#Metaplastic Cells in the Stomach Arise, Independently of Stem Cells, via Dedifferentiation or Transdifferentiation of #Chief Cells
http://www.gastrojournal.org/article/S0016-5085(17)36690-8/pdf

Spasmolytic polypeptide-expressing metaplasia (SPEM) develops in patients with chronic atrophic gastritis due to infection with Helicobacter pylori; it might be a precursor to intestinal metaplasia and gastric adenocarcinoma. Lineage tracing experiments of the gastric corpus in mice have not established whether SPEM derives from proliferating stem cells or differentiated, post-mitotic zymogenic chief cells in the gland base. We investigated whether differentiated cells can give rise to SPEM using a non-genetic approach in mice. Mice were given intraperitoneal injections of 5-fluorouracil, which blocked gastric cell proliferation, plus tamoxifen to induce SPEM. Based on analyses of molecular and histological markers, we found SPEM developed even in the absence of cell proliferation. SPEM therefore did not arise from stem cells. In histologic analyses of gastric resection specimens from 10 patients with adenocarcinoma, we found normal zymogenic chief cells that were transitioning into SPEM cells only in gland bases, rather than the proliferative stem cell zone. Our findings indicate that SPEM can arise by direct reprogramming of existing cells—mainly of chief cells

#Screening in the community to reduce #fractures in older women (SCOOP): a randomised controlled trial
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32640-5/fulltext

We did a two-arm randomised controlled trial in women aged 70–85 years to compare a screening programme using the Fracture Risk Assessment Tool (FRAX) with usual management

Treatment was recommended in 898 (14%) of 6233 women. Use of osteoporosis medication was higher at the end of year 1 in the screening group compared with controls (15% vs 4%), with uptake particularly high (78% at 6 months) in the screening high-risk subgroup. Screening did not reduce the primary outcome of incidence of all osteoporosis-related fractures (hazard ratio HR 0·94, 95% CI 0·85–1·03, p=0·178), nor the overall incidence of all clinical fractures (0·94, 0·86–1·03, p=0·183), but screening reduced the incidence of hip fractures (0·72, 0·59–0·89, p=0·002). There was no evidence of differences in mortality, anxiety levels, or quality of life.

Interpretation
Systematic, community-based screening programme of fracture risk in older women in the UK is feasible, and could be effective in reducing hip fractures

Manipulating #beliefs about losing control causes checking #behaviour
http://www.sciencedirect.com/science/article/pii/S221136491730115X

Cognitive theories of obsessive-compulsive disorder (OCD) posit that maladaptive beliefs lead to the development of symptoms. However, psychometric studies have provided mixed evidence regarding whether beliefs about control over thoughts predict OCD symptoms above and beyond other obsessive beliefs. Clinical reports have documented concerns among those diagnosed with OCD regarding a potential loss of control over their thoughts and behaviour, indicating that broadening the scope of beliefs about control by integrating aspects of losing control may better explain their role in OCD. In this study, 133 undergraduate participants underwent a bogus EEG session and received (positive or negative) false feedback about the possibility that they may lose control over their thoughts and behaviour, and completed a task asking them to control the pace of pictures. As hypothesized, participants in the high (versus low) beliefs about losing control condition checked significantly more often which keys they should use to control the pictures, t(106.95) = 2.28, p = .02, d = .44, demonstrating that manipulating beliefs about control can impact checking behaviour when a potential loss of control is emphasized. Also, checking behaviour predicted a lower desire for control, such that compulsions may be seen as opportunities to re-establish disrupted control cognitions.

#Atopic dermatitis and #psoriasis: two different immune diseases or one spectrum?
http://www.sciencedirect.com/science/article/pii/S0952791517301061

Highlights
•Psoriasis and AD are diseases of distinct T-cell ‘polar’ subsets.

•Targeting Th17/IL-17 is an extremely effective treatment for psoriasis.

•Targeting Th2/IL-4 & IL-13 is a highly effective treatment for atopic dermatitis.

•However, specific sub-types of atopic dermatitis blend Th17 and Th2 cytokine axes.

•Optimal treatment of AD across subtypes might require targeting multiple cytokines.

#Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic #stroke: a randomised controlled trial
http://svn.bmj.com/content/early/2017/11/08/svn-2017-000104

348 patients were enrolled: 179 in the GBE group and 169 in the control group. With 18 patients lost to follow-up, the dropout rate was 5.17%. Admission data between two groups were similar, but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores (−2.77±0.21 vs −1.99±0.23, P=0.0116 (30 days); −3.34±0.24 vs −2.48±0.26, P=0.0165 (90 days); −4.00±0.26 vs −2.71±0.26, P=0.0004 (180 days)) compared with controls. The National Institutes of Health Stroke Scale scores at 12 and 30 days, the modified Rankin Scale scores for independent rate at 30, 90 and 180 days, and the Barthel Index scores at 30, 90 and 180 days in the GBE group were significantly improved compared with controls. Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30, 90 and 180 days, Webster’s digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days. No significant differences were seen in the incidence of adverse events or vascular events.

