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TABLE DES MATIERES I. Introduction II. Contexte et besoin d'accompagnement lors de l'entrevue sur les faits III. Les accompagnateurs et accompagnatrices, des temoins contraignables? A. Les declarations anterieures incompatibles: une [...], CET ARTICLE SE penche sur la question de l'accompagnement des personnes victimes lorsqu'elles sont appelees a participer a une entrevue portant sur les faits relies a leurs plaintes avec des membres de la police. L'article critique le recours a l'entretien sur les faits sans option d'accompagnement de la personne victime. Pour ce faire, il commence par etablir la necessite de l'accompagnement en offrant une mise en contexte portant principalement sur l'accompagnement des personnes victimes d'agressions sexuelles et de crimes policiers. Ensuite, la recherche aborde divers enjeux invoques a l'encontre de l'accompagnement, incluant les regles de preuve quant aux declarations anterieures incompatibles, le droit a une defense pleine et entiere et l'impact de l'enregistrement video sur la personne victime. A cette occasion, l'article offre diverses solutions pour reconcilier l'accompagnement des personnes victimes et les droits de la personne accusee dans le contexte d'agressions sexuelles. Pour se faire, l'auteure s'appuie principalement sur la jurisprudence de la Cour supreme du Canada, les articles 276 et 278.92 du Code criminel et l'etat des connaissances scientifiques portant sur les declarations incompatibles, le contact entre la police et les personnes victimes d'agressions sexuelles ainsi que sur les effets d'un traumatisme sur la memoire. Enfin, l'article se termine par une discussion faisant etat de certains autres obstacles tels que les modalites d'accompagnement et l'influence d'une tierce partie sur la personne victime. Cette discussion, ainsi que l'ensemble de l'article, rappellent l'importance de favoriser l'autonomie et la dignite des personnes victimes dans toutes decisions concernant leur participation au processus de judiciarisation des plaintes. THIS ARTICLE EXPLORES the issue of providing support for victims when they are called upon to be interviewed by members of the police force on matters relating to their allegations. The article criticizes the use of fact-finding interviews without providing the option of support to the victim. It begins by establishing the need for support by presenting it mainly within the context of support for victims of sexual assault and police crimes. The research then addresses various issues raised against providing support, including the rules of evidence regarding prior inconsistent statements, the right to full answer and defence, and the impact of video recording on the victim. In that vein, the article offers various solutions reconciling the support of victims and the rights of the accused in the context of sexual assault. To do so, the author draws mainly on Supreme Court of Canada case law, sections 276 and 278.92 of the Criminal Code, and the state of scientific knowledge regarding inconsistent statements, contact between police and people who were victims of sexual assault, and the effects of trauma on memory. Finally, the article concludes with a discussion on other obstacles, such as the rules of support and the influence of a third party on the victim. This discussion, along with this whole article, serves as a reminder of the importance of fostering the autonomy and dignity of victims in all decisions concerning their participation in the judicial complaints process.

Oncocytic follicular cell-derived thyroid neoplasms, formerly known as Hurthle cell tumors, are characterized by expansile nodular growths of thyroid follicular epithelium displaying abundant granular eosinophilic cytoplasm. The topic of oncocytic [...], * Context.--Oncocytic thyroid tumors displaying a papillary growth pattern are rare and may cause diagnostic problems. Objective.--To examine the clinicopathologic features of a series of 32 follicular cell-derived tumors composed of cells with oncocytic cytoplasm and displaying papillary architecture. Design.--Thirty-two cases were collected and studied to assess clinicopathologic features, including immunohistochemical and molecular testing for BRAF V600E. Results.--The patients were 26 women and 6 men, aged 17 to 77 years. The nodules ranged from 0.3 to 6.0 cm. Eighteen cases showed features of oncocytic hyperplastic nodules and were identified against a background of thyroid follicular nodular disease; 4 cases showed features of oncocytic follicular adenoma; and 10 cases corresponded to carcinomas with oncocytic and papillary features. Nuclear features of papillary thyroid carcinoma were absent or exceedingly rare. All cases were negative for HBME-1 and cytokeratin 19 (CK19) and wild type for BRAF V600E. Follow-up in 25 patients showed that all patients with hyperplastic nodules and oncocytic follicular adenomas were alive and well and free of disease from 7 to 20 years. One patient with oncocytic follicular carcinoma showed metastases and died of tumor at 16 months; 2 patients with carcinoma had metastases and recurrence at 6 and 7 years; and 5 patients with invasive tumors were free of disease from 5 to 10 years. Conclusions.--Oncocytic thyroid tumors with papillary features can span a spectrum from benign hyperplastic, to encapsulated neoplastic, to invasive malignant lesions. Owing to their papillary features, it is important not to confuse them for other types of thyroid tumors, such as oncocytic papillary thyroid carcinoma. (Arch Pathol Lab Med. 2024;148:997-1006; doi: 10.5858/arpa.2023-0309-OA)

