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Air pollution is linked to mortality and morbidity. Since humans spend nearly all their time indoors, improving indoor air quality (IAQ) is a compelling approach to mitigate air pollutant exposure. To assess interventions, relying on clinical outcomes may require prolonged follow-up, which hinders feasibility. Thus, identifying biomarkers that respond to changes in IAQ may be useful to assess the effectiveness of interventions.
We conducted a narrative review by searching several databases to identify studies published over the last decade that measured the response of blood, urine, and/or salivary biomarkers to variations (natural and intervention-induced) of changes in indoor air pollutant exposure.
Numerous studies reported on associations between IAQ exposures and biomarkers with heterogeneity across study designs and methods. This review summarizes the responses of 113 biomarkers described in 30 articles. The biomarkers which most frequently responded to variations in indoor air pollutant exposures were high sensitivity C-reactive protein (hsCRP), von Willebrand Factor (vWF), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 1-hydroxypyrene (1-OHP).
This review will guide the selection of biomarkers for translational studies evaluating the impact of indoor air pollutants on human health.
The prevalence of mental health conditions and national suicide rates are increasing in many countries. Lithium is widely and effectively used in pharmacological doses for the treatment and prevention of manic/depressive episodes, stabilising mood and reducing the risk of suicide. Since the 1990s, several ecological studies have tested the hypothesis that trace doses of naturally occurring lithium in drinking water may have a protective effect against suicide in the general population.
To synthesise the global evidence on the association between lithium levels in drinking water and suicide mortality rates.
The MEDLINE, Embase, Web of Science and PsycINFO databases were searched to identify eligible ecological studies published between 1 January 1946 and 10 September 2018. Standardised regression coefficients for total (i.e. both genders combined), male and female suicide mortality rates were extracted and pooled using random-effects meta-analysis. The study was registered with PROSPERO (CRD42016041375).
The literature search identified 415 articles; of these, 15 ecological studies were included in the synthesis. The random-effects meta-analysis showed a consistent protective (or inverse) association between lithium levels/concentration in publicly available drinking water and total (pooled β = −0.27, 95% CI −0.47 to −0.08; P = 0.006, I2 = 83.3%), male (pooled β = −0.26, 95% CI −0.56 to 0.03; P = 0.08, I2 = 91.9%) and female (pooled β = −0.13, 95% CI −0.24 to −0.02; P = 0.03, I2 = 28.5%) suicide mortality rates. A similar protective association was observed in the six studies included in the narrative synthesis, and subgroup meta-analyses based on the higher/lower suicide mortality rates and lithium levels/concentration.
This synthesis of ecological studies, which are subject to the ecological fallacy/bias, supports the hypothesis that there is a protective (or inverse) association between lithium intakes from public drinking water and suicide mortality at the population level. Naturally occurring lithium in drinking water may have the potential to reduce the risk of suicide and may possibly help in mood stabilisation, particularly in populations with relatively high suicide rates and geographical areas with a greater range of lithium concentration in the drinking water. All the available evidence suggests that randomised community trials of lithium supplementation of the water supply might be a means of testing the hypothesis, particularly in communities (or settings) with demonstrated high prevalence of mental health conditions, violent criminal behaviour, chronic substance misuse and risk of suicide.
To describe characteristics of self-identified popular diet followers and compare mean BMI across these diets, stratified by time following diet.
Cross-sectional, web-based survey administered in 2015.
Non-localised, international survey.
Self-selected followers of popular diets (n 9019) were recruited to the survey via social media and email announcements by diet community leaders, categorised into eight major diet groups.
General linear models were used to compare mean BMI among (1) short-term (<1 year) and long-term (≥1 year) followers within diet groups and (2) those identifying as ‘try to eat healthy’ (TTEH) to all other diet groups, stratified by time following the specific diet. Participants were 82 % female, 93 % White and 96 % non-Hispanic. Geometric mean BMI was lower (P < 0·05 for all) among longer-term followers (≥1 year) of whole food, plant-based (WFPB), vegan, whole food and low-carb diets compared with shorter-term followers. Among those following their diet for 1–5 years (n 4067), geometric mean BMI (kg/m2) were lower (P < 0·05 for all) for all groups compared with TTEH (26·4 kg/m2): WFPB (23·2 kg/m2), vegan (23·5 kg/m2), Paleo (24·6 kg/m2), vegetarian (25·0 kg/m2), whole food (24·6 kg/m2), Weston A. Price (23·5 kg/m2) and low-carb (24·7 kg/m2).
