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Fungal symbionts of terrestrial plants are among the most widespread and well-studied symbioses, relatively little is known about fungi that are associated with macroalgae. To fill the gap in marine fungal taxonomy, we combined simple culture methods with amplicon sequencing to characterize the fungal communities associated with three brown (Sargassum muticum, Pelvetia canaliculata, and Himanthalia elongata) and two red (Mastocarpus stellatus and Chondrus crispus) macroalgae from one intertidal zone. In addition to characterizing novel fungal diversity, we tested three hypotheses: fungal diversity and community composition vary (i) among species distributed at different tidal heights, (ii) among tissue types (apices, mid-thallus, and stipe), and (iii) among "isomorphic" C. crispus life cycle stages. Almost 70% of our reads were classified as Ascomycota, 29% as Basidiomycota, and 1% that could not be classified to a phylum. Thirty fungal isolates were obtained, 18 of which were also detected with amplicon sequencing. Fungal communities differed by host and tissue type. Interestingly, P. canaliculata, a fucoid at the extreme high intertidal, did not show differences in fungal diversity across the thallus. As found in filamentous algal endophytes, fungal diversity varied among the three life cycle stages in C. crispus. Female gametophytes were also compositionally more dispersed as compared to the fewer variable tetrasporophytes and male gametophytes. We demonstrate the utility of combining relatively simple cultivation and sequencing approaches to characterize and study macroalgal-fungal associations and highlight the need to understand the role of fungi in near-shore marine ecosystems.

Cerebral achromatopsia is an acquired colour perception impairment caused by brain injury. Although we lack precise knowledge about prevalence, acquired colour perception deficits are considered to be rare. While both hemispheres contribute to colour perception, most published cases have had bilateral or right hemisphere lesions. In contrast to congenital colour blindness that affects the discrimination between specific hues, cerebral achromatopsia is often described as affecting perception across all colours. Most of the knowledge on cerebral achromatopsia comes from single case studies or case series of patients with colour perception deficits. Here, we explore colour perception deficits in an unbiased sample of patients with stroke affecting the posterior cerebral artery (N=63). Patients were selected based on lesion location only, and not based on the presence of a given symptom. All patients were tested formally with the Farnsworth D-15 Dichotomous Colour Blindness Test and their performance was compared to matched controls (N=44) using single case statistics. In patients with abnormal performance, a qualitative analysis of the patterns of colour difficulties was performed and lesion lateralization was examined. The study is part of the Back of the Brain project (BoB).27% of the patients in the sample showed significant problems with colour discrimination. Within the lesion subgroups, 44% of patients with bilateral lesions, 34% with left hemisphere lesions and 10% with right hemisphere lesions had significant colour impairments. This suggests that colour perception impairments are more common following left hemisphere lesion than right hemisphere lesion. While some patients only had mild deficits, colour perception impairments were in many cases severe. Many patients had selective deficits only affecting the perception of some hues. The results suggest that colour perception difficulties after a PCA stroke are common, and that they vary in severity and expression. In addition, the results point towards a left hemispheric domination in colour processing, contradicting previous reports.

In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.

Background The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)–positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. Methods In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan–Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients’ outcomes during the period from 5 to 20 years. Results Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1–3), and 34% with four to nine nodes involved (T1N4–9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1–3, and 41% with T2N4–9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively. Conclusions After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.)

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). ω3-Polyunsaturated fatty acids (ω3-PUFAs) show protective effects against various renal injuries. It was recently reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI. Renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of LC3, Beclin-1, and Atg7; lower amounts of p62; and higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more AMPK activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

Non-alcoholic steatohepatitis is a component of a wide spectrum of hepatic diseases that range from steatosis and non-alcoholic fatty liver disease, to cirrhosis and hepatocellular carcinoma. NASH has been identified in a significant amount of morbidly obese patients, and a lot of these patients have been undergoing bariatric surgery for weight loss management, as weight loss is the objective and most effective treatment. NASH by itself is a risk factor for the surgery and screening could be done for these patients, although risk/cost/benefits should be assessed.The desirable improvements in the metabolic components of the disease, as well as the procedure itself diminishes significantly hepatic disease, although there is still concern on increasing fibrosis in the long postoperative term. Surgery is still the best option for these patients, but controlled randomized studies are still needed.

The significant annual burden of disease from cholera remains a preventable global tragedy. An oral cholera vaccine (OCV) emergency stockpile represents a good beginning for improved global cholera management, and modeling studies suggest that realizing the greatest impacts of using OCVs for outbreak response depends on national preparedness. Using the stockpile will create opportunities to gain valuable evidence and experience about the potential role and relative cost-effectiveness of OCVs. It is time to see cholera as a serious and preventable global threat worthy of coordinated attention and management, active global surveillance, and increased human and financial resource investments.