Understanding of the biology, pathology, and natural history of cystic lesions of the pancreas has expanded dramatically. As recently as the 1970s, all tumors of the pancreas with cystic morphology [...], * Context.--Macroscopic precursor lesions of the pancreas represent a complex clinical management problem. Molecular characterization of pancreatic cysts has helped to confirm and refine clinical and pathologic classifications of these lesions, inform our understanding of tumorigenesis in the pancreas, and provide opportunities for preoperative diagnosis. Objective.--To review the pathologic classification of macroscopic cystic lesions of the pancreas: intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), intraductal oncocytic papillary neoplasms (IOPNs), and intraductal tubulopapillary neoplasms (ITPNs), and to describe our current state of understanding of their molecular underpinnings, relationship to invasive carcinomas, and implications for diagnosis and prognostication. Data Sources.--We assessed the current primary literature and current World Health Organization Classification of Digestive System Tumours. Conclusions.--Macroscopic cystic lesions of the pancreas are morphologically and molecularly diverse. IPMNs and MCNs share mucinous cytoplasm with papillae. MCNs are defined by ovarian-type stroma. IOPNs have granular eosinophilic cytoplasm, prominent nucleoli, and complex, arborizing papillae. ITPNs demonstrate complex, back-to-back tubules and anastomosing papillae and lack prominent intracellular mucin. IPMNs and MCNs are characterized by driver mutations in KRAS/ GNAS (IPMNs) and KRAS (MCNs), with later driver events in RNF43, CDKN2A, SMAD4, and TP53. In contrast, IOPNs and ITPNs have recurrent rearrangements in PRKACA/PRKACB and MAPK-associated genes, respectively. The recurrent alterations described in cysts provide an opportunity for diagnosis using aspirated cyst fluid. Molecular characterization of IPMNs shows a striking spatial and mutational heterogeneity, challenging traditional models of neoplastic development and creating challenges to interpretation of cyst fluid sequencing results. (Arch Pathol Lab Med. 2024;148:980-988; doi: 10.5858/arpa.2023-0358-RA)

Pancreatic neuroendocrine neoplasms (PanNENs) represent a heterogeneous group of epithelial tumors of the pancreas showing a neuroendocrine differentiation. (1-4) Among all pancreatic malignancies, the prevalence of PanNENs is around 2% [...], * Context.--Pancreatic neuroendocrine neoplasms (PanNENs) represent a heterogeneous group of epithelial tumors of the pancreas showing neuroendocrine differentiation. These neoplasms are classified into well-differentiated pancreatic neuroendocrine tumors (PanNETs), which include G1, G2, and G3 tumors, and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs), which are G3 by definition. This classification mirrors clinical, histologic, and behavioral differences and is also supported by robust molecular evidence. Objective.--To summarize and discuss the state of the art regarding neoplastic progression of PanNENs. A better comprehension of the mechanisms underpinning neoplastic evolution and progression of these neoplasms may open new horizons for expanding biologic knowledge and ultimately for addressing new therapeutic strategies for patients with PanNENs. Data Sources.--Literature review of published studies and the authors' own work. Conclusions.--PanNETs can be seen as a unique category, where G1-G2 tumors may progress to G3 tumors mainly driven by DAXX/ATRX mutations and alternative lengthening of telomeres. Conversely, PanNECs display totally different histomolecular features more closely related to pancreatic ductal adenocarcinoma, including TP53 and Rb alterations. They seem to derive from a nonneuroendocrine cell of origin. Even the study of PanNEN precursor lesions corroborates the rationale of considering PanNETs and PanNECs as separate and distinct entities. Improving the knowledge regarding this dichotomous distinction, which guides tumor evolution and progression, will represent a critical basis for PanNEN precision oncology. (Arch Pathol Lab Med. 2024;148:975-979; doi: 10.5858/arpa.2022-0417-RA)

Intraductal papillary neoplasm of the bile duct (IPNB) is a precursor lesion of cholangiocarcinoma. (1-3) Since the concept of this neoplasm was proposed almost 20 years ago, (4) it has [...], * Context.--Intraductal papillary neoplasm of the bile duct (IPNB) is classified into types 1 and 2 based on criteria proposed in 2019. Recent studies investigated the clinicopathologic and molecular features of IPNB, which contributed to a more detailed understanding of this undercharacterized neoplasm. Objective.--To summarize driver gene mutations, radiologic tumor evolution, and a potentially unique pattern of tumor progression in IPNB. Data Sources.--Data were derived from a literature review and personal clinical and research experiences. Conclusions.--In contrast to de novo cholangiocarcinoma, type 1 IPNB often has mutations in APC, CTNNB1, STK11, and GNAS. These molecular features are shared with intraductal papillary mucinous neoplasm of the pancreas; however, the frequencies of individual gene abnormalities differ between these 2 neoplasms. A radiologic review of sequential images suggested that type 1 IPNB is a slow-growing neoplasm, with an ~1-cm increase in size every 2 to 3 years, and remains in a noninvasive state for many years. A similar papillary neoplasm may develop in the biliary tree years after the complete surgical resection of IPNB. The second neoplasm has the same genetic abnormalities as the first neoplasm, indicating intrabiliary implantation rather than multifocal lesions. In contrast to type 1 IPNB, most cases of type 2 IPNB have invasive malignancy at the initial presentation. Type 2 IPNB shares many clinicopathologic and molecular features with de novo cholangiocarcinoma, questioning the distinctness of this tumor entity. The molecular mechanisms underlying malignant transformation in IPNB warrant further study. (Arch Pathol Lab Med. 2024;148:989-996; doi: 10.5858/arpa.2022-0407-RA)

