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Para- #cresol production by #Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria

https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007191

C. difficile is transmitted by spores, which are able to survive in harsh environments for long periods of time. After initial treatment for C. difficile, up to 35% of patients develop the disease again, thus requiring additional and more successful treatment.

Here, we use novel techniques to show that C. difficile produces a compound, p-cresol, which has detrimental effects on the natural protective gut bacteria. We show that p-cresol selectively targets certain bacteria in the gut and disrupts their ability to grow.

By removing the ability of C. difficile to produce p-cresol, we show that it makes C. difficile less able to recolonise after an initial infection. This is linked to significant alterations in the natural healthy bacterial composition of the gut. Our study provides new insights into the effects of p-cresol production on the healthy gut microbiota and how it contributes to C. difficile survival and pathogenesis.

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Enhancement of the #gut barrier integrity by a microbial metabolite through the Nrf2 pathway

https://www.nature.com/articles/s41467-018-07859-7

The importance of gut #microbiota in human health and pathophysiology is undisputable. Despite the abundance of metagenomics data, the functional dynamics of gut microbiota in human health and disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics of berries and pomegranate fruits displays anti-inflammatory, anti-oxidative, and anti-ageing activities. Here, we show that UroA and its potent synthetic analogue (UAS03) significantly enhance gut barrier function and inhibit unwarranted inflammation.

Cumulatively, the results highlight how microbial metabolites provide two-pronged beneficial activities at gut epithelium by enhancing barrier functions and reducing inflammation to protect from colonic diseases.

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Emergency and Urgent #Hospitalizations Linked to Accelerated #Cognitive Decline in Older Adults

https://neurosciencenews.com/cognitive-decline-hospitalization-10521/

We found that those who have non-elective (emergency or urgent) hospitalizations and who have not previously been diagnosed with dementia or Alzheimer’s disease had a rapid decline in cognitive function (i.e., thinking abilities) compared to the prehospital rates

The data emerged from a study of 777 older adults (81 years old on average, 75 percent of them women) enrolled in the Rush Memory and Aging Project (MAP) in Chicago. The study involved annual cognitive assessments and clinical evaluations.

We saw a clear distinction: non-elective admissions drive the association between hospitalization and long-term changes in cognitive function in later life, while elective admissions do not necessarily carry the same risk of negative cognitive outcomes,” James said. “These findings have important implications for the medical decision making and care of older adults.

“While recognizing that all medical procedures carry some degree of risk, this study implies that planned hospital encounters may not be as dangerous to the cognitive health of older persons as emergency or urgent situations.

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Association of #Sleep Duration and Quality With Subclinical #Atherosclerosis

http://www.onlinejacc.org/content/73/2/134

Four groups were defined: very short sleep duration <6 h, short sleep duration 6 to 7 h, reference sleep duration 7 to 8 h, and long sleep duration >8 h. Sleep fragmentation index was defined as the sum of the movement index and fragmentation index.

When adjusted for conventional risk factors, very short sleep duration was independently associated with a higher atherosclerotic burden with 3-dimensional vascular ultrasound compared to the reference group (odds ratio: 1.27; 95% confidence interval: 1.06 to 1.52; p = 0.008). Participants within the highest quintile of sleep fragmentation presented a higher prevalence of multiple affected noncoronary territories (odds ratio: 1.34; 95% confidence interval: 1.09 to 1.64; p = 0.006). No differences were observed regarding coronary artery calcification score in the different sleep groups.

Conclusions Lower sleeping times and fragmented sleep are independently associated with an increased risk of subclinical multiterritory atherosclerosis. These results highlight the importance of healthy sleep habits for the prevention of cardiovascular disease.

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Excess Burden of #Mental Illness and Hospitalization in Young-Onset Type 2 #Diabetes: A Population-Based Cohort Study

http://annals.org/aim/article-abstract/2720956/excess-burden-mental-illness-hospitalization-young-onset-type-2-diabetes

Patients with YOD had the highest hospitalization rates by attained age. In the registry cohort, 36.8% of YOD bed-days before age 40 years were due to mental illness. The adjusted rate ratios showed increased hospitalization in YOD versus usual-onset T2D (onset at age ≥40 years) (all-cause, 1.8 95% CI, 1.7 to 2.0; renal, 6.7 CI, 4.2 to 10.6; diabetes, 3.7 CI, 3.0 to 4.6; cardiovascular, 2.1 CI, 1.8 to 2.5; infection, 1.7 CI, 1.4 to 2.1; P < 0.001 for all). Models estimated that intensified risk factor control in YOD (hemoglobin A1c level <6.2%, systolic blood pressure <120 mm Hg, low-density lipoprotein cholesterol level <2.0 mmol/L <77.3 mg/dL, triglyceride level <1.3 mmol/L <115.1 mg/dL, waist circumference of 85 cm men or 80 cm women, and smoking cessation) was associated with a one-third reduction in cumulative bed-days from onset to age 75 years (97 to 65 bed-days).

