A long and distant journey: a case of rectal cancer with metastasis to the orbit

We present the case of a 33-year-old man with acute onset of eye pain and diplopia as the presenting symptoms of rectal cancer with orbital metastasis. Colorectal cancer with orbital metastasis is exceedingly rare with only 7 cases worldwide despite the prevalence of colorectal cancer. Th e rarity of this presentation may be related to the long path through multiple vascular beds that tumor emboli from the rectum must travel in order to reach the orbit. Keyword

Pancreatic cysts suspected to be branch duct intraductal papillary mucinous neoplasm without concerning features have low risk for development of pancreatic cancer.

BackgroundThe risk of developing pancreatic cancer is uncertain in patients with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD-IPMN) based on the "high-risk stigmata" or "worrisome features" criteria proposed in the 2012 international consensus guidelines ("Fukuoka criteria").MethodsRetrospective case series involving patients referred for endoscopic ultrasound (EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent with BD-IPMN. Rates of pancreatic cancer occurring at any location in the pancreas were compared between groups of patients with one or more Fukuoka criteria ("Highest-Risk Group", HRG) and those without these criteria ("Lowest-Risk Group", LRG).ResultsAfter exclusions, 661 patients comprised the final cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001).ConclusionsThis study supports using Fukuoka criteria to stratify the immediate and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of pancreatic cancer was highest during the first year and occurred exclusively in those with "high-risk stigmata" or "worrisome features" criteria. After the first year all BD-IPMN continued to have a low but persistent cancer risk

Is Large Lepton Mixing Excluded?

The original \bnum -(or $\bar{\nu}_{\tau}$-) energy spectrum from the gravitational collapse of a star has a larger average energy than the spectrum for \bnue since the opacity of \bnue exeeds that of \bnum (or $\nu_{\tau}$). Flavor neutrino conversion, \bnue $\leftrightarrow$ \bnum, induced by lepton mixing results in partial permutation of the original \bnue and \bnum spectra. An upper bound on the permutation factor, $p \leq 0.35$ (99$\%$ CL) is derived using the data from SN1987A and the different models of the neutrino burst. The relation between the permutation factor and the vacuum mixing angle is established, which leads to the upper bound on this angle. The excluded region, $\sin^2 2\theta > 0.7 - 0.9$, covers the regions of large mixing angle solutions of the solar neutrino problem: ``just-so" and, partly, MSW, as well as part of region of $\nu_{e} - \nu_{\mu}$ oscillation space which could be responsible for the atmospheric muon neutrino deficit. These limits are sensitive to the predicted neutrino spectrum and can be strengthened as supernova models improve.Comment: 20 pages, TeX file. For hardcopy with figures contact [email protected]. Institute for Advanced Study number AST 93/1

Akutna oralna toksičnost organofosfornih insekticida i inhibicija kolinesteraza u pilića

