Medical schools in empires: connecting the dots.

This article provides an overview of the historiography of medical education and calls for greater attention to the connections between medical schools. It begins by reviewing research on medical education in imperial metropoles. Researchers have compared medical schools in different national contexts, traced travellers between them or examined the hierarchies that medical education created within the medical profession. The article then shows how historians have emphasised the ways in which medicine in colonial empires was shaped by negotiation, exchange, hybridisation and competition. The final part of the article introduces the special issue 'Medical Education in Empires'. Drawing on a variety of sources in English, French, Dutch and Chinese, the special issue builds on these historiographies by juxtaposing cases of medical schools in imperial contexts since the eighteenth century. It considers who funded these medical schools and why, what models of medicine underpinned their creation, what social changes they contributed to, what life was like in these schools, who the students and teachers were and what graduates did with their medical careers. This special issue thus contributes to clarifying the role of medical education in empires and the long-term impact of empires on the medical world.

Crafting British medicine in the Empire: the establishment of medical schools in India and Canada, 1763-1837.

In the early nineteenth century, medical schools became a growing means of regulating medicine in the British Empire, both in the metropole and in two colonies: India and Canada. By examining the establishment of medical schools in Calcutta, Bombay, Madras, Quebec City, Montreal and Toronto between the end of the Seven Years' War and the beginning of the Victorian era, this article argues that the rise of the British Empire was a key factor in the gradual replacement of private medical apprenticeships with institutional medical education. Although the imperial state did not implement a uniform medical policy across the British Empire, the medical schools established under its jurisdiction were instrumental in devising a curriculum that emphasised human dissection, bedside training in hospitals and organic chemistry as criteria of medical competence.

Evaluation of integrated disease surveillance and response (IDSR) and early warning and response network (EWARN) in South Sudan 2021.

Introduction: South Sudan has been implementing the Integrated Disease Surveillance and Response (IDSR) strategy since 2006, along with Early Warning and Alert Response and Network (EWARN). The IDSR/EWARN stakeholders commissioned an independent evaluation to establish performance at national, state, county, health facility, and community levels in the first half of 2021. Methods: the evaluation was conducted between June and September 2021 (during the COVID-19 pandemic) and was based on the World Health Organization (WHO) protocols for monitoring and evaluating communicable disease surveillance and response systems and the guidelines for evaluating EWARN. Results: integrated disease surveillance and response/early warning and alert response and network indicator data showed improving timeliness and completeness from the beginning of 2021 to week 16 and then a slight depression of timeliness by week 32, while completeness remained high. Event-based surveillance was active at the beginning of 2021 and in week 32. However, there was inadequate sample collection to investigate acute watery diarrhea, bloody diarrhea, and acute jaundice syndrome alerts. Respondents in all cadres had substantial experience working in IDSR/EWARN. All respondents performed the various IDSR/EWARN tasks and duties as expected, but needed more resources and training. Conclusion: while IDSR/EWARN is performing relatively well, confirmation of priority diseases by the laboratories needs to be strengthened. Health facilities need more regular supervision from the higher levels. Community health workers need more training on IDSR/EWARN. The whole IDSR/EWARN system needs more resources, particularly for communication and transport and to confirm priority diseases. Staff at all levels requested more training in IDSR/EWARN.

Integrated disease surveillance and response in humanitarian context: South Sudan experience.

