Risk factors common to leading eye health conditions and major non-communicable diseases: a rapid review and commentary

Background: To gain an understanding of the intersection of risk factors between the most prevalent eye health conditions that are associated with vision impairment and non-communicable diseases (NCDs). Methods: A series of rapid reviews of reviews reporting on non-modifiable risk factors, age and sex, and modifiable risk factors, including social determinants, were conducted for five common eye health conditions that are the leading causes of vision impairment globally (refractive error including uncorrected refractive error, cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy) and five prevalent NCDs (cancer, cardiovascular disease, chronic respiratory disease, dementia, and depressive disorders). Articles published within approximately 5 years to the end of 2019 were identified through expert recommendation, PubMED, Ovid Medline, the Lancet Global Burden of Disease series, the International Agency for Research on Cancer and World Cancer Research Fund.    Results: Of 9,213 records identified, 320 records were eligible. Eye health conditions and NCDs share many risk factors. Increased age was found to be the most common shared risk factor, associated with increased risks of AMD, cataract, diabetic retinopathy, glaucoma, refractive error, cancer, cardiovascular disease, chronic obstructive pulmonary disease, and dementia. Other shared risk factors included smoking, obesity, alcohol consumption (mixed results), and physical activity was protective, though limited evidence was found for eye conditions. Social determinants are well documented as risk factors for NCDs. Conclusion: There is substantial overlap in common established risk factors for the most frequent vision impairing eye conditions and leading NCDs. Increasing efforts should be made to integrate preventative and risk reduction interventions to improve health, with greatest shared benefits for initiatives which aim to reduce smoking, improve diet, and promote physical activity.</ns4:p

Risk factors common to leading eye health conditions and major non-communicable diseases: a rapid review and commentary

Background: To gain an understanding of the intersection of risk factors between the most prevalent eye health conditions that are associated with vision impairment and non-communicable diseases (NCDs). Methods: A series of rapid reviews of reviews reporting on non-modifiable risk factors, age and sex, and modifiable risk factors, including social determinants, were conducted for five common eye health conditions that are the leading causes of vision impairment globally (refractive error including uncorrected refractive error, cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy) and five prevalent NCDs (cancer, cardiovascular disease, chronic respiratory disease, dementia, and depressive disorders). Articles published within approximately 5 years to the end of 2019 were identified through expert recommendation, PubMED, Ovid Medline, the Lancet Global Burden of Disease series, the International Agency for Research on Cancer and World Cancer Research Fund.    Results: Of 9,213 records identified, 320 records were eligible. Eye health conditions and NCDs share many risk factors. Increased age was found to be the most common shared risk factor, associated with increased risks of AMD, cataract, diabetic retinopathy, glaucoma, refractive error, cancer, cardiovascular disease, chronic obstructive pulmonary disease, and dementia. Other shared risk factors included smoking, obesity, alcohol consumption (mixed results), and physical activity was protective, though limited evidence was found for eye conditions. Social determinants are well documented as risk factors for NCDs. Conclusion: There is substantial overlap in common established risk factors for the most frequent vision impairing eye conditions and leading NCDs. Increasing efforts should be made to integrate preventative and risk reduction interventions to improve health, with greatest shared benefits for initiatives which aim to reduce smoking, improve diet, and promote physical activity.</ns3:p

Visceral Leishmaniasis Relapse in Southern Sudan (1999–2007): A Retrospective Study of Risk Factors and Trends

Visceral leishmaniasis (kala-azar) caused by Leishmania donovani is spread from person to person by Phlebotomus sandflies. Major epidemics of visceral leishmaniasis have occurred in Southern Sudan during the 20th century. The worst of these killed 100,000 people in the western Upper Nile area of Southern Sudan from 1984–1994, a loss of one-third of the population. Médecins Sans Frontières has treated 40,000 kala-azar patients in Southern Sudan since the late 1980's. In this study we used routinely collected clinical data to investigate why some patients relapse after treatment. We found that patients with severely enlarged spleens (splenomegaly) are more likely to relapse. Patients treated for 17 days with a combination of two drugs (sodium stibogluconate and paromomycin) were more likely to relapse (but less likely to die) than patients treated for 30 days with a single drug (sodium stibogluconate). However, the transition from sodium stibogluconate to the sodium stibogluconate/paromomycin combination as standard treatment between 2001–2003 has not led to a significant increase in visceral leishmaniasis relapse