Conclusions We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing the incidence of vascular events

Effect of Different Doses of #Galcanezumab vs Placebo for Episodic #Migraine Prevention
https://jamanetwork.com/journals/jamaneurology/fullarticle/2665408

Of the 936 patients assessed, 410 met entry criteria (aged 18-65 years with 4-14 migraine headache days per month and migraine onset prior to age 50 years) and were randomized to receive placebo or galcanezumab.For the primary end point, galcanezumab, 120 mg, significantly reduced migraine headache days compared with placebo (99.6% posterior probability −4.8 days; 90% BCI, −5.4 to −4.2 days vs 95% superiority threshold Bayesian analysis −3.7 days; 90% BCI, −4.1 to −3.2 days). Adverse events reported by 5% or more of patients in at least 1 galcanezumab dose group and more frequently than placebo included injection-site pain, upper respiratory tract infection, nasopharyngitis, dysmenorrhea, and nausea.

Conclusions and Relevance Monthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies. All dosages were safe and well tolerated for the preventive treatment of episodic migraine

The long-term effects of faecal #microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent #Clostridium difficile infection
http://onlinelibrary.wiley.com/doi/10.1111/apt.14443/abstract

Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection. In short-term the treatment has been shown to be safe, however, there are no large, long-term follow-up studies looking into the potential adverse effects There was no difference in the incidence of severe diseases (inflammatory bowel disease, cancer, autoimmune disease, allergy, neurological diseases) between the patient groups. In addition, weight gain did not differ between treatment groups. The FMT treated patients reported that their bowel habits improved significantly faster, they had less irregular bowel function and less symptoms of upper GI-tract when compared to the patients treated with antibiotics. Significantly more patients in FMT-group reported that their mental health improved after the treatment. The willingness to receive FMT treatment for potential new C. difficile infection was significantly higher in both treatment groups compared to other treatment options.

Conclusion
Our study highlights that FMT is a durable, safe and acceptable treatment option for patients with recurrent C. difficile infection also in long term, and it shows potential benefits over antimicrobial treatment

Risk of posttransplant #hepatocellular carcinoma recurrence is greater in recipients with higher #platelet counts in living donor liver transplantation
http://onlinelibrary.wiley.com/doi/10.1002/lt.24961/abstract

Platelets interact with tumor cells and promote metastasis. The importance of platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear. Thus, we aimed to evaluate the association between preoperative platelet count (PLT) and HCC recurrence after living donor liver transplantation. Of 359 recipients of livers from living donors for HCC, 209 of 240 patients who had preoperative PLT ≤75 × 109/L were matched with 97 of 119 patients who had preoperative PLT >75 × 109/L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75 × 109/L was set based on optimum stratification analysis. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. The median follow-up time was 59 months. Before matching, recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%, and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high platelet group. Recurrence risk was significantly greater in the high platelet group in both univariate (hazard ratio HR = 3.09; 95% confidence interval CI, 1.86-5.14; P < 0.001) and multivariate analyses (HR = 2.10; 95% CI, 1.23-3.60; P =  0.007). In the matched analysis, recurrence risk was also greater in the high platelet group in both univariate (HR = 2.33; 95% CI, 1.36-4.01; P =  0.002) and multivariate analyses (HR = 1.90; 95% CI, 1.02-3.54; P =  0.04). Preoperative PLT had no interaction with the Milan criteria, alpha-fetoprotein level, Edmonson grade, microvascular invasion, or intrahepatic metastasis. Incorporation of preoperative PLT into the Milan criteria significantly improved predictive power. Inflammation-based scores including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the inflammation-based index did not show superiority to preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT appears to be an important host factor affecting HCC recurrence after living donor liver transplantation

Trial of Contralateral Seventh Cervical #Nerve Transfer for #Spastic Arm Paralysis
http://www.nejm.org/doi/full/10.1056/NEJMoa1615208

Spastic limb paralysis due to injury to a cerebral hemisphere can cause long-term disability. We investigated the effect of grafting the contralateral C7 nerve from the nonparalyzed side to the paralyzed side in patients with spastic arm paralysis due to chronic cerebral injury

The mean increase in Fugl–Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft.

