Search

Background Local injection of adipose tissue-derived mesenchymal stem cells [MSCs] is effective in fistulizing perianal Crohn’s disease [CD]. Less is known about bone marrow-derived MSCs and little is known about predictive factors of response and magnetic resonance imaging [MRI] evolution of the fistulae after MSC injection. Our aims were to evaluate the safety and clinical outcome of bone marrow-derived MSC injection for perianal fistulizing CD, to evaluate the MRI evolution of the fistulae and to identify factors associated with fistula closure. Patients and methods All CD patients with perianal fistula and appropriate drainage with a seton without abscess at MRI were eligible. Clinical examination, biomarkers and pelvic MRI were performed at weeks 0, 12 and 48. The clinical outcome was assessed by closure of the treated external openings at clinical examination and MRI exploration. Results Sixteen patients with a median age of 49 years and a median duration of perianal CD of 8 months were included. No unexpected safety event occurred. At weeks 12 and 48, 9/16 and 8/16 patients had complete fistula[e] closure, respectively, whereas 11/16 patients had at least partial closure. At MRI, the degree of fibrosis increased significantly after MSC injection. In total, 86% of patients with >80% of fibrosis of the fistula tract at week 48 had fistula closure. Fistula closure at week 12 was predictive of fistula closure at week 48. The MAGNIFI-CD did not change significantly over time. Conclusion Open-label injection of bone marrow-derived MSCs was safe and was effective in half of the patients in fistulizing perianal CD and induced significant MRI changes associated with favourable clinical outcome.

We investigate the impact of clouds on the atmosphere of GJ~1214b using the radiatively-coupled, phase-equilibrium cloud model {\sc EddySed} coupled to the {\sc Unified Model} general circulation model. We find that, consistent with previous investigations, high metallicity ($100\times$ solar) and clouds with large vertical extents (a sedimentation factor of $f_\mathrm{sed} = 0.1$) are required to best match the observations, although metallicities even higher than those investigated here may be required to improve agreement further. We additionally find that in our case which best matches the observations ($f_\mathrm{sed}=0.1$), the velocity structures change relative to the clear sky case with the formation of a superrotating jet being suppressed, although further investigation is required to understand the cause of the suppression. The increase in cloud extent with $f_\mathrm{sed}$ results in a cooler planet due to a higher albedo, causing the atmosphere to contract. This also results in a reduced day-night contrast seen in the phase curves, although the introduction of cloud still results in a reduction of the phase offset. We additionally investigate the impact the the {\sc Unified Model}'s pseudo-spherical irradiation scheme on the calculation of heating rates, finding that the introduction of nightside shortwave heating results in slower mid-latitude jets compared to the plane parallel irradiation scheme used in previous works. We also consider the impact of a gamma distribution, as opposed to a log-normal distribution, for the distribution of cloud particle radii and find the impact to be relatively minor., Accepted to MNRAS

Supplementary Figure 2 from Lack of Evidence for Green Tea Polyphenols as DNA Methylation Inhibitors in Murine Prostate

Supplementary Figure 3 from Lack of Evidence for Green Tea Polyphenols as DNA Methylation Inhibitors in Murine Prostate

Supplementary Table 1 from Lack of Evidence for Green Tea Polyphenols as DNA Methylation Inhibitors in Murine Prostate

Supplementary Figure 1 from Lack of Evidence for Green Tea Polyphenols as DNA Methylation Inhibitors in Murine Prostate

Correlation between GRM1 and PSA in hormone-sensitive and castration-resistant LuCaP 35 xenograft model.