A modified Inflammatory Bowel Disease questionnaire and the Vaizey Incontinence questionnaire are simple ways to identify patients with significant gastrointestinal symptoms after pelvic radiotherapy

After radiotherapy for pelvic cancer, chronic gastrointestinal problems may affect quality of life (QOL) in 6–78% of patients. This variation may be due to true differences in outcome in different diseases, and may also represent the inadequacy of the scales used to measure radiotherapy-induced gastrointestinal side effects. The aim of this study was to assess whether outcome measures used for nonmalignant gastrointestinal disease are useful to detect gastrointestinal morbidity after radiotherapy. Results obtained from a Vaizey Incontinence questionnaire and a modified Inflammatory Bowel Disease questionnaire (IBDQ) – both patient completed – were compared to those from a staff administered Late Effects on Normal Tissue (LENT) – Subjective, Objective, Management and Analytic (SOMA) questionnaire in patients who had completed radiotherapy for a pelvic tumour at least 3 months previously. In all, 142 consecutive patients were recruited, 72 male and 70 female, median age 66 years (range 26–90 years), a median of 27 (range 3–258) months after radiotherapy. In total, 62 had been treated for a gynaecological, 58, a urological and 22, a gastrointestinal tract tumour. Of these, 21 had undergone previous gastrointestinal surgery and seven suffered chronic gastrointestinal disorders preceding their diagnosis of cancer. The Vaizey questionnaire suggested that 27% patients were incontinent for solid stools, 35% for liquid stools and 37% could not defer defaecation for 15 min. The IBDQ suggested that 89% had developed a chronic change in bowel habit and this change significantly affected 49% patients: 44% had more frequent or looser bowel movements, 30% were troubled by abdominal pain, 30% were troubled by bloating, 28% complained of tenesmus, 27% were troubled by their accidental soiling and 20% had rectal bleeding. At least 34% suffered emotional distress and 22% impairment of social function because of their bowels. The small intestine/colon SOMA median score was 0.1538 (range 0–1) and the rectal SOMA median score was 0.1428 (range 0–1). Pearson's correlations for the IBDQ score and small intestine/colon SOMA score was −0.630 (P<0.001), IBDQ and rectum SOMA −0.616 (P<0.001), IBDQ and Vaizey scores −0.599 (P<0.001), Vaizey and small intestine/colon SOMA 0.452 (P<0.001) and Vaizey and rectum SOMA 0.760 (P<0.001). After radiotherapy for a tumour in the pelvis, half of all patients develop gastrointestinal morbidity, which affects their QOL. A modified IBDQ and Vaizey questionnaire are reliable in assessing new gastrointestinal symptoms as well as overall QOL and are much easier to use than LENT SOMA

Tumor Growth Decreases NK and B Cells as well as Common Lymphoid Progenitor

Background: It is well established that chronic tumor growth results in functional inactivation of T cells and NK cells. It is less clear, however, whether lymphopoeisis is affected by tumor growth. Principal Findings: In our efforts of analyzing the impact of tumor growth on NK cell development, we observed a major reduction of NK cell numbers in mice bearing multiple lineages of tumor cells. The decrease in NK cell numbers was not due to increased apoptosis or decreased proliferation in the NK compartment. In addition, transgenic expression of IL-15 also failed to rescue the defective production of NK cells. Our systematic characterization of lymphopoeisis in tumor-bearing mice indicated that the number of the common lymphoid progenitor was significantly reduced in tumor-bearing mice. The number of B cells also decreased substantially in tumor bearing mice. Conclusions and Significance: Our data reveal a novel mechanism for tumor evasion of host immunity and suggest a new interpretation for the altered myeloid and lymphoid ratio in tumor bearing hosts