CONCLUSIONS
In this single-center trial involving patients who had had unilateral arm paralysis due to chronic cerebral injury for more than 5 years, transfer of the C7 nerve from the nonparalyzed side to the side of the arm that was paralyzed was associated with a greater improvement in function and reduction of spasticity than rehabilitation alone over a period of 12 months. Physiological connectivity developed between the ipsilateral cerebral hemisphere and the paralyzed hand

Effectiveness of #ravidasvir plus #sofosbuvir in interferon-naïve and treated patients with chronic hepatitis #C genotype-4
http://www.journal-of-hepatology.eu/article/S0168-8278(17)32286-9/fulltext

•Ravidasvir is a new NS5A inhibitor for HCV.
•Sofosbuvir + Ravidasvir with or without RBV has achieved very high SVR rates.
•Results are comparable for both patients with and without cirrhosis.
•Serious adverse events were noticed in very few treated patients.

A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated.

Conclusions
Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments

#Erectile dysfunction in the trajectory of #cardiovascular disease
http://journals.sagepub.com/doi/full/10.1177/1358863X17744038 .

The study findings advance our knowledge regarding the connection between ED and vascular dysfunction. The association of ED with endothelial dysfunction and early atherosclerosis provides evidence that ED may serve as a marker of early vascular disease that is easily ascertained by clinical history taking. The connection may reflect shared underlying mechanisms leading to ED and CVD. Similar pathophysiology contributes to both endothelial dysfunction and ED, including loss of nitric oxide bioavailability and increased inflammatory activation

The present study emphasizes the relevance of ED to understanding the trajectory of CVD. A simple standardized ED screening may identify early vascular dysfunction. Similarly, vascular dysfunction may serve as a surrogate marker to evaluate the efficacy of cardiovascular targeted therapies in men with ED. The presence of ED portends a higher risk of future cardiovascular events, particularly in intermediate risk men, and may serve as an opportunity for intensification of cardiovascular risk prevention strategies.2 The findings add to the growing evidence supporting additional trials to determine the clinical impact of ED screening and the appropriate cardiovascular-directed evaluation and treatment of men with ED

Potential effect modifiers of the association between physical #activity patterns and #joint symptoms in middle aged women
http://onlinelibrary.wiley.com/doi/10.1002/acr.23430/abstract

To examine whether body mass index (BMI), menopausal status and hormone therapy (HT) use modify the association between physical activity (PA) patterns throughout middle age and incidence and prevalence of joint symptoms in later middle age in women

The groups representing ‘fluctuating’ (odds ratio [OR]=1.34, 99% confidence interval [CI]=1.04-1.72) and ‘none-or-low’ physical activity (OR=1.60, CI =1.08-2.35) had higher odds of incident joint symptoms than those ‘meeting guidelines-at-all-times’. Stratification by BMI showed that this association was statistically significant in the obese group only. No evidence was found for effect modification by menopausal status or HT use. The findings were similar for prevalent joint symptoms.

Conclusions
Maintaining at least low levels of physical activity throughout middle age was associated with lower prevalence and incidence of joint symptoms in later life. This apparent protective effect of physical activity on joint symptoms was stronger in obese women than in under or normal weight women, and not related to menopause and HT status

Comparative effect of #statins on the risk of incident #Alzheimer disease
http://n.neurology.org/content/early/2017/12/15/WNL.0000000000004818

Over the 18-year study period, we identified 465,085 statin users, including 7,669 patients who developed AD during 2,891,268 person-years of follow-up (incidence rate 2.65 95% CI 2.59–2.71 per 1,000 person-years). Compared to synthetic, fungus-derived statins were associated with an increased risk of AD (HR 1.09, 95% CI 1.03–1.15). Lipophilic statins also were associated with higher AD risk (HR 1.18, 95% CI 1.09–1.27) compared to hydrophilic statins, while statin potency did not modify the risk of AD (adjusted HR 1.03, 95% CI 0.98–1.08). The risk was further reduced in sensitivity analyses.

Conclusion Fungus-derived and lipophilic statins were not associated with decreased incidence of AD compared to synthetic and hydrophilic statins. The modest variations in the risk of incident AD observed between statin characteristics needs to be evaluated in future studies on their possible heterogeneous neuroprotective effect

Association of Gastroesophageal #Reflux With #Malignancy of the Upper Aerodigestive Tract in Elderly Patients
https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/2666578?redirect=true

A total of 13 805 patients (median range age, 74 66-99 years; 3418 women 24.76% and 10 387 men 75.24%) with malignancy of the UADT were compared with 13 805 patients without disease and were matched for sex, age group, and year of diagnosis. GERD was associated with a greater odds of developing malignancy of the larynx (adjusted odds ratio aOR, 2.86; 95% CI, 2.65-3.09), hypopharynx (aOR, 2.54; 95% CI 1.97-3.29), oropharynx (aOR, 2.47; 95% CI, 1.90-3.23), tonsil (aOR, 2.14; 95% CI, 1.82-2.53), nasopharynx (aOR, 2.04; 95% CI, 1.56-2.66), and paranasal sinuses (aOR, 1.40; 95% CI, 1.15-1.70).

