Późny przerzut do wątroby raka rdzeniastego tarczycy z niskim stężeniem kalcytoniny skutecznie wyleczony metodą radioablacji

  A 28-year-old female consulted in 1994 for a left thyroid nodule known for two years with documented progression. Left lobe resection was performed initially followed by total thyroidectomy without lymph node dissection in September 1994. Pathological examination concluded on unilateral 10 × 40 mm medullary thyroid carcinoma (MTC). RET mutation was negative. Basal and pentagastrin-stimulated CT levels had been normal from 1994 to 2008 when her CT level was found to be elevated at 33 ng/L and increased subsequently to 111 ng/L in 2010. In accordance with guidelines, cervical ultrasound was performed repeatedly with negative results. After discussion in a multidisciplinary meeting and with patient’s consent, an F-Dopa PET scan was proposed in disagreement with guidelines. This scan showed unique uptake in liver segment VI, which was confirmed by MRI. CT levels reached to 253 ng/L when she finally accepted treatment. In February 2013 we performed radiofrequency ablation of the lesion, which allowed normalisation of CT levels. This observation highlights the possibility of late recurrence of MTC. We could propose that for MTC patients with low-calcitonin levels-recurrences F-DOPA-PET/CT is a good diagnostic tool to use in case of repeatedly negative US neck studies. (Endokrynol Pol 2016; 67 (3): 326–329)    Chora w wieku 28 lat zgłosiła się do lekarza w 1994 roku z powodu lewostronnego guzka tarczycy wykrytego 2 lata wcześniej, z potwierdzoną progresją. Wykonano resekcję lewego płata tarczycy. Totalną tyreoidektomię wykonano we wrześniu 1994 roku bez usunięcia węzłów chłonnych. W badaniu patomorfologicznych stwierdzono jednostronnego raka rdzeniastego tarczycy (MTC) o wymiarach 10 × 40 mm. Wynik badania w kierunku mutacji RET był ujemny. Stężenia kalcytoniny (CT, calcitonin), podstawowe i po stymulacji pentagastryną, były prawidłowe od 1994 roku. Do 2008 roku, kiedy stwierdzono podwyższone stężenie CT wynoszące 33 ng/l, a następnie jego dalszy wzrost do 111 ng/l w 2010 roku. Zgodnie z zaleceniami powtórnie wykonano badanie USG szyi, w którym nie stwierdzono nieprawidłowości. Po omówieniu przypadku na spotkaniu wielodyscyplinarnego zespołu i uzyskaniu zgody chorej przeprowadzono badanie F-Dopa PET (niezgodnie z zaleceniami), w którym wykazano pojedyncze ognisko wychwytu w segmencie VI wątroby, co zostało potwierdzone w badaniu MRI. Kiedy chora w końcu zaakceptowała leczenie, stężenia CT zwiększyły się do 253 ng/l. W lutym 2013 roku wykonano ablację zmiany prądem o częstotliwości radiowej, co pozwoliło uzyskać normalizację stężeń CT w 2015 r. Ta obserwacja zwraca uwagę na możliwość późnej wznowy. Autorzy sugerują, że u chorych z MTC z ponownie stwierdzonym niskim stężeniem kalcytoniny wybór F-DOPA-PET/CT jako metody diagnostycznej jest dobrym rozwiązaniem w przypadku powtórnych ujemnych wyników USG szyi. (Endokrynol Pol 2016; 67 (3): 326–329)

Automorphisms of graphs of cyclic splittings of free groups

We prove that any isometry of the graph of cyclic splittings of a finitely generated free group $F_N$ of rank $N\ge 3$ is induced by an outer automorphism of $F_N$. The same statement also applies to the graphs of maximally-cyclic splittings, and of very small splittings.Comment: 22 pages, 5 figures. Small modifications. To appear in Geometriae Dedicat

Habitat Segregation among Trophic Morphs of the Cuatro Ciénegas Cichlid (Herichthys minckleyi

Herichthys minckleyi is an endangered, trophically polymorphic cichlid endemic to the Cuatro Ciénegas basin of Coahuila, Mexico. A molariform morph has stout pharyngeal teeth whereas a papilliform morph has numerous fine pharyngeal teeth. Individuals with intermediate pharyngeal dentition also exist, as does yet another morph, called piscivore. Previous studies indicated that morphs utilize different food sources, thus suggesting morph-specific spatial segregation, since food resource availability is spatially heterogeneous. We present data from an observational study of all morphs (but focusing on the three most common, normal-bodied ones molariform, papilliform and intermediate) in a single spring pool, Poza Mojarral Oeste. We analyzed morph distribution in relation to habitat types, and document morph-specific differences in feeding behavior. Spatio-temporal habitat partitioning was also investigated. Habitat use by molariform, papilliform, and intermediate morphs was found to be non-random. Morphs differed in habitat use, albeit with considerable overlap. Strong segregation among morphs was not detected in any season or time of day, but habitat use patterns varied seasonally within each morph and were consistently different among morphs. All morphs behave basically as feeding generalists. This endangered species may prove more difficult to manage than other, non-polymorphic species. It is clearly important to manage not only for the maintenance of the species, but also for maintenance of its different morphs, which our study indicates may each require different mixes of habitat types. We thus hypothesize that any changes in habitat heterogeneity will lead to altered proportions of the different morphs of the species

Host investment into symbiosis varies among genotypes of the legume Acmispon strigosus, but host sanctions are uniform.