We report a case of Taenia solium taeniasis in a 10-year-old child in Timor-Leste, confirmed by molecular analysis, suggesting T. solium transmission to humans is occurring in Timor-Leste. Proactive measures [...]

Background: The aim of our work was to examine differences between trauma patients in rural and urban areas who presented to a tertiary trauma centre in the province of Saskatchewan, Canada. Methods: We identified a historical cohort of all level 1 trauma activations presenting to Royal University Hospital (RUH) from April 1, 2020, to March 31, 2022. We divided the cohort into 2 groups (urban and rural), according to the trauma location. The primary outcome of interest was 30-day mortality. Secondary outcomes of interest were hospital length of stay, readmission to hospital within 30 days of discharge, and complication rate. Results: Trauma patients in rural areas were younger (34.1 v. 37 yr; p = 0.002) and more likely to be male (80.3% v. 74.4%; p = 0.040), with higher Injury Severity Scores (12.3 v. 8.3; p < 0.0001). Trauma patients in urban areas were more likely to sustain penetrating trauma (42.5% v. 28.5%; p < 0.0001). We saw no differences in morbidity and mortality between the 2 groups, but the rural trauma group had longer median lengths of stay (5 v. 3 d; p < 0.0007). Conclusion: Although we identified key differences in patient demographics, injury type, and injury severity, outcomes were largely similar between the urban and rural trauma groups. This finding contradicts comparable studies within Canada and the United States, a difference that may be attributable to the lack of inclusion of prehospital mortality in the rural trauma group. The longer length of stay in trauma patients from rural areas may be attributed to disposition challenges for patients who live remotely. Contexte: Notre travail avait pour but d'analyser les diff rences entre les patient les de traumatologie provenant de milieux ruraux et urbains ayant consult dans un centre de traumatologie tertiaire de la province de la Saskatchewan, au Canada. M thodes: Nous avons constitu une cohorte historique de tous les cas d'activation de niveau 1 en traumatologie ayant consult l'H pital universitaire royal entre le 1er avril 2020 et le 31 mars 2022. Nous avons scind la cohorte en 2 groupes (milieux urbains et ruraux), selon le lieu de survenue du traumatisme. Le param tre principal tait la mortalit 30 jours. Les param tres secondaires taient la dur e du s jour hospitalier, la r hospitalisation dans les 30 jours suivant le cong , et le taux de complications. R sultats: La patient le de traumatologie provenant de r gions rurales tait plus jeune (34,1 c. 37 ans; p = 0,002) et plus susceptible d' tre de sexe masculin (80,3% c. 74,4%; p = 0,040) et de pr senter des indices de gravit des blessures plus lev s (12,3 c. 8,3; p < 0,0001). La patient le de traumatologie provenant de milieux urbains tait plus susceptible d'avoir subi un traumatisme p n trant (42,5% c. 28,5%; p < 0,0001). Nous n'avons observ aucune diff rence aux plans de la morbidit et de la mortalit entre les 2 groupes, mais la dur e m diane du s jour hospitalier du groupe provenant de milieux ruraux a t plus longue (5 c. 3 j; p < 0,0007). Conclusion: M me si nous avons observ des diff rences cl s aux plans des donn es d mographiques ainsi que du type et de la gravit des blessures, les param tres se sont r v l s assez semblables entre les patient les de traumatologie des milieux urbains et ruraux. Cette observation se d marque de celles d' tudes canadiennes et am ricaines comparables, ce qui pourrait s'expliquer par l'exclusion de la mortalit pr hospitali re dans le groupe de milieux ruraux. La dur e plus longue du s jour chez la patient le de traumatologie de milieux ruraux pourrait tre attribuable des enjeux relatifs l' tat de ces malades au moment de leur cong ., The province of Saskatchewan, Canada, has a geographically dispersed population, with about 60% living more than an hour away from a tertiary care centre and 48% living more than an [...]

