Characterization of BaiH: A Clostridium scindens Gene Product That Metabolizes Bile Acids to Yield Cancer-Linked Products

Bile acids, hydrophobic molecules produced from cholesterol by the liver, allow for metabolization of lipids and lipid-soluble vitamins from the human diet. While mostly reabsorbed by the gastrointestinal pathway after carrying out their purpose, some bile acids continue through the digestive tract and interact with microorganisms in the large intestine. Species in the Clostridia genus have exhibited conversion of these primary bile acids into secondary bile acids via a 7ɑ-dehydroxylation pathway; the presence of these secondary bile acids has been linked to colon cancer, among other diseases. The bile acid-inducible (bai) operon has been characterized in Clostridia and is known to produce enzymes responsible for this conversion. The oxidative portion of this enzymatic pathway is not fully understood, although the putative genes and their associated gene products have been identified. The purpose of this research is to determine the 3-dimensional structure of the enzyme produced by baiH, and to subsequently characterize the bile acid dehydrogenase this DNA encodes. A plasmid vector containing baiH was transformed into E. coli, and gene overexpression was induced with IPTG at the mid-log phase. A HiTrap TALON crude column and a 200 pg Superdex column were used to purify the protein of interest. Immobilized metal affinity chromatography and size exclusion chromatography were shown to be effective in isolating and purifying the protein. This information is supported by gel electrophoresis. The purified protein was determined to be in concentration of 1.8 mg/mL. A homology model was generated using E. coli enzyme 2,4-dienoyl-CoA reductase as a template. Conserved residues participating in the oxidation of the bile acid-CoA intermediate include Arg-214 and Tyr-166. Both of these residues are vital in orienting the substrate and cofactors FMN and FAD

1985 Minnesota Citizen Opinions on Public Education and Educational Reform.

The results of a statewide survey of 2,000 adults in the spring of 1985 indicate that Minnesotans are concerned about primary and secondary education and are willing to spend money to improve the schools, especially equal access to quality education. They want schools to be accountable through published results of standardized tests and they reject the concept of open enrollment.CURA/College of Education Project on The Future of K-12 Public Education in Minnesota

Factors associated with self-reported health among New Zealand military veterans: a cross-sectional study

Objective To identify factors associated with better or poorer self-reported health status in New Zealand military Veterans. Design A cross-sectional survey. Participants The participants of interest were the 3874 currently serving Veterans who had been deployed to a conflict zone, but all Veterans were eligible to participate. Study variables The EQ-5D-5L, asking about problems across five dimensions (mobility, self-care, usual activities, pain or discomfort and anxiety or depression), with five levels of severity (eg, no, slight, moderate, severe or extreme problems), also containing a Visual Analogue Scale (EQ-VAS) to self-assess health state, scaled from 0 (worst) to 100 (best) imagined health. Hypothetical relationships with better health were positive social support, sleep and psychological flexibility; with poorer health, post-traumatic stress, exposure to psychological trauma, distress and hazardous drinking. Results The EQ5-D-5L was completed by 1767 Veterans, 1009 serving, a response rate of 26% from that group, 1767 completing the EQ5-D, 1458 who had deployed, 288 who had not and the 21 who did not provide deployment data. Of these, 247 were not used in the analysis due to missing values in one or more variables, leaving 1520 for analysis. A significantly higher proportion of Veterans reported ‘any problems’ rather than ‘no problems’ with four EQ-5D dimensions: mobility, self-care, usual activities and pain or discomfort, but no difference in anxiety or depression. Age, length of service, deployment, psychological flexibility and better sleep quality were associated with higher EQ-VAS scores; distress with lower EQ-VAS scores. Conclusion In this sample of New Zealand Veterans, psychological flexibility and good sleep are associated with better self-rated health, and distress and poor sleep with diminished health. These factors might be used as sentinel health indicators in assessing Veteran health status, and cognitive–behavioural therapy encompassing these domains may be useful in improving the health of New Zealand Veterans

Prevalence and alternative explanations influence cancer diagnosis: An experimental study with physicians.