Introduction: decades of instability continue to impact the implementation of the Integrated Disease Surveillance and Response (IDSR) strategy. The study reviewed the progress and outcomes of rolling out IDSR in South Sudan. Methods: this descriptive cross-sectional study used epidemiological data for 2019, 2020, and other program data to assess indicators for the five surveillance components including surveillance priorities, core and support functions, and surveillance system structure and quality. Results: South Sudan expanded the priority disease scope from 26 to 59 to align with national and regional epidemiological trends and the International Health Regulations (IHR) 2005. Completing the countrywide rollout of electronic Early Warning Alert and Response (EWARS) reporting has improved both the timeliness and completeness of weekly reporting to 78% and 90%, respectively, by week 39 of 2020 in comparison to a baseline of 54% on both timeliness and completeness of reporting in 2019. The National Public Health Laboratory confirmatory testing capacities have been expanded to include cholera, measles, HIV, tuberculosis (TB), influenza, Ebola, yellow fever, and Severe Acute Respiratory Syndrome 2 (SARS-COV-2). Rapid response teams have been established to respond to epidemics and pandemics. Conclusion: since 2006, South Sudan has registered progress towards using indicator and event-based surveillance and continues to strengthen IHR (2005) capacities. Following the adoption of third edition IDSR guidelines, the current emphasis entails maintaining earlier gains and strengthening community and event-based surveillance, formalizing cross-sectoral one-health engagement, optimal EWARS and District Health Information Systems (DHIS2) use, and strengthening cross-border surveillance. It is also critical that optimal government, and donors' resources are dedicated to supporting health system strengthening and disease surveillance.

Voyager pour apprendre : les Canadiens reçus docteurs en médecine à Paris au XIXe siècle.

Thirteen Canadians obtained a doctoral degree from the Faculty of Medicine of Paris between 1822 and 1905. Their studies in France played a decisive role in some of the major trends of 19th-century Canadian history: the formation of a French-Canadian professional bourgeoisie, the formalization of diplomatic ties between Canada and France, the development of bacteriology in America, and the rise of French-Canadian nationalism at the turn of the 20th century. This article traces the careers of these medical doctors by using unpublished sources, mainly their student files and doctoral theses, located through the Pierre Moulinier database and made available by the Bibliothèque Interuniversitaire de Santé of the Université Paris-Descartes. By examining these doctors' travels to Paris, it shows the impact on the Canadian medical profession of the relationship between a former North American colony and its former imperial capital.

Treize Canadiens sont reçus docteurs à la Faculté de médecine de Paris entre 1822 et 1905. Leurs séjours en France jouent un rôle déterminant dans certaines tendances majeures de l'histoire canadienne du XIXe siècle, notamment la formation d'une bourgeoisie professionnelle canadienne-française, l'officialisation des liens diplomatiques entre le Canada et la France, l'essor de la bactériologie en Amérique et la montée du nationalisme canadien-français au tournant du XXe siècle. Grâce à des sources inédites, principalement les dossiers étudiants et les thèses doctorales recueillis dans le fichier Pierre Moulinier de la Bibliothèque Interuniversitaire de Santé de l'Université Paris-Descartes, cet article retrace les parcours de ces docteurs canadiens. En s'attardant à leurs séjours à Paris, il examine les effets sur la profession médicale des rapports entre une ancienne colonie d'Amérique du Nord et sa première capitale impériale.

Update on the mesentery: structure, function, and role in disease.

Over the past 5 years, systematic investigation of the mesenteric organ has expanded and shown that the mesentery is the organ in and on which all abdominal digestive organs develop and remain connected to. In turn, this observation has clarified the anatomical foundation of the abdomen and the fundamental order at that level. Findings related to the shape and development of the mesentery have illuminated its function, advancing our understanding of the pathobiology, diagnosis, and treatment of several abdominal and systemic diseases. Inclusion of the mesentery in surgical resections alters the course of benign and malignant diseases. Mesenteric-based scoring systems can enhance the radiological interpretation of abdominal disease. Emerging findings reconcile observations across scientific and clinical fields and have been assimilated into reference curricula and practice guidelines. This Review summarises the developmental, anatomical, and clinical advances made since the mesentery was redesignated as an organ in 2016.

Voyager pour apprendre : les Canadiens reçus docteurs en médecine à Paris au XIXe siècle.