Acute toxic effects of three commonly used insecticidal preparations of the organophosphates chlorpyrifos, diazinon, and dichlorvos were examined in mixed breed broiler chicks, and cholinesterase activity in plasma and brain were measured. The acute (24 h) oral median lethal doses (LD50) of chlorpyrifos, diazinon, and dichlorvos were 10.79 mg kg-1, 6.32 mg kg-1, and 6.30 mg kg-1, respectively, as determined by the up-and-down method in chicks. Signs of cholinergic toxicosis in the chicks appeared within two hours after dosing, and they included salivation, lacrimation, gasping, frequent defecation, drooping of wings, tremors, convulsions, and recumbency before death. Halving the oral LD50 of chlorpyrifos (5 mg kg-1), diazinon (3 mg kg-1), and dichlorvos (3 mg kg-1) caused immobility and wing drooping, but not the clinical signs of cholinergic toxicity. However, at full LD50 doses of these insecticides, chicks showed clinical signs of cholinergic toxicity similar to those seen in the LD50 experiments. Two out of six chicks died within two hours after treatment with LD50 doses of chlorpyrifos and dichlorvos, whereas LD50 dosing with diazinon caused death in three out of six chicks. Compared to control values, the insecticides reduced plasma and whole brain cholinesterase activities by 29 % to 84 % and 18 % to 77 %, respectively, depending on the dose. The decrease in plasma cholinesterase correlated well (r = 0.82) with that of the brain. These data suggest that organophosphate insecticides administered orally at LD50 doses induce clinical signs of cholinergic poisoning and concurrently reduce brain and plasma cholinesterase activities in chicks.Ispitano je akutno toksično djelovanje triju često rabljenih organofosfornih insekticida klorpirifosa, diazinona i diklorvosa u brojlera te je izmjerena aktivnost kolinesteraza u njihovoj plazmi i mozgu. Srednja letalna doza LD50 klorpirifosa iznosila je 10,79 mg kg-1, diazinona 6,32 mg kg-1 te diklorvosa 6,30 mg kg-1. Prvi su se znakovi kolinergičkoga sindroma u pilića javili unutar dva sata od oralne primjene, a obuhvaćali su slinjenje, suženje, teško disanje, učestalu defekaciju, obješena krila, drhtavicu, grčenje i nesposobnost stajanja uoči smrti. Oralna primjena polovice srednje letalne doze insekticida klorpirifosa (5 mg kg-1), diazinona (3 mg kg-1) i diklorvosa (3 mg kg-1) dovela je do nepokretnosti i obješenih krila, ali bez kliničkih znakova kolinergičke toksičnosti koji su uočeni kod pokusa radi utvrđivanja srednje letalne doze (LD50). Međutim, doze ovih insekticida koje su odgovarale LD50, dovele su do kliničkih znakova kolinergičke toksičnosti sličnih onima zamijećenim kod utvrđivanja LD50. Dva od šest pilića uginula su unutar dva sata od primjene bilo klorpirifosa bilo diklorvosa u dozama koje su odgovarale LD50, dok je diazinon u odgovarajućoj srednjoj letalnoj dozi uzrokovao smrt triju od šest pilića. U odnosu na kontrolne vrijednosti, insekticidi su doveli do smanjenja aktivnosti kolinesteraze koja je ovisila o dozi, a kretala se od 29 % do 84 % u plazmi te od 18 % do 77 % u mozgu. Pad aktivnosti kolinesteraze u plazmi dobro je korelirao s njezinim padom u mozgu (r=0,82). Ovi podaci upućuju na to da oralna primjena organofosfornih insekticida u dozama koje odgovaraju srednjoj letalnoj dozi dovode do znakova kolinergičkoga trovanja u pilića te do istodobnoga pada aktivnosti kolinesteraza u mozgu i plazmi

Plasma and whole brain cholinesterase activities in three wild bird species in Mosul, IRAQ: In vitro inhibition by insecticides

Plasma and brain cholinesterase activities were determined in three wild bird species to assess their exposure to organophosphate and carbamate insecticides which are used in agriculture and public health. In the present study, we used an electrometric method for measurement of cholinesterase activities in the plasma and whole brain of three indigenous wild birds commonly found in northern Iraq. The birds used were apparently healthy adults of both sexes (8 birds/species, comprising 3–5 from each sex) of quail (Coturnix coturnix), collard dove (Streptopelia decaocto) and rock dove (Columba livia gaddi), which were captured in Mosul, Iraq. The mean respective cholinesterase activities (Δ pH/30 minutes) in the plasma and whole brain of the birds were as follows: quail (0.96 and 0.29), collard dove (0.97and 0.82) and rock dove (1.44 and 1.42). We examined the potential susceptibility of the plasma or whole brain cholinesterases to inhibition by selected insecticides. The technique of in vitro cholinesterase inhibition for 10 minutes by the organophosphate insecticides dichlorvos, malathion and monocrotophos (0.5 and 1.0 µM) and the carbamate insecticide carbaryl (5 and10 µM) in the enzyme reaction mixtures showed significant inhibition of plasma and whole brain cholinesterase activities to various extents. The data further support and add to the reported cholinesterase activities determined electrometrically in wild birds in northern Iraq. The plasma and whole brain cholinesterases of the birds are highly susceptible to inhibition by organophosphate and carbamate insecticides as determined by the described electrometric method, and the results further suggest the usefulness of the method in biomonitoring wild bird cholinesterases

Measurements of the Mass, total Width and Two-Photon Partila Width of the ηc\eta_{c} Meson