Adults with YOD have excess hospitalizations across their lifespan compared with persons with usual-onset T2D, including an unexpectedly large burden of mental illness in young adulthood. Efforts to prevent YOD and intensify cardiometabolic risk factor control while focusing on mental health are urgently needed

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Society of American Gastrointestinal and #Endoscopic Surgeons
Five Things Physicians and Patients Should Question

http://www.choosingwisely.org/societies/society-of-american-gastrointestinal-and-endoscopic-surgeons/

Don’t discharge patients presenting emergently with acute cholecystitis without first offering laparoscopic cholecystectomy.

Avoid routine cholecystectomy for patients with asymptomatic #cholelithiasis.

Avoid other imaging tests apart from ultrasound for the initial evaluation of patients with suspected gallstone disease.

Avoid the routine use of ultrasound in evaluating clinically apparent inguinal hernia.

Avoid opioid-only modalities for post-operative pain control.

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Impact of Cyclic Citrullinated Peptide Antibody Level on Progression to #Rheumatoid Arthritis in Clinically Tested #CCP‐Positive Patients Without RA

https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.23820

We identified 340 CCP+ patients who were without RA or other rheumatic disease at baseline. During 1047 person‐years of follow‐up, 73 (21.5%) patients developed RA. Risk of progression to RA increased with CCP level, with 46.0% (95%CI 34.7‐55.3) of high level CCP patients progressing to RA by 5 years. Compared to low CCP, medium (HR 3.00, 95%CI 1.32‐6.81) and high (HR 4.83, 95%CI 2.51‐9.31) CCP levels were strongly associated with progression to RA, adjusting for age, sex, body mass index, smoking, family history of RA, and rheumatoid factor level.

Conclusion
Among CCP+ patients without RA, risk for progression to RA increased substantially with increasing CCP level. This study provides further support for close monitoring for development of RA among CCP+ patients and identifying strategies to mitigate this risk

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Appropriateness of outpatient #antibiotic prescribing among privately insured US patients: ICD-10-CM based cross sectional study

https://www.bmj.com/content/364/bmj.k5092

.. the most common antibiotics were azithromycin (2 931 242, 19.0%), amoxicillin (2 818 939, 18.2%), and amoxicillin-clavulanate (1 784 921, 11.6%). Among these 15 455 834 fills, 1 973 873 (12.8%) were appropriate, 5 487 003 (35.5%) were potentially appropriate, 3 592 183 (23.2%) were inappropriate, and 4 402 775 (28.5%) were not associated with a recent diagnosis code.

Among the 3 592 183 inappropriate fills, 2 541 125 (70.7%) were written in office based settings, 222 804 (6.2%) in urgent care centers, and 168 396 (4.7%) in emergency departments. In 2016, 2 697 918 (14.1%) of the 19 203 264 enrollees filled at least one inappropriate antibiotic prescription, including 490 475 out of 4 631 320 children (10.6%) and 2 207 173 out of 14 571 944 adults (15.2%)...

23% of prescriptions were classified as inappropriate, usually for acute bronchitis, acute upper respiratory tract infection, or respiratory symptoms.

36% were potentially appropriate, most frequently for acute sinusitis, acute suppurative otitis media, or acute pharyngitis.

13% were considered appropriate, most often for urinary tract infections, streptococcal pharyngitis or tonsillitis, and bacterial pneumonia.

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Physical #activity, common #brain pathologies, and cognition in community-dwelling older adults

http://n.neurology.org/content/early/2019/01/16/WNL.0000000000006954

Higher levels of total daily activity (estimate 0.148, 95% confidence interval 0.053–0.0.244, SE 0.049, p = 0.003) and better motor abilities (estimate 0.283, 95% confidence interval, 0.175–0.390, SE 0.055, p < 0.001) were independently associated with better cognition. These independent associations remained significant when terms for AD and other pathologies were added as well as in sensitivity analyses excluding cases with poor cognition or dementia. Adding interaction terms, the associations of total daily activity and motor abilities with cognition did not vary in individuals with and without dementia. The associations of AD and other pathologies with cognition did not vary with the levels of total daily activity or motor abilities.

Conclusions Physical activity in older adults may provide cognitive reserve to maintain function independent of the accumulation of diverse brain pathologies. Further studies are needed to identify the molecular mechanisms underlying this potential reserve and to ensure the causal effects of physical activity.