Conclusions and Relevance GERD is associated with the presence of malignancy of the UADT in the US elderly population. This epidemiological association requires further examination to determine causality and diagnostic utility

Long-Acting Beta agonists (LABAs) and Inhaled Corticosteroids (ICS): Drug Safety Communication - Boxed #Warning About #Asthma-Related Death Removed
https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm590001.htm

FDA's most prominent warning, the Boxed Warning, about asthma-related death has been removed from the drug labels of medicines that contain both an ICS and LABA. A FDA review of four large clinical safety trials shows that treating asthma with long-acting beta agonists (LABAs) in combination with inhaled corticosteroids (ICS) does not result in significantly more serious asthma-related side effects than treatment with ICS alone. A description of the four trials is now also included in the Warnings and Precautions section of the drug labels. These trials showed that LABAs, when used with ICS, did not significantly increase the risk of asthma-related hospitalizations, the need to insert a breathing tube known as intubation, or asthma-related deaths, compared to ICS alone.

The mediating role of sleep in the #fish consumption – #cognitive functioning relationship: a cohort study
https://www.nature.com/articles/s41598-017-17520-w

Greater fish consumption is associated with improved cognition among children, but the mediating pathways have not been well delineated. Improved sleep could be a candidate mediator of the fish-cognition relationship. This study assesses whether 1) more frequent fish consumption is associated with less sleep disturbances and higher IQ scores in schoolchildren, 2) such relationships are not accounted for by social and economic confounds, and 3) sleep quality mediates the fish-IQ relationship. In this cohort study of 541 Chinese schoolchildren, fish consumption and sleep quality were assessed at age 9–11 years, while IQ was assessed at age 12. Frequent fish consumption was related to both fewer sleep problems and higher IQ scores. A dose-response relationship indicated higher IQ scores in children who always (4.80 points) or sometimes (3.31 points) consumed fish, compared to those who rarely ate fish (all p < 0.05). Sleep quality partially mediated the relationship between fish consumption and verbal, but not performance, IQ. Findings were robust after controlling for multiple sociodemographic covariates. To our knowledge, this is the first study to indicate that frequent fish consumption may help reduce sleep problems (better sleep quality), which may in turn benefit long-term cognitive functioning in children

Dietary #antioxidants and 10-year #lung function decline in adults from the ECRHS survey
http://erj.ersjournals.com/content/50/6/1602286

In 2002, adults from three participating countries of the European Community Respiratory Health Survey (ECRHS) answered a questionnaire and underwent spirometry (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)), which were repeated 10 years later. Dietary intake was estimated at baseline with food frequency questionnaires (FFQ). Associations between annual lung function decline (mL) and diet (tertiles) were examined with multivariable analyses. Simes’ procedure was applied to control for multiple testing.

A total of 680 individuals (baseline mean age 43.8±6.6 years) were included. A per-tertile increase in apple and banana intake was associated with a 3.59 mL·year−1 (95% CI 0.40, 7.68) and 3.69 mL·year−1 (95% CI 0.25, 7.14) slower decline in FEV1 and FVC, respectively. Tomato intake was also associated with a slower decline in FVC (4.5 mL·year−1; 95% CI 1.28, 8.02). Only the association with tomato intake remained statistically significant after the Simes’ procedure was performed. Subgroup analyses showed that apple, banana and tomato intake were all associated with a slower decline in FVC in ex-smokers.

Intake of fruits and tomatoes might delay lung function decline in adults, particularly in ex-smokers.

The Effects of Physical #Exercise and Cognitive Training on #Memory and Neurotrophic Factors
https://www.mitpressjournals.org/doi/abs/10.1162/jocn_a_01164?journalCode=jocn

This study examined the combined effect of physical exercise and cognitive training on memory and neurotrophic factors in healthy, young adults. Ninety-five participants completed 6 weeks of exercise training, combined exercise and cognitive training, or no training (control). Both the exercise and combined training groups improved performance on a high-interference memory task, whereas the control group did not. In contrast, neither training group improved on general recognition performance, suggesting that exercise training selectively increases high-interference memory that may be linked to hippocampal function. Individuals who experienced greater fitness improvements from the exercise training (i.e., high responders to exercise) also had greater increases in the serum neurotrophic factors brain-derived neurotrophic factor and insulin-like growth factor-1. These high responders to exercise also had better high-interference memory performance as a result of the combined exercise and cognitive training compared with exercise alone, suggesting that potential synergistic effects might depend on the availability of neurotrophic factors. These findings are especially important, as memory benefits accrued from a relatively short intervention in high-functioning young adults