Using 13.4 $fb^{-1}$ of data collected with the CLEO detector at the Cornell Electron Storage Ring, we have observed 300 events for the two-photon production of ground-state pseudo-scalar charmonium in the decay $\eta_c$ -> $K_S K^{\mp} \pi^{\pm}$. We have measured the $\eta_c$ mass to be (2980.4 +- 2.3 (stat) +- 0.6 (sys)) MeV and its full width as (27.0 +- 5.8 (stat) +- 1.4 (sys)) MeV. We have determined the two-photon partial width of the $\eta_c$ meson to be (7.6 +- 0.8 (stat) +- 0.4 (sys) +- 2.3 (br)) keV, with the last uncertainty associated with the decay branching fraction.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Confining QCD Strings, Casimir Scaling, and a Euclidean Approach to High-Energy Scattering

We compute the chromo-field distributions of static color-dipoles in the fundamental and adjoint representation of SU(Nc) in the loop-loop correlation model and find Casimir scaling in agreement with recent lattice results. Our model combines perturbative gluon exchange with the non-perturbative stochastic vacuum model which leads to confinement of the color-charges in the dipole via a string of color-fields. We compute the energy stored in the confining string and use low-energy theorems to show consistency with the static quark-antiquark potential. We generalize Meggiolaro's analytic continuation from parton-parton to gauge-invariant dipole-dipole scattering and obtain a Euclidean approach to high-energy scattering that allows us in principle to calculate S-matrix elements directly in lattice simulations of QCD. We apply this approach and compute the S-matrix element for high-energy dipole-dipole scattering with the presented Euclidean loop-loop correlation model. The result confirms the analytic continuation of the gluon field strength correlator used in all earlier applications of the stochastic vacuum model to high-energy scattering.Comment: 65 pages, 13 figures, extended and revised version to be published in Phys. Rev. D (results unchanged, 2 new figures, 1 new table, additional discussions in Sec.2.3 and Sec.5, new appendix on the non-Abelian Stokes theorem, old Appendix A -> Sec.3, several references added

Akutna toksičnost veterinarskih i poljoprivrednih formulacija organofosfata diklorvosa i diazinona u pilića

Formulation components of organophosphate insecticidal preparations might affect their toxic action in animals. The objective of this study was to examine and compare the acute toxicity and cholinesterase inhibition in seven to 14-day-old chicks dosed orally with dichlorvos and diazinon in standard veterinary and agricultural formulations. The acute (24 h) oral median lethal doses (LD50) of the formulations were determined using the up-and-down method. Respective LD50 of dichlorvos of the veterinary and agricultural formulations in chicks were 11.1 mg kg-1 and 6.51 mg kg-1 and those of diazinon 6.4 mg kg-1 and 6.7 mg kg-1. Plasma and brain cholinesterase activities were measured by electrometry after in vivo and in vitro exposure to organophosphates. The chicks showed signs of cholinergic toxicosis within one hour of dosing. Dichlorvos (8 mg kg-1) and diazinon (4 mg kg-1) in the veterinary and agricultural formulation signifi cantly reduced both plasma and brain cholinesterase activities in the chicks. The veterinary formulation of dichlorvos reduced plasma ChE by 60 % and agricultural by 40 % and brain ChE by 93 % and 87 %, respectively. In contrast, ChE inhibition by diazinon in the agricultural formulation of diazinon was stronger than by the veterinary formulation; 72 % vs. 64 % in plasma and 97 % vs. 80 % in the brain, respectively. The highest in vitro inhibitions were observed with dichlorvos in the agricultural formulation (50 %) in the brain samples and with diazinon in the agricultural formulation (52 %) in the plasma samples. While they exist, differences between formulations cannot be taken as a rule and further investigations should inventory the toxicity of standard veterinary and agricultural organophosphate formulations in addition to the known data for pure forms.Sastojci formulacija mogu djelovati na toksičnost organofosfatnih insekticidnih pripravaka u životinja. Cilj je ovog istraživanja bio ispitati i usporediti akutnu inhibiciju kolinesteraza u pilića starih 7 do 14 dana koji su na usta primili organofosfatne insekticide diklorvos i diazinon u odgovarajućim formulacijama za veterinarsku odnosno poljoprivrednu primjenu. Dvadesetčetverosatna akutna letalna doza (LD50) diklorvosa bila je 11,1 mg kg-1 u veterinarskim odnosno 6,51 mg kg-1 u poljoprivrednim formulacijama, a diazinona 6,4 mg kg-1 odnosno 6,7 mg kg-1. Do kolinergičke toksikoze u pilića došlo je jedan sat nakon primjene. Nakon izlaganja organofosfatima in vivo i in vitro izmjerena je aktivnost kolinesteraza u plazmi i mozgu s pomoću elektrometrije. Oralne doze diklorvosa (8 mg kg-1) odnosno diazinona (4 mg kg-1) putem veterinarskih odnosno poljoprivrednih formulacija značajno su smanjile aktivnost kolinesteraza u plazmi i mozgu pilića. In vitro su također oba organofosfata inhibirala aktivnost kolinesteraza, bez obzira na formulaciju. Poljoprivredna formulacija diklorvosa izazvala je najjaču inhibiciju (50 %) u mozgu pilića, dok je poljoprivredna formulacija diazinona najjače inhibirala (52 %) aktivnost u plazmi. Ovo istraživanje pokazuje da različite formulacije organofosfatnih insekticida mogu dovesti do različita otrovanja i različito djelovati na kolinesteraznu aktivnost u mozgu i plazmi

Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation

Background and aims: Very early onset inflammatory bowel disease [VEOIBD] is characterized by intestinal inflammation affecting infants and children less than 6 years of age. To date, over 60 monogenic aetiologies of VEOIBD have been identified, many characterized by highly penetrant recessive or dominant variants in underlying immune and/or epithelial pathways. We sought to identify the genetic cause of VEOIBD in a subset of patients with a unique clinical presentation. Methods: Whole exome sequencing was performed on five families with ten patients who presented with a similar constellation of symptoms including medically refractory infantile-onset IBD, bilateral sensorineural hearing loss and, in the majority, recurrent infections. Genetic aetiologies of VEOIBD were assessed and Sanger sequencing was performed to confirm novel genetic findings. Western analysis on peripheral blood mononuclear cells and functional studies with epithelial cell lines were employed. Results: In each of the ten patients, we identified damaging heterozygous or biallelic variants in the Syntaxin-Binding Protein 3 gene [STXBP3], a protein known to regulate intracellular vesicular trafficking in the syntaxin-binding protein family of molecules, but not associated to date with either VEOIBD or sensorineural hearing loss. These mutations interfere with either intron splicing or protein stability and lead to reduced STXBP3 protein expression. Knock-down of STXBP3 in CaCo2 cells resulted in defects in cell polarity. Conclusion: Overall, we describe a novel genetic syndrome and identify a critical role for STXBP3 in VEOIBD, sensorineural hearing loss and immune dysregulation.info:eu-repo/semantics/publishedVersio

Activation of Host Translational Control Pathways by a Viral Developmental Switch

In response to numerous signals, latent herpesvirus genomes abruptly switch their developmental program, aborting stable host–cell colonization in favor of productive viral replication that ultimately destroys the cell. To achieve a rapid gene expression transition, newly minted capped, polyadenylated viral mRNAs must engage and reprogram the cellular translational apparatus. While transcriptional responses of viral genomes undergoing lytic reactivation have been amply documented, roles for cellular translational control pathways in enabling the latent-lytic switch have not been described. Using PEL-derived B-cells naturally infected with KSHV as a model, we define efficient reactivation conditions and demonstrate that reactivation substantially changes the protein synthesis profile. New polypeptide synthesis correlates with 4E-BP1 translational repressor inactivation, nuclear PABP accumulation, eIF4F assembly, and phosphorylation of the cap-binding protein eIF4E by Mnk1. Significantly, inhibiting Mnk1 reduces accumulation of the critical viral transactivator RTA through a post-transcriptional mechanism, limiting downstream lytic protein production, and impairs reactivation efficiency. Thus, herpesvirus reactivation from latency activates the host cap-dependent translation machinery, illustrating the importance of translational regulation in implementing new developmental instructions that drastically alter cell fate