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#Gastroschisis Trends and Ecologic Link to #Opioid Prescription Rates — United States, 2006–2015

https://www.cdc.gov/mmwr/volumes/68/wr/mm6802a2.htm?s_cid=mm6802a2_w

What is already known about this topic?

Gastroschisis prevalence has increased worldwide. A previous U.S. report found that gastroschisis increased during 1995–2012, with the greatest increase among mothers aged <20 years.

What is added by this report?

During 2011–2015, gastroschisis prevalence was 4.5 per 10,000 live births, which was 10% higher than the prevalence during 2006–2010. An ecologic analysis found a higher prevalence of gastroschisis in areas where opioid prescriptions rates were high, supporting epidemiologic data suggesting an association between opioid use during pregnancy and gastroschisis.

What are the implications for public health practice?

Further public health research on gastroschisis is needed to gain insight into etiology, including the possible role of opioid exposure during pregnancy on birth defects.

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Prevalence of #foot #pain across an international consortium of population based cohorts

https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.23829

Despite the potential burden of foot pain, some of the most fundamental epidemiological questions surrounding the foot remain poorly explored. The prevalence of foot pain has proved difficult to compare across existing studies due to variations in case definitions.

Results
The precise definition of foot pain varied between the cohorts. The prevalence of foot pain ranged from 13 to 36% and was lowest within the cohort that used a case definition specific to pain, compared to the four remaining cohorts that included components of pain, aching or stiffness. Foot pain was generally more prevalent in women, the obese and generally increased with age, being much lower in younger participants (20‐44 years).

Conclusion
Foot pain is common and is associated with female sex, older age and obesity. The prevalence of foot pain is likely affected by the case definition used, therefore consideration must be given for future population studies to use consistent measures of data collection.

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Dietary #emulsifiers consumption alters #anxiety-like and social-related behaviors in mice in a sex-dependent manner

https://www.nature.com/articles/s41598-018-36890-3

Dietary emulsifiers carboxylmethylcellulose (CMC) and polysorbate 80 (P80) alter the composition of the intestinal microbiota and induce chronic low-grade inflammation, ultimately leading to metabolic dysregulations in mice. As both gut microbiota and intestinal health can influence social and anxiety-like behaviors, we investigated whether emulsifier consumption would detrimentally influence behavior

Importantly, emulsifier treatment altered anxiety-like behaviors in males and reduced social behavior in females. It also changed expression of neuropeptides implicated in the modulation of feeding as well as social and anxiety-related behaviors

This study reveals that these commonly used food additives may potentially negatively impact anxiety-related and social behaviors and may do so via different mechanisms in males and females

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#Direct-Acting Antiviral Therapy not Associated with Recurrence of #Hepatocellular Carcinoma in a Multicenter North American Cohort Study

https://www.gastrojournal.org/article/S0016-5085(19)30057-5/pdf

There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort.

In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P=.23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but neither achieved statistical significance.

Conclusion
In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.

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The Imperative for #climate Action to Protect #Health

https://www.nejm.org/doi/full/10.1056/NEJMra1807873

The WHO predicts that 250,000 deaths yearly from 2030 to 2050 will be attributable to climate change. Reductions in greenhouse-gas emissions would be expected to have substantial health benefits — for example, reduced air pollution could lead to a lower risk of noncommunicable disease.

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Toxin Enzyme #Immunoassays Detect #Clostridioides difficile Infection with Greater Severity and Higher Recurrence Rates

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciz009/5274659

Few data suggest Clostridioides difficile infections (CDI) detected by toxin enzyme immunoassays (EIA) are more severe and have worse outcomes than those detected by nucleic acid amplification tests (NAAT) only. We compared toxin-positive and NAAT-positive only CDI across geographically-diverse sites

Of 4878 cases, 2160 (44.3%) were toxin-positive and 2718 (55.7%) were NAAT-positive only. More toxin-positive than NAAT-positive only cases were aged ≥65 years (48.2% vs 38.0%; P<0.0001), had ≥3 unformed stool for ≥1 day (43.9% vs 36.6%; P<0.0001), and had white blood cells ≥15,000/µl (31.4% versus 21.4%; P<0.0001). In multivariable analysis, toxin-positivity was associated with recurrence (adjusted odds ratio [aOR]: 1.89, 95% CI: 1.61-2.23), but not with CDI-related complications (aOR: 0.91, 95% CI: 0.67-1.23) or 30-day mortality (aOR: 0.95; 95% CI: 0.73-1.24).

Conclusions
Toxin-positive CDI is more severe, but there were no differences in adjusted CDI-related complication and mortality rates between toxin-positive and NAAT-positive only CDI that were detected by an algorithm that utilized an initial GDH screening test.

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#Cognitive Impact of Cerebral Small #Vessel Disease Changes in Patients With Hypertension

https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.118.12090

Hypertension is one of the principal risk factors for cerebral small vessel disease progression and cognitive impairment.

Considering the progression of cerebral small vessel disease, the prevalence of incident infarcts was 6.1% and that of incident cerebral microbleeds was 5.5%; progression of periventricular WMH was 22% and that of deep WMH was 48%. Patients with marked progression of periventricular WMH showed a significant decrease in global cognition compared with patients without progression (adjusted mean [SE], −0.519 [0.176] versus 0.057 [0.044], respectively; P value=0.004) and a higher risk of incident mild cognitive impairment (OR, 6.184; 95% CI, 1.506–25.370; P value=0.011).

Therefore, our results indicate that hypertensive patients with progression of periventricular WMH have higher odds of cognitive impairment, even in the early stages of cognitive decline.

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#Blood–brain barrier breakdown is an early biomarker of human #cognitive dysfunction

https://www.nature.com/articles/s41591-018-0297-y

Abstract
Vascular contributions to cognitive impairment are increasingly recognized as shown by neuropathological neuroimaging and cerebrospinal fluid biomarker studies. Moreover, small vessel disease of the brain has been estimated to contribute to approximately 50% of all dementias worldwide, including those caused by Alzheimer’s disease (AD)..

Our data show that individuals with early cognitive dysfunction develop brain capillary damage and BBB breakdown in the hippocampus irrespective of Alzheimer’s Aβ and/or tau biomarker changes, suggesting that BBB breakdown is an early biomarker of human cognitive dysfunction independent of Aβ and tau.

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Accelerated Knee #Osteoarthritis is Characterized by Destabilizing #Meniscal Tears and Pre‐Radiographic Structural Disease Burden

https://onlinelibrary.wiley.com/doi/abs/10.1002/art.40826

At 1 year before the index visit, >75% of adults with AKOA had meniscal damage in ≥2 regions (vs typical KOA: OR=3.19, 95%CI=1.70 to 5.97). By the index visit, meniscal damage in >2 regions was ubiquitous in AKOA; including 42% with a destabilizing meniscal tear (typical KOA=14%). These changes corresponded to larger BMLs and greater cartilage loss.

Conclusion
AKOA is characterized by destabilizing meniscal tears in a knee compromised by meniscal damage in >2 regions, large BMLs, and cartilage loss

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Association of #Exercise Preconditioning With Immediate #Cardioprotection

https://jamanetwork.com/journals/jamacardiology/article-abstract/2664268

Preclinical evidence shows that 1 to 3 episodes of exercise per week will provide strong cardioprotection; gradual, modest cardiovascular risk factor modification or physiological artery remodeling cannot fully explain these benefits. This review highlights preclinical evidence that acute exercise-induced cardiac preconditioning has the ability to activate multiple pathways to confer immediate protection against ischemic events, reduce the severity of potentially lethal ischemic myocardiac injury, and act as a physiological first line of defense.

Conclusions and Relevance Independent of the protective benefits of long-term exercise training on risk factors and adaptation of the cardiovascular system, cardiovascular preconditioning may contribute to the immediate cardioprotection of exercise. In practical terms, this means that 1 episode of exercise can create clinically relevant cardioprotection.

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Association of #Aspirin Use for Primary Prevention With #Cardiovascular Events and Bleeding Events

https://jamanetwork.com/journals/jama/article-abstract/2721178

The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk

Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).

Conclusions and Relevance The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding.

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How effective are trained #dogs at alerting their owners to changes in blood #glycaemic levels?: Variations in performance of glycaemia alert dogs

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210092

Dogs varied in their performance, with median sensitivity to out-of-range episodes at 70% (25th percentile = 50, 75th percentile = 95). To hypoglycaemic episodes the median sensitivity was 83% (66–94%) while to hyperglyaemic episodes it was 67% (17–91%). The median positive predictive value (PPV) was 81% (68–94%), i.e. on average 81% of alerts occurred when glucose levels were out of target range. For four dogs, PPV was 100%. Individual characteristics of the dog, the partnership and the household were significantly associated with performance (e.g., whether the dog was previously a pet, when it was trained, whether its partner was an adult or child).

Conclusions
The large sample shows that the individual performance of dogs is variable, but overall their sensitivity and specificity to OOR episodes are better than previous studies suggest. Results show that optimal performance of glycaemic alert dogs depends not only on good initial and ongoing training, but also careful selection of dogs for the conditions in which they will be working