Objective: Cancer causes death to millions of people worldwide. Early detection of cancer in primary care may enhance patients’ chances of survival. However, physicians often miss early cancers, which tend to present with undifferentiated symptoms. Within a theoretical framework of the hypothesis generation (HyGene) model, together with psychological literature, we studied how 2 factors—cancer prevalence and an alternative explanation for the patient’s symptoms—impede early cancer detection, as well as prompt patient management. Method: Three hundred family physicians diagnosed and managed 2 patient cases, where cancer was a possible diagnosis (one colorectal cancer, the other lung cancer). We employed a 2 (cancer prevalence: low vs. high) × 2 (alternative explanation: present vs. absent) between-subjects design. Cancer prevalence was manipulated by changing either patient age or sex; the alternative explanation for the symptoms was manipulated by adding or removing a relevant clinical history. Each patient consulted twice. Results: In a series of random-intercept logistic models, both higher prevalence (OR = 1.92, 95% confidence interval [CI 1.27, 2.92]) and absence of an alternative explanation (OR = 1.70, 95% CI [1.11, 2.59]) increased the likelihood of a cancer diagnosis, which, in turn, increased the likelihood of prompt referral (OR = 22.84, 95% CI [16.14, 32.32]). Conclusions: These findings confirm the probabilistic nature of the diagnosis generation process and validate the application of the HyGene model to early cancer detection. Increasing the salience of cancer—such as listing cancer as a diagnostic possibility—during the initial hypothesis generation phase may improve early cancer detection

Indigenous injury outcomes: Life satisfaction among injured Māori in New Zealand three months after injury

Background: Māori, the indigenous population of New Zealand, experience numerous and consistent health disparities when compared to non-Māori. Injury is no exception, yet there is a paucity of published literature that examines outcomes following a wide variety of injury types and severities for this population. This paper aims to identify pre-injury and injury-related predictors of life satisfaction three months after injury for a group of injured Māori. Methods: The Māori sample (n = 566) were all participants in the Prospective Outcomes of Injury Study (POIS). POIS is a longitudinal study of 2856 injured New Zealanders aged 18–64 years who were on an injury entitlement claims’ register with New Zealand’s no-fault compensation insurer. The well-known Te Whare Tapa Whā model of overall health and well-being was used to help inform the selection of post-injury life satisfaction predictor variables. Multivariable analyses were used to examine the relationships between potential predictors and life satisfaction. Results: Of the 566 Māori participants, post-injury life satisfaction data was available for 563 (99%) participants. Of these, 71% reported satisfaction with life three months after injury (compared to 93% pre-injury). Those with a higher injury severity score, not satisfied with pre-injury social relationships or poor self-efficacy pre-injury were less likely to be satisfied with life three months after injury. Conclusions: The large majority of Māori participants reported being satisfied with life three months after injury; however, nearly a third did not. This suggests that further research investigating outcomes after injury for Māori, and predictors of these, is necessary. Results show that healthcare providers could perhaps put greater effort into working alongside injured Māori who have more severe injuries, report poor self-efficacy and were not satisfied with their pre-injury social relationships to ensure increased likelihood of satisfaction with life soon after injury

Expectations for antibiotics increase their prescribing: Causal evidence about localized impact.

Objective: Clinically irrelevant but psychologically important factors such as patients' expectations for antibiotics encourage overprescribing. We aimed to (a) provide missing causal evidence of this effect, (b) identify whether the expectations distort the perceived probability of a bacterial infection either in a preor postdecisional distortions pathway, and (c) detect possible moderators of this effect. Method: Family physicians expressed their willingness to prescribe antibiotics (Experiment 1, n1 = 305) or their decision to prescribe (Experiment 2, n2 = 131) and assessed the probability of a bacterial infection in hypothetical patients with infections either with low or high expectations for antibiotics. Response order of prescribing/ probability was manipulated in Experiment 1. Results: Overall, the expectations for antibiotics increased intention to prescribe (Experiment 1, F(1, 301) = 25.32, p p 2 = .08, regardless of the response order; Experiment 2, odds ratio [OR] = 2.31, and OR = 0.75, Vignettes 1 and 2, respectively). Expectations for antibiotics did not change the perceived probability of a bacterial infection (Experiment 1, F(1, 301) = 1.86, p = .173, ηp 2 = .01, regardless of the response order; Experiment 2, d=-0.03, and d = +0.25, Vignettes 1 and 2, respectively). Physicians' experience was positively associated with prescribing, but it did not moderate the expectations effect on prescribing. Conclusions: Patients' and their parents' expectations increase antibiotics prescribing, but their effect is localized-it does not leak into the perceived probability of a bacterial infection. Interventions reducing the overprescribing of antibiotics should target also psychological factors

Indigenous injury outcomes: life satisfaction among injured Maori in New Zealand three months after injury

