes on Nursing, the study highlights Nightingale's emphasis on hygiene, cleanliness, environmental factors, and systematic care as foundational to reducing harm and improving patient outcomes. Her insights laid the groundwork for infection prevention and control practices that remain central to modern nursing and healthcare safety protocols. Nightingale's principles align closely with current patient safety frameworks and global initiatives, such as the World Health Organization's Global Action Plan, emphasizing the social responsibility of healthcare professionals. Despite scientific advances and evolving healthcare systems, her legacy continues to influence nursing practices by reinforcing systematized, ethical, and patient-centered care. This enduring relevance underscores the critical role of nursing in safeguarding health and promoting safety in diverse clinical settings. This study advocates for ongoing recognition and integration of Nightingale's principles to enhance patient safety and care quality in modern healthcare. Her legacy remains an epistemological and practical resource for advancing nursing theory, patient-centered care, and critical reflection in healthcare. Trial Registration: Not applicable.
The heritability of fertility behavior altered during the profound societal changes that occurred from the 1950s onward in Norway. Societal changes modify the heritability of age at first birth and number of children, and the change in heritability varies by gender and outcome. A theoretical explanation that suggests norms weakened and opportunities broadened across the latter part of the twentieth century and into the early twenty-first century, thereby increasing heritability, falls short. Results provide some support for the hypothesis that the importance of genes increases during periods of societal change, when linked to the transition to dualearner families and family policy implementation. The study highlights the importance of considering societal structures and gender differences when investigating genetic influences on fertility behavior.
In this review, we emphasize on ternary deep eutectic solvents (TDESs) utilized in environmental and analytical chemistry for separation and sensing purposes in contrast to their binary counterparts, known as simple deep eutectic solvents (DESs). To ensure food security, high water quality, and environmental protection from the current industrialized era of the twenty-first century, it is of utmost importance to determine and separate effluents, pollutants, or any undesired materials in our related day-to-day utilities, foods, or nature using a more efficient and green separating media or sensor. For this reason, there is no better choice for an analytical chemist to design and use hybrid and natural ternary deep eutectic solvents, with enhanced physicochemical properties. Since the discovery of simple binary DESs, they have been applied in sensing and separation sciences, but the invention of ternary deep eutectic solvents has made them a more interesting and suitable candidate for the development of separation or sensor methodologies based on TDESs. Furthermore, we explore TDES structure-property relationships, showing how the choice of components dictates macroscopic properties. This molecular-level understanding facilitates the rational design of tailored solvents for analytical applications. This review consolidates recent advances in TDES-based sensing and separation to support future research.
This paper examines how the seventeenth-century Dutch Cartesian Johannes de Raey sought to reconcile the philosophies of Descartes and Aristotle. It focuses on De Raey's identification in Aristotle of a doctrine corresponding to Descartes's subtle matter and asks which strand of the Aristotelian tradition he relied on for this identification. The study centres on De Raey's 1652 disputation De materia subtili and also draws on his lecture notes preserved in manuscript form, his earliest disputation, and the disputations of his teacher Henricus Regius, in which De Raey often served as respondent. The analysis shows, first, that De Raey interpreted Aristotle as positing a subtle body analogous to the element of the stars. Second, it argues that De Raey arrived at this reading by relying on the interpretation of the Generation of Animals by the Wittenberg medical professor Daniel Sennert, whose works De Raey encountered early in his career while studying medicine under Regius. Finally, De Raey gave Sennert's interpretation a decisively materialist turn, thereby making it possible to read Aristotle within a corpuscular, Cartesian framework. In this respect, he can be placed within the broader seventeenth-century movement to reinterpret Sennert's Aristotelianism in corpuscular terms.
Este ensayo reflexiona sobre el significado de la condecoración Eduardo Liceaga a partir de la tradición higienista y de salud pública en México. A través de la figura de Liceaga se revisan paralelos históricos en la construcción de instituciones, la formación de recursos humanos y la defensa de políticas basadas en evidencia frente a riesgos sanitarios clásicos y emergentes, como la contaminación atmosférica y la exposición al plomo. El texto subraya la dimensión colectiva de la salud pública, anclada en la vocación de servicio de maestros, colegas, servidores públicos y nuevas generaciones. Finalmente, propone la equidad y la esperanza como ejes para afrontar la insuficiente inversión preventiva y la actual vorágine institucional, manteniendo "el espíritu ascendente de la salud pública" como horizonte ético y profesional.