Our findings suggest that BMI is lower among individuals who made active decisions to adhere to a specific diet, particularly more plant-based diets and/or diets limiting highly processed foods, compared with those who simply TTEH. BMI is also lower among individuals who follow intentional eating plans for longer time periods.
Taphonomic processes are informative about the magnitude and timing of paleoecological changes but remain poorly understood with respect to freshwater invertebrates in spring-fed rivers and streams. We compared taphonomic alteration among freshwater gastropods in live, dead (surficial shell accumulations), and fossil (late Pleistocene–early Holocene in situ sediments) assemblages from two Florida spring-fed systems, the Wakulla and Silver/Ocklawaha Rivers. We assessed taphonomy of two gastropod species: the native Elimia floridensis (n = 2504) and introduced Melanoides tuberculata (n = 168). We quantified seven taphonomic attributes (aperture condition, color, fragmentation, abrasion, juvenile spire condition, dissolution, and exterior luster) and combined those attributes into a total taphonomic score (TT). Fossil E. floridensis specimens exhibited the greatest degradation (highest TT scores), whereas live specimens of both species were least degraded. Specimens of E. floridensis from death assemblages were less altered than fossil specimens of the same species. Within death assemblages, specimens of M. tuberculata were significantly less altered than specimens of E. floridensis, but highly degraded specimens dominated in both species. Radiocarbon dates on fossils clustered between 9792 and 7087 cal BP, whereas death assemblage ages ranged from 10,692 to 1173 cal BP. Possible explanations for the observed taphonomic patterns include: (1) rapid taphonomic shell alteration, (2) prolonged near-surface exposure to moderate alteration rates, and/or (3) introduction of reworked fossil shells into surficial assemblages. Combined radiocarbon dates and taphonomic analyses suggest that all these processes may have played a role in death assemblage formation. In these fluvial settings, shell accumulations develop as a complex mixture of specimens derived from multiple sources and characterized by multimillennial time-averaging. These findings suggest that, when available, fossil assemblages may be more appropriate than death assemblages for assessing preindustrial faunal associations and recent anthropogenic changes in freshwater ecosystems.
A common clinical indication for duodenal biopsy is the exclusion of coeliac disease / gluten sensitive enteropathy. However, a variety of inflammatory and infectious disorders may affect the duodenum, some of which are associated with subtle endoscopic findings. The indications for duodenal biopsy are often the same as the broader indications for upper gastrointestinal endoscopy and include chronic dyspepsia, unexplained anaemia, abdominal pain, bloating, nausea, and diarrhoea
Endoscopic findings associated with inflammatory duodenal biopsies range from normal-appearing duodenal mucosa to mild hyperaemia and congestion of the duodenal bulb to erosions, severe congestion, mucosal haemorrhage, mucosal contact bleeding, and luminal narrowing.
The lower gastrointestinal tract consists of ileum, vermiform appendix, colon, and rectum. The main epithelial cell types are absorptive cells, goblet cells, Paneth cells and endocrine cells. Structurally the ileum resembles the duodenum, and includes villi and crypts. Gut-associated lymphoid tissue plays an important role in immune defence and has focal and diffuse elements in the small bowel. Lymphoid tissue is particularly prominent in the most distal part of the ileum. The mucosa of the large bowel is less complex than that of the small bowel, with parallel crypts and a smooth surface. In the normal colorectal mucosa, the density of plasma cells is highest in the upper one third and lowest in the lower one third. Eosinophilia in the ileum and large bowel is difficult to diagnose unless numbers are greatly increased. There may be a few neutrophils in the normal lamina propria but intraepithelial neutrophils are very infrequent. Apoptosis is a normal finding but the number of well-developed crypt epithelial cell apoptosis should be small. The intraepithelial lymphocyte count in the ileum is 0-9 per 100 surface epithelial cells and in the colon 0-5 per 100. Knowledge of the range of normality is important and helps pathologists to avoid overdiagnosis of inflammatory changes and of neoplasia.