An eQTL Analysis of Partial Resistance to Puccinia hordei in Barley

Background - Genetic resistance to barley leaf rust caused by Puccinia hordei involves both R genes and quantitative trait loci. The R genes provide higher but less durable resistance than the quantitative trait loci. Consequently, exploring quantitative or partial resistance has become a favorable alternative for controlling disease. Four quantitative trait loci for partial resistance to leaf rust have been identified in the doubled haploid Steptoe (St)/Morex (Mx) mapping population. Further investigations are required to study the molecular mechanisms underpinning partial resistance and ultimately identify the causal genes.Methodology/Principal Findings - We explored partial resistance to barley leaf rust using a genetical genomics approach. We recorded RNA transcript abundance corresponding to each probe on a 15K Agilent custom barley microarray in seedlings from St and Mx and 144 doubled haploid lines of the St/Mx population. A total of 1154 and 1037 genes were, respectively, identified as being P. hordei-responsive among the St and Mx and differentially expressed between P. hordei-infected St and Mx. Normalized ratios from 72 distant-pair hybridisations were used to map the genetic determinants of variation in transcript abundance by expression quantitative trait locus (eQTL) mapping generating 15685 eQTL from 9557 genes. Correlation analysis identified 128 genes that were correlated with resistance, of which 89 had eQTL co-locating with the phenotypic quantitative trait loci (pQTL). Transcript abundance in the parents and conservation of synteny with rice allowed us to prioritise six genes as candidates for Rphq11, the pQTL of largest effect, and highlight one, a phospholipid hydroperoxide glutathione peroxidase (HvPHGPx) for detailed analysis.Conclusions/Significance - The eQTL approach yielded information that led to the identification of strong candidate genes underlying pQTL for resistance to leaf rust in barley and on the general pathogen response pathway. The dataset will facilitate a systems appraisal of this host-pathogen interaction and, potentially, for other traits measured in this populatio

A Robust Statistical Method for Association-Based eQTL Analysis

Background: It has been well established that theoretical kernel for recently surging genome-wide association study (GWAS) is statistical inference of linkage disequilibrium (LD) between a tested genetic marker and a putative locus affecting a disease trait. However, LD analysis is vulnerable to several confounding factors of which population stratification is the most prominent. Whilst many methods have been proposed to correct for the influence either through predicting the structure parameters or correcting inflation in the test statistic due to the stratification, these may not be feasible or may impose further statistical problems in practical implementation. Methodology: We propose here a novel statistical method to control spurious LD in GWAS from population structure by incorporating a control marker into testing for significance of genetic association of a polymorphic marker with phenotypic variation of a complex trait. The method avoids the need of structure prediction which may be infeasible or inadequate in practice and accounts properly for a varying effect of population stratification on different regions of the genome under study. Utility and statistical properties of the new method were tested through an intensive computer simulation study and an association-based genome-wide mapping of expression quantitative trait loci in genetically divergent human populations. Results/Conclusions: The analyses show that the new method confers an improved statistical power for detecting genuin

Application of microarray technology in pulmonary diseases

Microarrays are a powerful tool that have multiple applications both in clinical and cell biology arenas of common lung diseases. To exemplify how this tool can be useful, in this review, we will provide an overview of the application of microarray technology in research relevant to common lung diseases and present some of the future perspectives

Down-Regulation of the Canonical Wnt β-Catenin Pathway in the Airway Epithelium of Healthy Smokers and Smokers with COPD

Background: The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process. We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state. Methodology/Principal Findings: Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD. Thirty-three of 56 known Wnt-related genes were expressed in the SAE. Wnt pathway downstream mediators b-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes. Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry. Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro. Conclusions/Significance: Smoking down-regulates the Wnt pathway in the human airway epithelium. In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway ma

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk