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Microglia and #amyloid precursor protein coordinate control of transient #candida cerebritis with memory deficits

https://www.nature.com/articles/s41467-018-07991-4#ref-CR4

Bloodborne infections with Candida albicans are an increasingly recognized complication of modern medicine. Here, we present a mouse model of low-grade candidemia to determine the effect of disseminated infection on cerebral function and relevant immune determinants.

We show that intravenous injection of 25,000 C. albicans cells causes a highly localized cerebritis marked by the accumulation of activated microglial and astroglial cells around yeast aggregates, forming fungal-induced glial granulomas. Amyloid precursor protein accumulates within the periphery of these granulomas, while cleaved amyloid beta (Aβ) peptides accumulate around the yeast cells..

Mice infected with C. albicans display mild memory impairment that resolves with fungal clearance. Our results warrant additional studies to understand the effect of chronic cerebritis on cognitive and immune function

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Knee #osteoarthritis and #menopausal hormone therapy in postmenopausal women
a nationwide cross-sectional study

https://journals.lww.com/menopausejournal/Abstract/publishahead/Knee_osteoarthritis_and_menopausal_hormone_therapy.97442.aspx

The incidence of osteoarthritis (OA) increases after menopause, and may be related to hormonal changes in women. Estrogen deficiency is known to affect the development of OA, and menopausal hormone therapy (MHT) is suggested to be related to the development of OA. However, the relationship between knee OA and MHT remains controversial. The association between knee OA prevalence and MHT was investigated using large-scale national data.

Results: In the multiple logistic regression models, the OA odds ratio was 0.70 for the MHT group (95% confidence interval 0.50-0.99), compared with the non-MHT group.

Conclusions: The prevalence of knee OA was lower in participants with MHT than in those without MHT

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Draft Recommendation Statement
Hepatitis #B Virus Infection in Pregnant #Women: Screening

https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/hepatitis-b-virus-infection-in-pregnant-women-screening

Importance
Screening for HBV infection during pregnancy identifies women whose infants are at risk of perinatal transmission. Data from a nationally representative sample showed a prevalence of maternal HBV infection of 85.8 cases per 100,000 deliveries from 1998 to 2011 (0.09% of live-born singleton deliveries in the United States).1, 2 Although there are guidelines for universal infant HBV vaccination, rates of maternal HBV have increased annually by 5.5% since 1998.1, 2 Persons infected with HBV during infancy or childhood are more likely to progress to chronic infection. Chronic HBV infection increases long-term morbidity and mortality by predisposing infected persons to cirrhosis of the liver and liver cancer.

USPSTF Assessment
Using a reaffirmation process, the USPSTF concludes with high certainty that the net benefit of screening for HBV infection in pregnant women is substantial.

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Predictors of Clinically Significant #Echocardiography Findings in Older Adults with #Syncope: A Secondary Analysis

https://www.journalofhospitalmedicine.com/jhospmed/article/175074/hospital-medicine/predictors-clinically-significant-echocardiography

Regression analysis identified five predictors of significant findings: (1) history of congestive heart failure, (2) history of coronary artery disease, (3) abnormal electrocardiogram, (4) high-sensitivity troponin-T >14 pg/mL, and 5) N-terminal pro B-type natriuretic peptide >125 pg/mL. These five variables make up the ROMEO (Risk Of Major Echocardiography findings in Older adults with syncope) criteria. The sensitivity of a ROMEO score of zero for excluding significant findings on echocardiography was 99.5% (95% CI: 97.4%-99.9%) with a specificity of 15.4% (95% CI: 13.0%-18.1%).

CONCLUSIONS: If validated, this risk-stratification tool could help clinicians determine which syncope patients are at very low risk of having clinically significant findings on echocardiography.

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Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type #Calcium Channel Antagonists, and Biguanides With Rates of #Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2719703

Drug repurposing is potentially cost-effective, low risk, and necessary in psychiatric drug development. The availability of large, routine data sets provides the opportunity to evaluate the potential for currently used medication to benefit people with serious mental illness (SMI).

To determine whether hydroxylmethyl glutaryl coenzyme A reductase inhibitors (HMG-CoA RIs), L-type calcium channel (LTCC) antagonists, and biguanides are associated with reduced psychiatric hospitalization and self-harm in individuals with SMI.

Conclusions and Relevance This study provides additional evidence that exposure to HMG-CoA RIs, LTCC antagonists, and biguanides might lead to improved outcomes for individuals with SMI. Given the well-known adverse event profiles of these agents, they should be further investigated as repurposed agents for psychiatric symptoms.

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Association of #Statin Therapy With Prevention of Vision-Threatening Diabetic #Retinopathy

https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2720491

Patients in the statin group had a significantly lower rate of diabetic retinopathy nonproliferative diabetic retinopathy (HR, 0.92; 95% CI, 0.86-0.99), proliferative diabetic retinopathy vitreous hemorrhage (HR, 0.62; 95% CI, 0.54-0.71), tractional retinal detachment (HR, 0.61; 95% CI, 0.47-0.79), and macular edema (HR, 0.60; 95% CI, 0.46-0.79) than the nonstatin group, as well as lower rates of interventions such as retinal laser treatment (HR, 0.71; 95% CI, 0.65-0.77), intravitreal injection (HR, 0.74; 95% CI, 0.61-0.89), and vitrectomy (HR, 0.58; 95% CI, 0.48-0.69), along with a smaller number of the interventions (retinal lasers: rate ratio, 0.61; 95% CI, 0.59-0.64; intravitreal injections: rate ratio, 0.68; 95% CI, 0.61-0.76; and vitrectomies: rate ratio, 0.54; 95% CI, 0.46-0.63). Statin therapy was also associated with lower risks of major adverse cardiovascular events (HR, 0.81; 95% CI, 0.77-0.85), new-onset diabetic neuropathy (HR, 0.85; 95% CI, 0.82-0.89), and new-onset diabetic foot ulcers (HR, 0.73; 95% CI, 0.68-0.78).

Conclusions and Relevance Statin therapy was associated with a decreased risk of diabetic retinopathy and need for treatments for vision-threatening diabetic retinopathy in Taiwanese patients with type 2 diabetes and dyslipidemia.

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Changes in #Kidney Function Do Not Differ between Healthy Adults Consuming #Higher- Compared with Lower- or Normal-Protein Diets: A Systematic Review and Meta-Analysis

https://academic.oup.com/jn/article/148/11/1760/5153345

Higher-protein (HP) diets are advocated for several reasons, including mitigation of sarcopenia, but their effects on kidney function are unclear

Methods
We conducted a systematic review and meta-analysis of trials comparing HP (≥1.5 g/kg body weight or ≥20% energy intake or ≥100 g protein/d) with normal- or lower-protein (NLP; ≥5% less energy intake from protein/d compared with HP group) intakes on kidney function.

The post-only comparison showed a trivial effect for GFR to be higher after HP intakes standardized mean difference (SMD): 0.19; 95% CI: 0.07, 0.31; P = 0.002. The change in GFR did not differ between interventions (SMD: 0.11; 95% CI: −0.05, 0.27; P = 0.16). There was a linear relation between protein intake and GFR in the post-only comparison (r = 0.332, P = 0.03), but not between protein intake and the change in GFR (r = 0.184, P = 0.33). The main limitation of the current analysis is the unclear risk of selection bias of the included trials.

Conclusions
Postintervention GFR comparisons indicate that HP diets result in higher GFRs; however, when changes in GFR were compared, dietary protein had no effect. Our analysis indicates that HP intakes do not adversely influence kidney function on GFR in healthy adults.

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#Carbohydrate quality and human #health: a series of systematic reviews and meta-analyses

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31809-9/fulltext

Observational data suggest a 15–30% decrease in all-cause and cardiovascular related mortality, and incidence of coronary heart disease, stroke incidence and mortality, type 2 diabetes, and colorectal cancer when comparing the highest dietary fibre consumers with the lowest consumers

Clinical trials show significantly lower bodyweight, systolic blood pressure, and total cholesterol when comparing higher with lower intakes of dietary fibre. Risk reduction associated with a range of critical outcomes was greatest when daily intake of dietary fibre was between 25 g and 29 g. Dose-response curves suggested that higher intakes of dietary fibre could confer even greater benefit to protect against cardiovascular diseases, type 2 diabetes, and colorectal and breast cancer. Similar findings for whole grain intake were observed.

Findings from prospective studies and clinical trials associated with relatively high intakes of dietary fibre and whole grains were complementary, and striking dose-response evidence indicates that the relationships to several non-communicable diseases could be causal.

Implementation of recommendations to increase dietary fibre intake and to replace refined grains with whole grains is expected to benefit human health. A major strength of the study was the ability to examine key indicators of carbohydrate quality in relation to a range of non-communicable disease outcomes from cohort studies and randomised trials in a single study. Our findings are limited to risk reduction in the population at large rather than those with chronic disease.

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Multicomponent #Frailty Assessment Tools for Older People with #Psychiatric Disorders: A Systematic Review

https://onlinelibrary.wiley.com/doi/abs/10.1111/jgs.15710

Of the 48 multicomponent frailty assessment tools identified, no tool had been developed for, or validated in, older adult populations with a psychiatric disorder. Overall, 20 of 48 frailty assessment tools contained a psychological assessment domain, with 17 of 48 tools citing the presence of depressed mood and/or anxiety as a frailty indicator. Common areas of construct overlap in frailty assessment tools and DSM‐5 diagnostic criteria included weight loss (29 of 48) and fatigue (21 of 48).

Conclusions
Significant construct overlap exists between the indicators of frailty as conceptualized in existing frailty assessment tools and DSM‐5 diagnostic criteria for common psychiatric disorders including major depressive episode and generalized anxiety disorder that has the potential to confound frailty assessment results. Further research is necessary to establish a reliable and valid tool to assess frailty in this population.

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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.