Efficient host control predicts the extirpation of ineffective symbionts, but they are nonetheless widespread in nature. We tested three hypotheses for the maintenance of symbiotic variation in rhizobia that associate with a native legume: partner mismatch between host and symbiont, such that symbiont effectiveness varies with host genotype; resource satiation, whereby extrinsic sources of nutrients relax host control; and variation in host control among host genotypes. We inoculated Acmispon strigosus from six populations with three Bradyrhizobium strains that vary in symbiotic effectiveness on sympatric hosts. We measured proxies of host and symbiont fitness in single- and co-inoculations under fertilization treatments of zero added nitrogen (N) and near-growth-saturating N. We examined two components of host control: 'host investment' into nodule size during single- and co-inoculations, and 'host sanctions' against less effective strains during co-inoculations. The Bradyrhizobium strains displayed conserved growth effects on hosts, and host control did not decline under experimental fertilization. Host sanctions were robust in all hosts, but host lines from different populations varied significantly in measures of host investment in both single- and co-inoculation experiments. Variation in host investment could promote variation in symbiotic effectiveness and prevent the extinction of ineffective Bradyrhizobium from natural populations

Recurrent mutualism breakdown events in a legume rhizobia metapopulation.

Bacterial mutualists generate major fitness benefits for eukaryotes, reshaping the host phenotype and its interactions with the environment. Yet, microbial mutualist populations are predicted to generate mutants that defect from providing costly services to hosts while maintaining the capacity to exploit host resources. Here, we examined the mutualist service of symbiotic nitrogen fixation in a metapopulation of root-nodulating Bradyrhizobium spp. that associate with the native legume Acmispon strigosus. We quantified mutualism traits of 85 Bradyrhizobium isolates gathered from a 700 km transect in California spanning 10 sampled A. strigosus populations. We clonally inoculated each Bradyrhizobium isolate onto A. strigosus hosts and quantified nodulation capacity and net effects of infection, including host growth and isotopic nitrogen concentration. Six Bradyrhizobium isolates from five populations were categorized as ineffective because they formed nodules but did not enhance host growth via nitrogen fixation. Six additional isolates from three populations failed to form root nodules. Phylogenetic reconstruction inferred two types of mutualism breakdown, including three to four independent losses of effectiveness and five losses of nodulation capacity on A. strigosus. The evolutionary and genomic drivers of these mutualism breakdown events remain poorly understood

A Large Polysaccharide Produced by <i>Helicobacter hepaticus</i> Induces an Anti-inflammatory Gene Signature in Macrophages

Interactions between the host and its microbiota are of mutual benefit and promote health. Complex molecular pathways underlie this dialog, but the identity of microbe-derived molecules that mediate the mutualistic state remains elusive. Helicobacter hepaticus is a member of the mouse intestinal microbiota that is tolerated by the host. In the absence of an intact IL-10 signaling, H. hepaticus induces an IL-23-driven inflammatory response in the intestine. Here we investigate the interactions between H. hepaticus and host immune cells that may promote mutualism, and the microbe-derived molecule(s) involved. Our results show that H. hepaticus triggers early IL-10 induction in intestinal macrophages and produces a large soluble polysaccharide that activates a specific MSK/CREB-dependent anti-inflammatory and repair gene signature via the receptor TLR2. These data identify a host-bacterial interaction that promotes mutualistic mechanisms at the intestinal interface. Further understanding of this pathway may provide novel prevention and treatment strategies for inflammatory bowel disease.We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics for the generation of the Sequencing data. F.F. was supported by Cancer Research UK (OCRC-DPhil13-FF) and N.E.I. by the Kennedy Trust (KENN 15 16 03). M.M.-L. received a fellowship from the Spanish Ministry of Education, Culture, and Sport. This work was funded by the Wellcome Trust UK (095688/Z/11/Z), an ERC grant (Advanced Grant Ares(2013)3687660), and the Fondation Louis JeantetS

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Optical Coherence Tomography Angiography to Distinguish Changes of Choroidal Neovascularization after Anti-VEGF Therapy: Monthly Loading Dose versus Pro Re Nata Regimen

Purpose. To compare the qualitative and quantitative choroidal neovascularization (CNV) changes after antivascular endothelial growth factor (anti-VEGF) therapy in treatment-naïve and treated eyes with age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). Methods. Consecutive patients with neovascular AMD underwent multimodal imaging, including OCTA (AngioPlex, CIRRUS HD-OCT model 5000; Carl Zeiss Meditec, Inc., Dublin, OH) at baseline and at three monthly follow-up visits. Treatment-naive AMD patients undergoing anti-VEGF loading phase were included in group A, while treated patients were included in group B. Qualitative and quantitative OCTA analyses were performed on outer retina to choriocapillaris (ORCC) slab. CNV size was measured using a free image analysis software (ImageJ, open-source imaging processing software, 2.0.0). Results. Twenty-five eyes of 25 patients were enrolled in our study (mean age 78.32 ± 6.8 years): 13 treatment-naïve eyes in group A and 12 treated eyes in group B. While qualitative analysis revealed no significant differences from baseline to follow-up in the two groups, quantitative analysis showed in group A a significant decrease in lesion area (P=0.023); in group B, no significant change in the lesion area was observed during anti-VEGF therapy (P=0.93). Conclusion. Treatment-naïve and treated eyes with CNV secondary to neovascular AMD respond differently to anti-VEGF therapy. This should be taken into account when using OCTA for CNV follow-up or planning therapeutic strategies