Supplementary Figure Legends

Purpose:We recently demonstrated that glutamate receptor GRM1 was expressed at high levels in castration-resistant prostate cancer (CR-PCa) tissues and cells. Herein, we determined the relationship between GRM1 and AR, PSA, and tumor growth, remission, and recurrence in preclinical PCa models. The effect of alterations in GRM1 expression was also investigated on PCa cell growth, migration and invasion. Experimental Design:We used quantitative gene expression and immunohistochemistry to define the temporal association between GRM1 expression and AR, PSA, and tumor growth during CR progression in CWR22 (n = 59) and LuCaP 35 (n = 12) PCa xenografts. The effect of alterations in GRM1 expression levels on growth, migration, and invasion was investigated in GRM1-overexpressed or -silenced PCa cell lines. The effect of DHT on GRM1 expression was determined in the presence or absence of the antiandrogen bicalutamide. Results:We found that GRM1 transcript and tissue expression directly correlated with growth and AR and PSA expression in hormone-sensitive (HS), castrated, and CR tumor xenografts. GRM1 overexpression or silencing directly correlated with PCa cell proliferation, migration, and invasion. DHT increased GRM1 expression via an AR-dependent manner in HS- and CR-PCa cell lines. Conclusions:This is a first report of GRM1 as an androgen and AR-target gene. GRM1 expression directly correlated with tumor growth, regression, and recurrence and may contribute to CR-progression of PCa in preclinical models. Further studies are needed to define the utility of GRM1 as a druggable target or biomarker for PCa.

Details of antibodies used for immunoblotting and immunostaining in tumor xenografts and cell lines.

Supplementary Materials and Methods

PDF file - 125K, Chemokine receptor expression is variably expressed on human PCa cell lines and on localized and metastatic PCa tissue

WMV file - 3MB, Condensed video of FT7+ PCa cell breaching of vascular endothelium

PDF file - 178K, FT expression generates E-selectin-binding determinants on PCa cell glycoproteins and glycolipids

PDF file - 275K

PDF file - 196K, PCa cells prominently express beta1 and alphaVbeta3 integrins

PDF file - 213K, beta1 and alphaVbeta3 are constitutively active and mediate PCa cell adhesion

WMV file - 2.7MB, Condensed video of empty vector PCa cell breaching of vascular endothelium

PDF file - 137K, Modulating FT expression does not alter PCa cell integrin expression or function

Purpose of Review To summarize and critically review recent literature on the relative cost-effectiveness of hearing augmentation versus stapes surgery for the treatment of otosclerosis. Recent Findings Otosclerosis leads to reduced patient quality of life, which can be ameliorated by either stapes surgery, or hearing aid usage. The success of stapes surgery is high, and the risks of serious postoperative complications are low. Hearing aids don’t have the complications of surgery but are associated with long-term costs. Cost-effectiveness models have shown that stapes surgery is a cost-effective method for treating otosclerosis. Summary Both stapes surgery and hearing aids can improve patient-reported quality of life in otosclerosis. Stapes surgery has larger upfront costs and surgical risks, but hearing aids are associated with longer lifetime costs. Stapes surgery is cost-effective for the treatment of otosclerosis.

A powerful tris(4-bromophenyl)aminium hexachloroantimonate (BAHA) mediated regioselective intermolecular coupling reaction of vindoline with a wide range of substrates that include β-ketoesters, β-diketones, β-ketoaldehydes, β-ketonitriles, β-ketolactones, β-ketolactams, β-cyanoesters, and malononitriles is detailed. The BAHA-promoted intermolecular sp(3)/cp(2) coupling, representing a special class of selective C–H functionalization reactions with direct carbon–carbon bond formation, proceeds with generation of a quaternary center bound to the aryl C15 center of vindoline capable of accommodating of the vinblastine C16’ methyl ester and functionalized for subsequent divergent heterocycle introduction. A comprehensive examination of the reaction scope, optimization of subtle reaction parameters, and key insights into the reaction mechanism are described. Contrary to what might be prevailing expectations, studies suggest the plausible mechanism entails initial single-electron oxidation of the substrate enolate, not vindoline, and subsequent regiospecific addition of the resulting electrophilic radical to vindoline. As such and beyond the new arylation reaction with vindoline, the studies define a host of new, previously unrecognized, applications of BAHA and related triarylaminium radical cations that arises from their ability to generate stabilized electrophilic radicals from β-ketoesters and related substrates under non-reducing and metal-free conditions. Those exemplified herein include mediating stabilized enolate free radical arylation, dimerization, allylation, alkene addition, and α-oxidation reactions.