BACKGROUND: Midlife residential exposure to greenspace may slow cognitive decline by increasing opportunities for physical activity and social connection, restoring attention, or reducing stress or adverse environmental exposures. However, prospective studies on the association between greenness and cognitive decline are sparse. OBJECTIVE: We investigated the prospective association between greenness at midlife and cognitive decline later in life. We explored effect measure modification by apolipoprotein E (APOE)-E4 carrier status, neighborhood socioeconomic status (NSES), and rural/urban regions. METHODS: The Nurses' Health Study (N = 121,700) started in 1976 with married female nurses, 30-55 years of age, located across 11 US states. We examined 16,962 nurses who were enrolled in a substudy starting in 1995-2001 (mean age = 74 y) through 2008. We assessed average summer residential greenness in a 270-m buffer using Landsat Normalized Difference Vegetation Index data from 1986-1994. Starting in 1995-2001, participants underwent up to four repeated measures of five cognitive tests. A global composite score was calculated as the average of all z-scores for each task to evaluate overall cognition. We used linear mixed models to evaluate the association of average greenness exposure at midlife with cognitive decline in later life, adjusted for age, education, NSES, and depression. RESULTS: In adjusted models, higher midlife greenness exposure [per interquartile range (IQR): 0.18] was associated with a 0.004-unit (95% CI: 0.001, 0.006) slower annual rate of cognitive decline. For comparison, we found that 1 year of age is related to a -0.006 mean annual difference for global cognition in the full sample; thus, higher midlife greenness appeared equivalent to slowing cognitive decline by ~ 8 months. In analysis exploring gene--environment interactions, we found that among APOE-E4 carriers, an IQR increase in greenness was associated with a rate of decline that was slower by 0.01 units of global composite score (95% CI: 0.0004, 0.02). This association was attenuated among APOE-E4 noncarriers. We did not observe associations between greenness and baseline or annual rate of cognitive decline of verbal memory. DISCUSSION: Higher midlife greenness exposure is associated with slower cognitive decline later in life. Future research is necessary to confirm these findings. https://doi.org/10.1289/EHP13588, Introduction Literature has suggested that Alzheimer's disease and related dementia (ADRD), the seventh leading cause of death in the United States, (1) may begin [greater than or equal to]20 y [...]

I began my career when the major treatments for schizophrenia were haloperidol and chlorpromazine. Since then, treatments for schizophrenia have improved slowly and incrementally, especially when looking back in the [...]

BACKGROUND: Accumulating evidence suggests that domestic water hardness is linked to health outcomes, but its association to all-cause and cause-specific cancers warrants investigation. OBJECTIVE: The aim of this study was to investigate the association of domestic hard water with all-cause and cause-specific cancers. METHODS: In the prospective cohort study, a total of 447,996 participants from UK Biobank who were free of cancer at baseline were included and followed up for 16 y. All-cause and 22 common cause-specific cancer diagnoses were ascertained using hospital inpatient records and self-reported data until 30 November 2022. Domestic water hardness, measured by CaC[O.sub.3] concentrations, was obtained from the local water supply companies across England, Scotland, and Wales in 2005. Data were analyzed using Cox proportional hazard models, with adjustments for known measured confounders, including demographic, socioeconomic, clinical, biochemical, lifestyle, and environmental factors. RESULTS: Over a median follow-up of 13.6 y (range: 12.7-14.4 y), 58,028 all-cause cancer events were documented. A U-shaped relationship between domestic water hardness and all-cause cancers was observed (p for nonlinearity 60-120 mg/L), 0.88 (95% CI: 0.84, 0.91) for those exposed to hard water (>120-180 mg/L) and 1.06 (95% CI: 1.04, 1.08) for those exposed to very hard water (>180 mg/L). Additionally, domestic water hardness was associated with 11 of 22 cause-specific cancers, including cancers of the esophagus, stomach, colorectal tract, lung, breast, prostate, and bladder, as well as non-Hodgkin lymphoma, multiple myeloma, malignant melanoma, and hematological malignancies. Moreover, we observed a positive linear relationship between water hardness and bladder cancer. DISCUSSION: Our findings suggest that domestic water hardness was associated with all-cause and multiple cause-specific cancers. Findings from the UK Biobank support a potentially beneficial association between hard water and the incidence of all-cause cancer. However, very hard water may increase the risk of all-cause cancer. https://doi.org/10.1289/EHP13606, Introduction Cancer is a leading cause of mortality worldwide in 2020, nearly 10 million deaths were due to cancer, accounting for approximately one-sixth of all deaths. (1-3) It is projected [...]

BACKGROUND: Overweight and obesity impose a considerable individual and social burden, and the urban environments might encompass factors that contribute to obesity. Nevertheless, there is a scarcity of research that takes into account the simultaneous interaction of multiple environmental factors. OBJECTIVES: Our objective was to perform an exposome-wide association study of body mass index (BMI) in a multicohort setting of 15 studies. METHODS: Studies were affiliated with the Dutch Geoscience and Health Cohort Consortium (GECCO), had different population sizes (688-141,825), and covered the entire Netherlands. Ten studies contained general population samples, others focused on specific populations including people with diabetes or impaired hearing. BMI was calculated from self-reported or measured height and weight. Associations with 69 residential neighborhood environmental factors (air pollution, noise, temperature, neighborhood socioeconomic and demographic factors, food environment, drivability, and walkability) were explored. Random forest (RF) regression addressed potential nonlinear and nonadditive associations. In the absence of formal methods for multimodel inference for RF, a rank aggregation-based meta-analytic strategy was used to summarize the results across the studies. RESULTS: Six exposures were associated with BMI: five indicating neighborhood economic or social environments (average home values, percentage of high-income residents, average income, livability score, share of single residents) and one indicating the physical activity environment (walkability in 5-km buffer area). Living in high-income neighborhoods and neighborhoods with higher livability scores was associated with lower BMI. Nonlinear associations were observed with neighborhood home values in all studies. Lower neighborhood home values were associated with higher BMI scores but only for values up to [euro]300,000. The directions of associations were less consistent for walkability and share of single residents. DISCUSSION: Rank aggregation made it possible to flexibly combine the results from various studies, although between-study heterogeneity could not be estimated quantitatively based on RF models. Neighborhood social, economic, and physical environments had the strongest associations with BMI. https://doi.org/10.1289/EHP13393, Introduction Overweight and obesity impose a considerable individual and social burden, with global rates that have nearly tripled since 1975. (1) This striking rise could be attributed to changes in [...]