The upper gastrointestinal tract consists of oesophagus, stomach, and duodenum. These are distinct from one another histologically. The lining of the oesophagus consists mainly of non-keratinising stratified squamous epithelium, and there is a variable amount of columnar epithelium distally. The stomach has three main histological regions, which from proximal to distal are the cardia, the body/fundus, and the antrum. All of these regions include surface epithelial cells that extend downwards into foveolae. Beneath the foveolae are a short isthmic zone and a deeper glandular layer. In the body/fundus, the glandular layer is thicker and the glands are more closely packed than in the antrum. Parietal cells and chief cells are the main component of the body/fundus glands while in the antrum they are sparse. The gastric cardia is a short segment that usually lacks parietal and chief cells. In the normal state, columnar mucosa extends from the stomach upwards into the distal oesophagus for a variable length. In contrast, Barrett’s oesophagus is pathological replacement of the distal oesophageal mucosa by metaplastic columnar mucosa that may be gastric or intestinal. The duodenal mucosa includes villi and crypts, both lined by columnar absorptive cells. Other epithelial cell types include goblet cells and Paneth cells. Endocrine cells are present at all sites but are difficult to identify and sparse in the oesophagus.
Therapeutic radiation for cancer is more than 100 years old. Side effects constitute the main limitation to its use. Side effects may be acute or chronic, but these categories overlap. As cancer survival improves, chronic radiation damage becomes more common. The gastrointestinal (GI) tract, particularly the bowel, is particularly vulnerable because of its anatomical location and the rapidity of turnover of many GI epithelial cell types. Severity of radiation damage depends also on patient factors, chemotherapy, radiotherapy regimen, and organ mobility. Histologically, common mucosal changes include ulceration, acute inflammation, eosinophilic infiltrates, and architectural abnormalities. Fibrosis may occur later. Vascular changes are more common in chronic disease, affect deeper layers, and include ectasia, intimal thickening, fibrinoid change, thrombosis, and luminal obliteration. Atypia of epithelium, fibroblasts, and endothelium is common and can mimic neoplasia. Epithelial atypia has a lower nuclear:cytoplasmic ratio than dysplasia and matures towards the mucosal surface, aiding the distinction. Features sometimes resemble viral cytopathic change. Chronic radiation colitis may resemble inflammatory bowel disease, ischaemia, and mucosal prolapse while vascular changes may resemble amyloid. In summary, histological clues to radiation damage include fibrosis, atypical fibroblasts, eosinophilic infiltrates, and vascular changes. Confident diagnosis as radiation damage requires a clinical history but this may be unavailable, especially if decades have elapsed since therapy.
Biopsy assessment of chronic idiopathic inflammatory bowel disease (IBD) is important for diagnosis, classification, determination of activity, documentation of anatomical extent and distribution, detection of complications, and diagnosis and grading of dysplasia. In addition, it may predict treatment response, clinical behaviour after therapy, and risk of future dysplasia. Microscopic features favouring IBD over non-IBD in biopsies include basal plasmacytosis and crypt architectural changes. Typically, UC extends from the rectum proximally and in a continuous fashion, while Crohn’s disease is discontinuous with intervening areas of sparing. Microscopic features that distinguish most reliably between Crohn’s disease and UC include granulomas (strongly favouring Crohn’s disease) and the distribution of architectural abnormalities / chronic inflammation between sites and within sites. However, discontinuity may also occur in UC. A caecal “patch”, i.e. a discontinuous area of caecal inflammation, is common in UC. Rectal sparing and other forms of discontinuity are more frequent in longstanding UC than new UC. The label IBD unclassified (IBDU) is available for difficult cases. In very early IBD (i.e., symptoms for < 6 weeks), the architectural changes are often absent. IBD is common in patients with primary sclerosing cholangitis but may have unusual features. In summary, histological assessment in the light of the clinical and endoscopic findings plays an important role in optimising management of IBD.