IntroductionBladder cancer is a heterogenous disease and the emerging knowledge on molecular classification of bladder tumors may impact treatment decisions based on molecular subtype. Pre-clinical models representing each subtype are needed to test novel therapies. Carcinogen-induced bladder cancer models represent heterogeneous, immune-competent, pre-clinical testing options with many features found in the human disease.MethodsInvasive bladder tumors were induced in C57BL/6 mice when continuously exposed to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in the drinking water. Tumors were excised and serially passed by subcutaneous implantation into sex-matched syngeneic C57BL/6 hosts. Eight lines were named BBN-induced Urothelium Roswell Park (BURP) tumor lines. BURP lines were characterized by applying consensus molecular classification to RNA expression, histopathology, and immune profiles by CIBERSORT. Two lines were further characterized for cisplatin response.ResultsEight BURP tumor lines were established with 3 male and 3 female BURP tumor lines, having the basal/squamous (BaSq) molecular phenotype and morphology. BURP-16SR was established from a male mouse and has a stromal-rich (SR) molecular phenotype and a sarcomatoid carcinoma morphology. BURP-19NE was established from a male mouse and has a neuroendocrine (NE)-like molecular phenotype and poorly differentiated morphology. The established BURP tumor lines have unique immune profiles with fewer immune infiltrates compared to their originating BBN-induced tumors. The immune profiles of the BURP tumor lines capture some of the features observed in the molecular classifications of human bladder cancer. BURP-16SR growth was inhibited by cisplatin treatment, while BURP-24BaSq did not respond to cisplatin.DiscussionThe BURP lines represent several molecular classifications, including basal/squamous, stroma-rich, and NE-like. The stroma-rich (BURP-16SR) and NE-like (BURP-19NE) represent unique immunocompetent models that can be used to test novel treatments in these less common bladder cancer subtypes. Six basal/squamous tumor lines were established from both male and female mice. Overall, the BURP tumor lines have less heterogeneity than the carcinogen-induced tumors and can be used to evaluate treatment response without the confounding mixed response often observed in heterogeneous tumors. Additionally, basal/squamous tumor lines were established and maintained in both male and female mice, thereby allowing these tumor lines to be used to compare differential treatment responses between sexes.

BackgroundBladder cancer is a heterogenous disease and the emerging knowledge on molecular classification of bladder tumors could have impact to drive treatment decisions based on molecular subtype. Pre-clinical models representing each subtype are needed to test novel therapies. Carcinogen-induced bladder cancer models represent heterogeneous, immune-competent, pre-clinical testing options with many features found in the human disease.MethodsInvasive bladder tumors were induced in C57BL/6 mice when continuously exposed to N-butyl-N-(4-hydroxbutyl nitrosamine) (BBN) in the drinking water. Tumors were excised and serially passed by subcutaneous implantation into sex-matched syngeneic C57BL/6 hosts. Eight tumor lines were developed and named BBN-induced Urothelium Roswell Park (BURP) tumor lines. The BURP lines were characterized by applying consensus molecular classification to RNA expression, histopathology, and immune profiles by CIBERSORT. Two lines were further characterized for cisplatin response.ResultsEight BURP tumor lines were established with 3 male and 3 female BURP tumor lines, having the basal/squamous (BaSq) molecular phenotype and morphology. BURP-16SR was established from a male mouse and has a stromal-rich (SR) molecular phenotype and a sarcomatoid carcinoma morphology. BURP-19NE was established from a male mouse and has a neuroendocrine (NE)-like molecular phenotype and poorly differentiated morphology. The established BURP tumor lines have unique immune profiles with fewer immune infiltrates compared to their originating BBN-induced tumors. The immune profiles of the BURP tumor lines capture some of the features observed in the molecular classifications of human bladder cancer. BURP-16SR growth was inhibited by cisplatin treatment, while BURP-24BaSq did not respond to cisplatin.ConclusionsThe BURP tumor lines represent several molecular classifications, including basal/squamous, stroma-rich, and NE-like. The stroma-rich (BURP-16SR) and NE-like (BURP-19NE) represent unique immunocompetent models that can be used to test novel treatments in these less common bladder cancer subtypes. Six basal/squamous tumor lines were established from both male and female mice. Overall, the BURP tumor lines have less heterogeneity than the carcinogen-induced tumors and can be used to evaluate treatment response without the confounding mixed response often observed in heterogeneous tumors. Additionally, basal/squamous tumor lines were established and maintained in both male and female mice, thereby allowing these tumor lines to be used to compare differential treatment responses between sexes.