BACKGROUND: Evidence linking gaseous air pollution to late-life brain health is mixed. OBJECTIVE: We explored associations between exposure to gaseous pollutants and brain magnetic resonance imaging (MRI) markers among Atherosclerosis Risk in Communities (ARIC) Study participants, with attention to the influence of exposure estimation method and confounding by site. METHODS: We considered data from 1,665 eligible ARIC participants recruited from four US sites in the period 1987-1989 with valid brain MRI data from Visit 5 (2011-2013). We estimated 10-y (2001-2010) mean carbon monoxide (CO), nitrogen dioxide (N[O.sub.2]), nitrogen oxides (N[O.sub.x]), and 8-and 24-h ozone ([O.sub.3]) concentrations at participant addresses, using multiple exposure estimation methods. We estimated site-specific associations between pollutant exposures and brain MRI outcomes (total and regional volumes; presence of microhemorrhages, infarcts, lacunes, and severe white matter hyperintensities), using adjusted linear and logistic regression models. We compared meta-analytically combined site-specific associations to analyses that did not account for site. RESULTS: Within-site exposure distributions varied across exposure estimation methods. Meta-analytic associations were generally not statistically significant regardless of exposure, outcome, or exposure estimation method; point estimates often suggested associations between higher N[O.sub.2] and N[O.sub.x] and smaller temporal lobe, deep gray, hippocampal, frontal lobe, and Alzheimer disease signature region of interest volumes and between higher CO and smaller temporal and frontal lobe volumes. Analyses that did not account for study site more often yielded significant associations and sometimes different direction of associations. DISCUSSION: Patterns of local variation in estimated air pollution concentrations differ by estimation method. Although we did not find strong evidence supporting impact of gaseous pollutants on brain changes detectable by MRI, point estimates suggested associations between higher exposure to CO, N[O.sub.x], and N[O.sub.2] and smaller regional brain volumes. Analyses of air pollution and dementia-related outcomes that do not adjust for location likely underestimate uncertainty and may be susceptible to confounding bias. https://doi.org/10.1289/EHP13906, Introduction Growing evidence links air pollution to late-life cognitive health. Currently, the strongest evidence supports an effect of particulate matter (PM) air pollution. (1) In comparison with PM, fewer studies [...]

BACKGROUND: Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate various stress responses by regulating the transcription of a variety of antioxidant and cytoprotective genes, they play distinct roles in bone metabolism and remodeling. However, the precise roles of both transcription factors in bone loss induced by prolonged Cd exposure remain unclear. OBJECTIVES: We aimed to understand the molecular mechanisms underlying Cd-induced bone loss, focusing mainly on the roles of NRF2 and NRF1 in osteoclastogenesis provoked by Cd. METHODS: Male wild-type (WT), global Nrf2-knockout (Nrf[2.sup.-/-]) and myeloid-specific Nrf2 knockout [Nrf2(M)-KO] mice were administered Cd (50 or 100 ppm) via drinking water for 8 or 16 wk, followed by micro-computed tomography, histological analyses, and plasma biochemical testing. Osteoclastogenesis was evaluated using bone marrow-derived osteoclast progenitor cells (BM-OPCs) and RAW 264.7 cells in the presence of Cd (10 or 20 nM) with a combination of genetic and chemical modulations targeting NRF2 and NRF1. RESULTS: Compared with relevant control mice, global Nrf[2.sup.-/-] or Nrf2(M)-KO mice showed exacerbated bone loss and augmented osteoclast activity following exposure to 100ppm Cd in drinking water for up to 16 wk. In vitro osteoclastogenic analyses suggested that Nrf2-deficient BM-OPCs and RAW 264.7 cells responded more robustly to low levels of Cd (up to 20 nM) with regard to osteoclast differentiation compared with WT cells. Further mechanistic studies supported a compensatory up-regulation of long isoform of NRF1 (L-NRF1) and subsequent induction of nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 (NFATc1) as the key molecular events in the Nrf2 deficiency-worsened and Cd-provoked osteoclastogenesis. L-Nrf1 silenced (via lentiviral means) Nrf2-knockdown (KD) RAW cells exposed to Cd showed dramatically different NFATc1 and subsequent osteoclastogenesis outcomes compared with the cells of Nrf2-KD alone exposed to Cd, suggesting a mitigating effect of the Nrf1 silencing. In addition, suppression of reactive oxygen species by exogenous antioxidants N-acetyl-L-cysteine (2mM) and mitoquinone mesylate (MitoQ; 0.2 [micro]M) mitigated the L-NRF1-associated effects on NFATc1-driven osteoclastogenesis outcomes in Cd-exposed Nrf2-KD cells. CONCLUSIONS: This in vivo and in vitro study supported the authors' hypothesis that Cd exposure caused bone loss, in which NRF2 and L-NRF1 responded to Cd and osteoclastogenic stimuli in a cooperative, but contradictive, manner to coordinate Nfatc1 expression, osteoclastogenesis and thus bone homeostasis. Our study suggests a novel strategy targeting NRF2 and L-NRF1 to prevent and treat the bone toxicity of Cd. https://doi.org/10.1289/EHP13849, Introduction Cadmium (Cd), a nonessential heavy metal, is considered as one of the most toxic environmental and occupational hazards. (1) Human long-term exposure to Cd, which occurs mainly from consumption [...]