Thirteen Canadians obtained a doctoral degree from the Faculty of Medicine of Paris between 1822 and 1905. Their studies in France played a decisive role in some of the major trends of 19th-century Canadian history: the formation of a French-Canadian professional bourgeoisie, the formalization of diplomatic ties between Canada and France, the development of bacteriology in America, and the rise of French-Canadian nationalism at the turn of the 20th century. This article traces the careers of these medical doctors by using unpublished sources, mainly their student files and doctoral theses, located through the Pierre Moulinier database and made available by the Bibliothèque Interuniversitaire de Santé of the Université Paris-Descartes. By examining these doctors' travels to Paris, it shows the impact on the Canadian medical profession of the relationship between a former North American colony and its former imperial capital.

Treize Canadiens sont reçus docteurs à la Faculté de médecine de Paris entre 1822 et 1905. Leurs séjours en France jouent un rôle déterminant dans certaines tendances majeures de l'histoire canadienne du XIXe siècle, notamment la formation d'une bourgeoisie professionnelle canadienne-française, l'officialisation des liens diplomatiques entre le Canada et la France, l'essor de la bactériologie en Amérique et la montée du nationalisme canadien-français au tournant du XXe siècle. Grâce à des sources inédites, principalement les dossiers étudiants et les thèses doctorales recueillis dans le fichier Pierre Moulinier de la Bibliothèque Interuniversitaire de Santé de l'Université Paris-Descartes, cet article retrace les parcours de ces docteurs canadiens. En s'attardant à leurs séjours à Paris, il examine les effets sur la profession médicale des rapports entre une ancienne colonie d'Amérique du Nord et sa première capitale impériale.

Combination of Dark-Field and Confocal Microscopy for the Optical Detection of Silver and Titanium Nanoparticles in Mammalian Cells.

We describe here two optical microscopy techniques-dark-field confocal light scanning microscopy (DF-CLSM) and dark-field wide-field confocal microscopy (DF-WFCM), that can be used to study interaction between nanoparticles and cells in 3D space. Dark field microscopy can detect very small structures below the diffraction limit of conventional light microscopes, while a confocal setup provides vertical sectioning capabilities to render specimens in 3D. The use of DF-WFCM instead of DF-CLSM allows faster sample processing but yields lower resolution. We used a retinal pigment epithelial cell line ARPE-19 to illustrate different optical and lighting conditions necessary for optimal imaging of metal and metal oxide nanoparticles (TiO2 and Ag). Our experimental setup primarily involved an E-800 Nikon and Nikon Ni upright microscopes and a Nikon Ti2 microscope connected to a xenon light source along with special dark-field objectives. For confocal studies we used either Leica and Nikon inverted confocal microscopes. For microscopic analyses, ARPE-19 cells were fixed in situ in cultured chamber slides or collected from T-25 flasks and then fixed in suspension. At the lowest concentrations of TiO2 or Ag tested (0.1-0.3 µg/mL), we were able to detect as few as 5-10 nanoparticles per cell due to intense light scattering by the particles. The degree of brightness detected indicated that the uptake of nanoparticles within ARPE-19 cells could be monitored using dark-field microscopy. Here we describe how to use wide-field microscopy to follow nanoparticle uptake by cells and how to assess some aspects of cellular health in in vitro cell cultures exposed to nanoparticles.

Detection of Silver and TiO2 Nanoparticles in Cells by Flow Cytometry.