BACKGROUND: Māori, the indigenous population of New Zealand, experience numerous and consistent health disparities when compared to non-Māori. Injury is no exception, yet there is a paucity of published literature that examines outcomes following a wide variety of injury types and severities for this population. This paper aims to identify pre-injury and injury-related predictors of life satisfaction three months after injury for a group of injured Māori. METHODS: The Māori sample (n = 566) were all participants in the Prospective Outcomes of Injury Study (POIS). POIS is a longitudinal study of 2856 injured New Zealanders aged 18–64 years who were on an injury entitlement claims’ register with New Zealand’s no-fault compensation insurer. The well-known Te Whare Tapa Whā model of overall health and well-being was used to help inform the selection of post-injury life satisfaction predictor variables. Multivariable analyses were used to examine the relationships between potential predictors and life satisfaction. RESULTS: Of the 566 Māori participants, post-injury life satisfaction data was available for 563 (99%) participants. Of these, 71% reported satisfaction with life three months after injury (compared to 93% pre-injury). Those with a higher injury severity score, not satisfied with pre-injury social relationships or poor self-efficacy pre-injury were less likely to be satisfied with life three months after injury. CONCLUSIONS: The large majority of Māori participants reported being satisfied with life three months after injury; however, nearly a third did not. This suggests that further research investigating outcomes after injury for Māori, and predictors of these, is necessary. Results show that healthcare providers could perhaps put greater effort into working alongside injured Māori who have more severe injuries, report poor self-efficacy and were not satisfied with their pre-injury social relationships to ensure increased likelihood of satisfaction with life soon after injury

The Role of Physicians’ First Impressions in the Diagnosis of Possible Cancers without Alarm Symptoms

Background. First impressions are thought to exert a disproportionate influence on subsequent judgments; however, their role in medical diagnosis has not been systematically studied. We aimed to elicit and measure the association between first impressions and subsequent diagnoses in common presentations with subtle indications of cancer. Methods. Ninety UK family physicians conducted interactive simulated consultations online, while on the phone with a researcher. They saw 6 patient cases, 3 of which could be cancers. Each cancer case included 2 consultations, whereby each patient consulted again with nonimproving and some new symptoms. After reading an introduction (patient description and presenting problem), physicians could request more information, which the researcher displayed online. In 2 of the possible cancers, physicians thought aloud. Two raters coded independently the physicians’ first utterances (after reading the introduction but before requesting more information) as either acknowledging the possibility of cancer or not. We measured the association of these first impressions with the final diagnoses and management decisions. Results. The raters coded 297 verbalizations with high interrater agreement (Kappa = 0.89). When the possibility of cancer was initially verbalized, the odds of subsequently diagnosing it were on average 5 times higher (odds ratio 4.90 [95% CI 2.72 to 8.84], P &lt; 0.001), while the odds of appropriate referral doubled (OR 1.98 [1.10 to 3.57], P = 0.002). The number of cancer-related questions physicians asked mediated the relationship between first impressions and subsequent diagnosis, explaining 29% of the total effect. Conclusion. We measured a strong association between family physicians’ first diagnostic impressions and subsequent diagnoses and decisions. We suggest that interventions to influence and support the diagnostic process should target its early stage of hypothesis generation. </jats:p

Types and Patterns of Colonic Polyps Encountered at a Tertiary Care Center in a Developing Country in South Asia

Purpose. To identify the prevalence, types, and patterns of colonic polyps in a cohort of patients presenting to a tertiary care referral center in Sri Lanka. Methods. Endoscopy and pathology reports of a single unit from 2006 to 2013 were analyzed retrospectively. Spearman’s correlation coefficient and chi-square test were used to identify correlations. Results. There were a total of 158 patients (M : F, 10 : 57) who had polyps encountered on colonoscopy (n=1408) and flexible sigmoidoscopy (n=2402) with an incidence of 4.1%. Mean age was 56.5 years (SD 16.4) and the incidence of polyps increased with age. The majority (81.6%) had one polyp. A total of 188 polyps were assessed and most were seen in the rectum (33.5%) followed by sigmoid colon (22.9%). The commonest histological type was tubulovillous adenoma (33.5%) followed by tubular adenoma (24.5%). Most polyps were benign (91.5%). There was no statistically significant correlation with age or gender with malignancy, site, or histology. Discussion and Conclusion. The incidence of colorectal polyps was lower than the values reported in the west. More polyps were identified in males. There was no statistically significant association between age, gender, or multiplicity and malignant change in the polyps