BACKGROUND: The potential health benefits of exposure to vegetation, or greenness, are well documented, but there are few nationwide studies in Brazil, a country facing challenges related to land-use planning, deforestation, and environmental health risks. OBJECTIVES: In this study, we investigated the association between greenness and hospitalizations for cardiorespiratory diseases in Brazil. METHODS: We accessed hospital admissions data from 967,771 postal codes (a total of 26,724,624 admissions) covering Brazil for the period between 2008 and 2018. We used Normalized Difference Vegetation Index (NDVI) data from the Moderate Resolution Imaging Spectroradiometer (MODIS) to measure greenness at the postal-code level. First, we applied a quasi-Poisson regression model to estimate the association between greenness and hospitalizations for circulatory and respiratory diseases, adjusted for air pollution, weather variables, and area-level socioeconomic status. We stratified the analyzes by sex, age group, health outcome, and Brazilian regions. In the second stage, we performed a meta-analysis to estimate pooled effects across the Brazilian regions. RESULTS: The national meta-analysis for the whole population, incorporating both urban and nonurban areas, showed that higher levels of greenness were associated with a lower risk of hospitalizations for circulatory diseases. An interquartile range (IQR = 0:18) increase in average NDVI was associated with a 17% (95% confidence interval: 8%, 27%) lower risk of cardiovascular admissions. In contrast, there was no association found between greenness and respiratory admissions. When specifically examining urban areas, the results remained consistent with the overall findings. However, the analyses of nonurban areas revealed divergent results, suggesting that higher levels of greenness in rural regions are associated with a lower risk of hospital admissions for both circulatory and respiratory diseases. DISCUSSION: The findings emphasize the importance of prioritizing the preservation and creation of green spaces in urban areas as a means of promoting cardiovascular health in Brazil. https://doi.org/10.1289/EHP13442, Introduction Cardiovascular and respiratory diseases are the leading causes of morbidity and mortality worldwide. (1) In Brazil, these diseases are responsible for a significant number of hospital admissions and deaths. [...]