Evaluation of the potential hazard of man-made nanomaterials has been hampered by a limited ability to observe and measure nanoparticles in cells. A FACSCalibur™ flow cytometer and a Stratedigm S-1000 flow cytometer were used to measure changes in light scatter from cells after incubation with either silver nanoparticles (AgNP) or TiO2 nanoparticles. Within the range of between 0.1 µg/mL and 30 µg/mL the nanoparticles caused a proportional increase of the side scatter and decrease of the forward scatter intensity signals. At the lowest concentrations of TiO2 (ranging between 0.1 µg/mL and 0.3 µg/mL), the flow cytometer can detect as few as 5-10 nanoparticles per cell. The influence of nanoparticles on the cell cycle was detected by nonionic detergent lysis of nanoparticle incubated cells that were stained with DAPI or propidium iodide (PI). Viability of nanoparticle treated cells was determined by PI exclusion. Surface plasmonic resonance (SPR) was detected primarily in the far-red fluorescence detection channels after excitation with a 488 nm laser.Our results suggest that the uptake of nanoparticles within cells can be monitored using flow cytometry. This uptake of nanoparticle data was confirmed by viewing the nanoparticles in the cells using dark-field microscopy. The flow cytometry detection of nanoparticles approach may help fill a critical need to assess the relationship between nanoparticle dose and cellular toxicity. Such experiments using nanoparticles could potentially be performed quickly and easily using the flow cytometer to measure both nanoparticle uptake and cellular health.

Cognitive correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia.

Patients with childhood onset schizophrenia (COS) display widespread gray matter (GM) structural brain abnormalities. Healthy siblings of COS patients share some of these structural abnormalities, suggesting that GM abnormalities are endophenotypes for schizophrenia. Another possible endophenotype for schizophrenia that has been relatively unexplored is corticostriatal dysfunction. The corticostriatal system plays an important role in skill learning. Our previous studies have demonstrated corticostriatal dysfunction in COS siblings with a profound skill learning deficit and abnormal pattern of brain activation during skill learning. This study investigated whether structural abnormalities measured using volumetric brain morphometry (VBM) were present in siblings of COS patients and whether these were related to deficits in cognitive skill learning. Results revealed smaller GM volume in COS siblings relative to controls in a number of regions, including occipital, parietal, and subcortical regions including the striatum, and greater GM volume relative to controls in several subcortical regions. Volume in the right superior frontal gyrus and cerebellum were related to performance differences between groups on the weather prediction task, a measure of cognitive skill learning. Our results support the idea that corticostriatal and cerebellar impairment in unaffected siblings of COS patients are behaviorally relevant and may reflect genetic risk for schizophrenia.

Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol.

Comparative whole-genome sequencing enables the identification of specific mutations during adaptation of bacteria to new environments and allelic replacement can establish their causality. However, the mechanisms of action are hard to decipher and little has been achieved for epistatic mutations, especially at the metabolic level. Here we show that a strain of Escherichia coli carrying mutations in the rpoC and glpK genes, derived from adaptation in glycerol, uses two distinct metabolic strategies to gain growth advantage. A 27-bp deletion in the rpoC gene first increases metabolic efficiency. Then, a point mutation in the glpK gene promotes growth by improving glycerol utilization but results in increased carbon wasting as overflow metabolism. In a strain carrying both mutations, these contrasting carbon/energy saving and wasting mechanisms work together to give an 89% increase in growth rate. This study provides insight into metabolic reprogramming during adaptive laboratory evolution for fast cellular growth.

Impaired automatization of a cognitive skill in first-degree relatives of patients with schizophrenia.

We studied healthy, first-degree relatives of patients with schizophrenia to test the hypothesis that deficits in cognitive skill learning are associated with genetic liability to schizophrenia. Using the Weather Prediction Task (WPT), 23 healthy controls and 10 adult first-degree Relatives Of Schizophrenia (ROS) patients were examined to determine the extent to which cognitive skill learning was automated using a dual-task paradigm to detect subtle impairments in skill learning. Automatization of a skill is the ability to execute a task without the demand for executive control and effortful behavior and is a skill in which schizophrenia patients possess a deficit. ROS patients did not differ from healthy controls in accuracy or reaction time on the WPT either during early or late training on the single-task trials. In contrast, the healthy control and ROS groups were differentially affected during the dual-task trials. Our results demonstrate that the ROS group did not automate the task as well as controls and continued to rely on controlled processing even after extensive practice. This suggests that adult ROS patients may engage in compensatory strategies to achieve normal levels of performance and support the hypothesis that impaired cognitive skill learning is associated with genetic risk for schizophrenia.