Various intestinal and extraintestinal conditions may complicate IBD. Intestinal complications include infections, strictures, obstruction, fistulas, dysplasia, and malignancy. Extraintestinal complications or associations include cutaneous disease, arthropathy, ocular problems, primary sclerosing cholangitis, and other forms of liver disease. The intestinal complications whose diagnosis and assessment relies most heavily on histopathology are cytomegalovirus (CMV) infection, dysplasia, and malignancy. Reactivation of latent CMV is more likely in ulcerative colitis than Crohn’s disease, is more common in those with immunosuppression and/or severe disease, and is associated with a worse clinical outcome. CMV inclusions are often detectable on H&E examination. Immunohistochemistry for CMV is specific and sensitive. Histopathology may also play a role in recognising other infections such as amoebiasis and TB and may contribute to the assessment of fissures and fistulas. Confident recognition of dysplasia depends on histology, although endoscopic methods of detection are becoming more reliable. Colorectal carcinoma (CRC) is the most common malignancy to complicate IBD and is more likely than non-IBD CRC to present at a younger age and to be right-sided and is more likely to show signet ring cell differentiation, a peritumoral lymphocytic reaction, and a mucinous phenotype. Small bowel cancer may complicate Crohn’s disease but is rare overall. A lymphoproliferative disorder may complicate IBD, especially in the setting of thiopurine therapy.
Inflammatory bowel disease (IBD) typically involves the large bowel, small bowel (ileum / jejunum), or both. Involvement of the upper GI tract is less common, although its frequency is uncertain because common causes of inflammation such as gastro-oesophageal reflux and Helicobacter pylori infection also require exclusion. In the setting of known IBD, upper GI inflammation generally favours Crohn’s disease over ulcerative colitis (UC), while granulomas strongly suggest involvement by IBD and indicate Crohn’s disease rather than UC. New upper GI inflammation may raise the possibility of IBD, while unexplained new upper GI granulomas require exclusion of Crohn’s disease. Unfortunately, few histological patterns apart from granulomas are specific or discriminant. Lymphocytic oesophagitis is a poorly defined entity associated with IBD and/or Crohn’s disease in some studies. Focally enhanced gastritis (FEG), though initially regarded as typical of Crohn’s disease, probably has limited value apart from perhaps predicting IBD in children. Rarely, UC patients develop a duodenitis resembling the colorectal changes histologically. UC may also be associated, infrequently, with characteristic patterns of gastritis. Compared with adults, children with IBD are more likely to have upper GI involvement, to develop GI granulomas, and to undergo investigation for upper GI disease. Overall, upper GI granulomas assist with the diagnosis and classification of IBD but few other upper GI features are discriminatory between IBD and other causes or between UC and Crohn’s disease.
The term “dysplasia” refers to “an unequivocal neoplastic epithelial alteration without invasive growth”. The term “intraepithelial neoplasia” often replaces “dysplasia” in World Health Organisation (WHO) guidance. Dysplasia is a precursor lesion of cancer and a marker for high cancer risk, offering a window of opportunity for early detection and cure of neoplasia. Most pathologists now classify columnar dysplasia as low grade (LGD) and high grade (HGD). The criteria for grading dysplasia include both cytological and architectural abnormalities. The diagnosis of dysplasia can be challenging in some clinical settings, especially when there is a background of active or resolving inflammation [e.g. in Barrett’s oesophagus (BO) or inflammatory bowel disease (IBD)] that may cause reactive epithelial atypia. Additionally, there is significant inter- and intra-observer variability for the diagnosis and grading of dysplasia. The variability may reflect the limitations of morphology-based criteria and has led to the development of adjunctive diagnostic methods such as immunohistochemistry. These methods, although promising, are controversial and require evaluation in further studies. This chapter describes the classification, microscopic features, and grading of dysplasia at different sites in the gastrointestinal (GI) tract.
Gastrointestinal biopsies comprise a substantial minority of the workload of most histopathology departments. Assessment of IBD, whether new or longstanding, is among the more challenging tasks that face pathologists. Good quality histopathology reports enhance patient management by refining the diagnosis and classification of IBD and by documenting clearly the extent of disease, the degree of activity, the degree of dysplasia, and any complications such as CMV. In order to produce a good quality report, the pathologist should adopt both a systematic approach to assessment and a well-defined structure for the body and conclusion of the report. Adherence to a similar approach and structure by histopathologists working in different centres could help to improve consistency of reporting and allow better comparison between reports issued at different times and/or in different centres. The use of datasets and a simple proforma for IBD pathology reporting should also increase the degree of conformity between centres.