Background: The evidence on the benefits and drawbacks of involving neurosurgical residents in the care of patients who undergo neurosurgical procedures is heterogeneous. We assessed the effect of neurosurgical residency programs on the outcomes of such patients in a large single-payer public health care system. Methods: Ten population-based cohorts of adult patients in Ontario who received neurosurgical care from 2013 to 2017 were identified on the basis of procedural codes, and the cohorts were followed in administrative health data sources. Patient outcomes by the status of the treating hospital (with or without a neurosurgical residency program) within each cohort were compared with models adjusted for a priori confounders and with adjusted multilevel models (MLMs) to also account for hospital-level factors. Results: A total of 46 608 neurosurgical procedures were included. Operative time was 8%-30% longer in hospitals with neurosurgical residency programs in 9 out of 10 cohorts. Thirty-day mortality was lower in hospitals with neurosurgical residency programs for aneurysm repair (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.20-0.44), cerebrospinal fluid shunting (OR 0.52, 95% CI 0.34-0.79), intra cerebral hemorrhage evacuation (OR 0.66, 95% CI 0.52-0.84), and posterior lumbar decompression (OR 0.32, 95% CI 0.15-0.65) in adjusted models. The mortality rates remained significantly different only for aneurysm repair (OR 0.19, 95% CI 0.05-0.69) and cerebrospinal shunting (OR 0.42, 95% CI 0.21-0.85) in MLMs. Length of stay was mostly shorter in hospitals with neurosurgical residents, but this finding did not persist in MLMs. Thirty-day reoperation rates did not differ between hospital types in MLMs. For 30-day readmission rates, only extracerebral hematoma decompression was significant in MLMs (OR 1.41, 95% CI 1.07-1.87). Conclusion: Hospitals with neurosurgical residents had longer operative times with similar to better outcomes. Most, but not all, of the differences between hospitals with and without residency programs were explained by hospital-level variables rather than direct effects of residents. Contexte : Les donn es relatives aux avantages et aux inconv nients de la participation des r sidentes et r sidents en neurochirurgie aux interventions de cette sp cialit sont h t rog nes. Nous avons valu l'effet des programmes de r sidence en neurochirurgie sur les r sultats chez les malades concern s au sein d'un volumineux syst me de sant universel payeur unique. M thodes : Dix cohortes populationnelles compos es de malades adultes ayant re u des soins en neurochirurgie en Ontario entre 2013 et 2017 ont t identif es partir des codes d'acte, et suivies au moyen des bases de donn es administratives sur la sant . Les r sultats chez les malades de chaque cohorte selon le statut de leur h pital (offrant ou non un programme de r sidence en neurochirurgie) ont t compar s des mod les ajust s pour tenir compte de variables de confusion a priori, et des mod les multiniveaux ajust s (MMN) pour tenir compte aussi de facteurs propres aux h pitaux. En tout, nous avons inclus 46 608 interventions neurochirurgicales. Le temps op ratoire a t 8%-30% plus long dans les h pitaux offrant un programme de r sidence en neurochirurgie dans 9 cohortes sur 10. La mortalit 30 jours a t moindre dans les h pitaux offrant un programme de r sidence en neuro chirurgie pour les r parations d'an vrisme (rapport des cotes [RC] 0,30, intervalle de confance [IC] de 95% 0,20-0,44), les d rivations du liquide c phalorachidien (RC 0,52, IC de 95% 0,34-0,79), le drainage des h morragies intrac r brales (RC 0,66, IC de 95% 0,52-0,84) et la d compression post rieure lombaire (RC 0,32, IC de 95% 0,15-0,65) dans les mod les ajust s. Les taux de mortalit sont demeur s significativement diff rents uniquement pour les r parations d'an vrisme (RC 0,19, IC de 95% 0,05-0,69) et les d rivations du liquide c phalorachidien (RC 0,42, IC de 95% 0,21-0,85) dans les MMN. La dur e des s jours a t majoritairement moindre dans les h pitaux offrant un programme de r sidence en neurochirurgie, mais cette observation ne se maintenait pas dans les MMN. Les taux de r intervention 30 jours n'ont pas diff r entre les types d'h pitaux dans les MMN. Les taux de r admission 30 jours n'ont t significatifs que pour les cas de d compression d'h matomes extrac r braux dans les MMN (RC 1,41, IC de 95% 1,07-1,87). Conclusion : Les temps op ratoires ont t plus longs dans les h pitaux offrant un programme de r sidence en neurochirurgie, et les r sultats ont t similaires ou meilleurs. La plupart des diff rences entre les h pitaux offrant ou non un programme de r sidence en neurochirurgie ont pu s'expliquer par des variables propres aux h pitaux plus que par un quelconque effet direct des programmes de r sidence en neurochirurgie., Evidence from studies that have examined resident influence on the outcome of surgical procedures, in general, is heterogenous. (1-6) This is expected because of the different natures and complexities of [...]

Hantaviruses are a large group of rodentborne single-stranded RNA viruses that cause clinical illness of varying severity in humans. Austria, and especially its southernmost federal states (Styria, Carinthia, and Burgenland), [...]

In 1926, A.C. Chandler described "a new schistosome infection of man" based on the presence of distinctive terminal spined schistosome eggs from 2 human fecal samples collected in Krishnanagar, West [...]

SARS-CoV-2 is characterized by diverse variants (1) with differing transmissibility and disease severity (2). The rapid evolution and spread of new variants has required a nimble public health response to [...]

Chronic wasting disease (CWD) is a member of the prion family of fatal, infectious neurodegenerative diseases. CWD affects cervids, such as moose, elk, and several species of deer, across much [...]

Human parainfluenza virus (HPIV) is a major cause of acute respiratory tract infections, such as croup in children and pneumonia in immunocompromised patients (1). HPIV is a single-stranded, enveloped RNA [...]

If a fresh brain is cut in half, two blue spots can be observed in the brainstem: the locus coeruleus (LC), or "sky-blue place." This bilateral nucleus was first described [...]

Introduction Sarcoidosis is a multiorgan inflammatory disease characterized by the formation of granulomas, which are spatially organized clusters of immune cells, in peripheral organs including the lung, skin, and bone [...], Sarcoidosis is an inflammatory disease characterized by immune cell-rich granulomas that form in multiple organs. In this issue of the JCI, Sati and colleagues used scRNA-seq and spatial transcriptomics of skin samples from patients with sarcoidosis and non-sarcoidosis granulomatous disease to identify upregulation of a stromal-immune CXCL12/CXCR4 axis and accumulation of type 1 innate lymphoid cells (ILC1s) in sarcoidosis. The accumulation of ILC1s in skin and blood was specific to patients with sarcoidosis and not observed in other granulomatous diseases. The authors used a mouse model of lung granuloma to show that ILCs contribute to granuloma formation and that blockade of CXCR4 reduced the formation of granulomas, providing a proof of concept that sarcoidosis may be treated by CXCR4 blockade to prevent the progression of disease in patients. These results suggest ILC1s could serve as a diagnostic biomarker in sarcoidosis and a potential therapeutic target.