Evidence for corticostriatal dysfunction during cognitive skill learning in adolescent siblings of patients with childhood-onset schizophrenia.

Patients with schizophrenia perform poorly on cognitive skill learning tasks. This study is the first to investigate the neural basis of impairment in cognitive skill learning in first-degree adolescent relatives of patients with schizophrenia. We used functional magnetic resonance imaging to compare activation in 16 adolescent siblings of patients with childhood-onset schizophrenia (COS) and 45 adolescent controls to determine whether impaired cognitive skill learning in individuals with genetic risk for schizophrenia was associated with specific patterns of neural activation. The siblings of patients with COS were severely impaired on the Weather Prediction Task (WPT) and showed a relative deactivation in frontal regions and in the striatum after extensive training on the WPT compared with controls. These differences were not accounted for by performance differences in the 2 groups. The results suggest that corticostriatal dysfunction may be part of the liability for schizophrenia.

The influence of lithium on calcium homeostasis in older patients in daily clinical practice.

BACKGROUND: Lithium can influence calcium homeostasis resulting in changes in parathormone set point and renal calcium handling. The clinical significance of these changes in older patients is unknown. The objective of this study was to investigate the possible association between duration of lithium treatment and corrected calcium, parathormone and 24-h urinary calcium excretion in older psychiatric patients corrected for renal function and vitamin 25OH D and also to estimate the point prevalence of hypercalcemia and raised parathormone. METHODS: A cross-sectional study of psychiatric outpatients visiting a specialized facility for older patients treated with lithium was performed. Patients underwent a comprehensive assessment and blood and urine testing. Potential confounders of calcium homeostasis were recorded. On the basis of the duration of lithium treatment, patients were divided into four groups. RESULTS: One hundred eleven patients were included, mean age 75.2 years. There was no significant association between the duration of lithium treatment and corrected calcium, parathormone and 24-h urinary calcium excretion. The point prevalence of hypercalcemia was 2.7% and 47.8% for raised parathormone. There was an unexpected but significant negative association between the duration of lithium treatment and vitamin 25OH D, with 76.9% vitamin 25OH D deficiency (<50 nmol/L) in the group using lithium for more than 10 years. CONCLUSIONS: No association was found between duration of lithium treatment and calcium parameters in older psychiatric outpatients, but there was a high prevalence of raised parathormone and an unexpected negative association between duration of lithium treatment and 25OH D.

Cholesterol sulfate and cholesterol sulfotransferase inhibit gluconeogenesis by targeting hepatocyte nuclear factor 4α.

Sulfotransferase (SULT)-mediated sulfation represents a critical mechanism in regulating the chemical and functional homeostasis of endogenous and exogenous molecules. The cholesterol sulfotransferase SULT2B1b catalyzes the sulfoconjugation of cholesterol to synthesize cholesterol sulfate (CS). In this study, we showed that the expression of SULT2B1b in the liver was induced in obese mice and during the transition from the fasted to the fed state, suggesting that the regulation of SULT2B1b is physiologically relevant. CS and SULT2B1b inhibited gluconeogenesis by targeting the gluconeogenic factor hepatocyte nuclear factor 4α (HNF4α) in both cell cultures and transgenic mice. Treatment of mice with CS or transgenic overexpression of the CS-generating enzyme SULT2B1b in the liver inhibited hepatic gluconeogenesis and alleviated metabolic abnormalities both in mice with diet-induced obesity (DIO) and in leptin-deficient (ob/ob) mice. Mechanistically, CS and SULT2B1b inhibited gluconeogenesis by suppressing the expression of acetyl coenzyme A (acetyl-CoA) synthetase (Acss), leading to decreased acetylation and nuclear exclusion of HNF4α. Our results also suggested that leptin is a potential effector of SULT2B1b in improving metabolic function. We conclude that SULT2B1b and its enzymatic by-product CS are important metabolic regulators that control glucose metabolism, suggesting CS as a potential therapeutic agent and SULT2B1b as a potential therapeutic target for metabolic disorders.