The importance of context Obesity is a driver of diverse pathologies, including cardiometabolic diseases and cancer, with endometrial cancer being among the most strongly associated (1, 2). However, the excess [...], Obesity is a known driver of endometrial cancer. In this issue of the JCI, Gomez-Banoy and colleagues investigated a cohort of patients with advanced endometrial cancer treated with immune checkpoint inhibitors targeting the interaction between programmed cell death receptor-1 (PD-1) and its ligand (PD-L1). Notably, a BMI in the overweight or obese range was paradoxically associated with improved progression-free and overall survival. A second paradox emerged from CT analyses of visceral adipose tissue, viewed as an unhealthy fat depot in most other contexts, the quantity of which was also associated with improved treatment outcomes. Though visceral adiposity may have value as a biomarker to inform personalized treatment strategies, of even greater impact would be if a therapeutic strategy emerges from the future identification of adipose- derived mediators of this putative anticancer immune-priming effect.

Introduction Xerostomia, the subjective feeling of dry mouth typically accompanied by hyposalivation (1-3), is a common but often overlooked condition that can profoundly impair an individual's quality of life. Xerostomia [...], Salivary gland dysfunction is a common side effect of cancer treatments. Salivary function plays key roles in critical daily activities. Consequently, changes in salivary function can profoundly impair quality of life for cancer patients. We discuss salivary gland anatomy and physiology to understand how anticancer therapies such as chemotherapy, bone marrow transplantation, immunotherapy, and radiation therapy impair salivary function. We discuss approaches to quantify xerostomia in the clinic, including the advantages and limitations of validated quality-of-life instruments and approaches to directly measuring salivary function. Current and emerging approaches to treat cancer therapy-induced dry mouth are presented using radiation-induced salivary dysfunction as a model. Limitations of current sialagogues and salivary analogues are presented. Emerging approaches, including cellular and gene therapy and novel pharmacologic approaches, are described.

Following the acquisition of oncogenic mutations, cells undergo senescence and acquire heightened secretory states termed senescence-associated secretory phenotypes (SASPs). Proteins identified in SASPs include a broad range of inflammatory and [...]

Introduction Most kidney diseases are associated with the dysfunction of the glomerular filtration barrier (GFB), which comprises 3 layers, including the glomerular endothelial cells (GEC), the glomerular basement membrane (GBM) [...], Adeno-associated virus (AAV) is a promising in vivo gene delivery platform showing advantages in delivering therapeutic molecules to difficult or undruggable cells. However, natural AAV serotypes have insufficient transduction specificity and efficiency in kidney cells. Here, we developed an evolution-directed selection protocol for renal glomeruli and identified what we believe to be a new vector termed AAV2-GEC that specifically and efficiently targets the glomerular endothelial cells (GEC) after systemic administration and maintains robust GEC tropism in healthy and diseased rodents. AAV2-GEC-mediated delivery of IdeS, a bacterial antibody-cleaving proteinase, provided sustained clearance of kidney-bound antibodies and successfully treated antiglomerular basement membrane glomerulonephritis in mice. Taken together, this study showcases the potential of AAV as a gene delivery platform for challenging cell types. The development of AAV2-GEC and its successful application in the treatment of antibody-mediated kidney disease represents a significant step forward and opens up promising avenues for kidney medicine.

IntroductionPatients with Tuberculosis (TB) still have barriers in accessing high quality care and treatment services. In this qualitative study, we investigated barriers in accessing TB health services including confirmatory diagnosis, treatment adherence and recurrence of pulmonary TB using patients, physicians, and policy makers point of view.Materials and methodsIn this qualitative research from November to March 2021, 3 policy makers from the Ministry of Health, 12 provincial TB experts and physicians from the TB control program and 33 patients diagnosed with TB from 4 provinces were enrolled for a semi-structured in-depth interview. All interviews were audio recorded and then transcribed. Framework analysis was done by MAXQDA 2018 software to identify key themes.ResultsSeveral barriers reported for TB care and treatment: Poor knowledge of patents about TB symptoms, failure to screen for TB among at-risk patients by physicians, similar symptoms between TB and other lung diseases, low sensitivity of TB diagnostic tests, incomplete case finding and contact-tracing, stigma related to TB, and patients poor adherence due to long TB treatment. In addition, COVID-19 pandemic disrupted TB services and decreased detection, care and treatment services for TB patients.ConclusionOur findings highlight the need for interventions to increase public and healthcare providers awareness about TB symptoms, using more sensitive diagnostic tests, and interventions to reduce stigma, and improve case finding and contact tracing effort. Improving patients' adherence required better monitoring and shorter effective treatment regimes.