PXR ablation alleviates diet-induced and genetic obesity and insulin resistance in mice.

The pregnane X receptor (PXR), along with its sister receptor constitutive androstane receptor (CAR), was initially characterized as a xenobiotic receptor that regulates drug metabolism. In this study, we have uncovered an unexpected endobiotic role of PXR in obesity and type 2 diabetes. PXR ablation inhibited high-fat diet (HFD)-induced obesity, hepatic steatosis, and insulin resistance, which were accounted for by increased oxygen consumption, increased mitochondrial ß-oxidation, inhibition of hepatic lipogenesis and inflammation, and sensitization of insulin signaling. In an independent model, introducing the PXR(-/-) allele into the ob/ob background also improved body composition and relieved the diabetic phenotype. The ob/ob mice deficient of PXR showed increased oxygen consumption and energy expenditure, as well as inhibition of gluconeogenesis and increased rate of glucose disposal during euglycemic clamp. Mechanistically, the metabolic benefits of PXR ablation were associated with the inhibition of c-Jun NH2-terminal kinase activation and downregulation of lipin-1, a novel PXR target gene. The metabolic benefit of PXR ablation was opposite to the reported prodiabetic effect of CAR ablation. Our results may help to establish PXR as a novel therapeutic target, and PXR antagonists may be used for the prevention and treatment of obesity and type 2 diabetes.

Detection of TiO2 nanoparticles in cells by flow cytometry.

Evaluation of the potential hazard of man-made nanomaterials has been hampered by a limited ability to observe and measure nanoparticles in cells. A FACSCalibur™ flow cytometer was used to measure changes in light scatter from cells after incubation with TiO(2) nanoparticle. Both the side scatter and forward scatter changed substantially in response to the TiO(2). Between 0.1 and 30 µg/mL TiO(2), the side scatter increased sequentially while the forward scatter decreased, presumably due to substantial light reflection by the TiO(2) particles. At the lowest concentrations of TiO(2) (0.1-0.3 µg/mL), the flow cytometer apparently could detect as few as 5-10 nanoparticles per cell as shown using dark field microscopy. The influence of nanoparticles on the cell cycle was detected by nonionic detergent lysis of nanoparticle-incubated cells. Viability of nanoparticle-treated cells was determined by PI exclusion.These data suggest that the uptake of nanoparticles within cells can be monitored using flow cytometry and confirmed by dark field microscopy. This approach may help fill a critical need to assess the relationship between nanoparticle dose and cellular toxicity. Such experiments could potentially be performed quickly and easily using the flow cytometer to measure both nanoparticle uptake and cellular health.

Microscopy imaging methods for the detection of silver and titanium nanoparticles within cells.

Scientific evaluation of potential environmental hazards resulting from man-made nanomaterials has been hampered by the inability to optimally detect cell-associated nanoparticles. We have successfully imaged TiO(2) nanoparticles in ARPE-19 cells using different light microscope modalities commonly available to investigators including fluorescence, dark field, phase, interference, and confocal. In this report, we describe different optical and lighting conditions necessary for optimal nanoparticle imaging in ARPE-19 cells.Microscopic examinations involved an E-800 Nikon microscope connected to a xenon light source along with special dark field objectives. For microscopy analyses, ARPE-19 cells were fixed in situ in cultured chamber slides or collected from T-25 flasks and then fixed in suspension. At the lowest concentrations of TiO(2) (0.1-0.3 µg/mL), it was possible to detect as few as 5-10 nanoparticles per cell due to intense light scattering by TiO(2). The degree of brightness detected indicated that the uptake of nanoparticles within ARPE-19 cells could be monitored using dark field microscopy. This report details how wide-field microscopy can be effectively used to detect nanoparticle uptake as well as to assess cellular health in ARPE-19 cell cultures.