Retrosynthetic deconstruction of a core aromatic ring is an especially simplifying retrosynthetic step, reducing the complexity of the precursor synthetic target. Moreover, when implemented to provide a penultimate intermediate, it enables late-stage divergent aryl introductions, permitting deep-seated core aryl modifications ordinarily accessible only by independent synthesis. Herein, we highlight the use of a ketone carbonyl group as the functionality to direct such late-stage divergent aryl introductions onto a penultimate intermediate with a projected application in the total synthesis of vinblastine and its presently inaccessible analogues containing indole replacements. Although the studies highlight this presently unconventional strategy with an especially challenging target in mind, the increase in molecular complexity (intricacy) established by the synthetic implementation of the powerful retrosynthetic disconnection, the use of a ketone as the precursor enabling functionality, and with adoption of either conventional or new wave (hetero)aromatic annulations combine to define a general and powerful strategy suited for widespread implementation with near limitless scope in target diversification.

An approach to the α,β-unsaturated acyl azolium has been developed that exploits N-heterocyclic carbenes (NHCs) and acyl fluorides, without additional oxidants, bases, or preactivated pro-nucleophi...

This is the first genome-wide association study with the Hybrid Mouse Diversity Panel (HDMP) to define the genetic landscape of the variation in the suprathreshold wave 1 amplitude of the auditory brainstem response (ABR) both pre- and post-noise exposure. This measure is correlated with the density of the auditory neurons (AN) and/or the compliment of synaptic ribbons within the inner hair cells of the mouse cochlea. We analyzed suprathreshold ABR for 635 mice from 102 HMDP strains pre- and post-noise exposure (108 dB 10 kHz octave band noise exposure for 2 h) using auditory brainstem response (ABR) wave 1 suprathreshold amplitudes as part of a large survey (Myint et al., Hear Res 332:113–120, 2016). Genome-wide significance levels for pre- and post-exposure wave 1 amplitude across the HMDP were performed using FaST-LMM. Synaptic ribbon counts (Ctbp2 and mGluR2) were analyzed for the extreme strains within the HMDP. ABR wave 1 amplitude varied across all strains of the HMDP with differences ranging between 2.42 and 3.82-fold pre-exposure and between 2.43 and 7.5-fold post-exposure with several tone burst stimuli (4 kHz, 8 kHz, 12 kHz, 16 kHz, 24 kHz, and 32 kHz). Immunolabeling of paired synaptic ribbons and glutamate receptors of strains with the highest and lowest wave 1 values pre- and post-exposure revealed significant differences in functional synaptic ribbon counts. Genome-wide association analysis identified genome-wide significant threshold associations on chromosome 3 (24 kHz; JAX00105429; p

Resume Introduction Le syndrome de Sezary represente 5 % des lymphomes T cutanes, avec un âge moyen d’apparition de 60 ans. Il se presente classiquement sous la forme d’une erythrodermie, associee a une keratodermie palmoplantaire et des adenopathies, mais peut avoir des presentations cliniques trompeuses. Observation Nous rapportons le cas d’un patient de 27 ans sans antecedent notable, presentant une eruption generalisee evoluant depuis 3 mois, non prurigineuse, erythemato-papuleuse a distribution folliculaire, touchant le tronc, les membres et le visage. Une keratodermie palmoplantaire et des oedemes des extremites etaient associes. La presentation clinique etait evocatrice en premier lieu d’un pytiriasis rubra pilaire. Une hyperlymphocytose sanguine et la presence de cellules de Sezary au frottis sanguin etaient mises en evidence et la recherche de lymphocytes T sanguins KIR3DL2 etait positive. Le diagnostic de syndrome de Sezary stade IVA etait retenu a la suite des resultats de la biopsie cutanee et du TEP-scanner. Une photochimiotherapie extra corporelle etait instauree sans efficacite malgre l’ajout de bexacarotene. Une polychimiotherapie de type « cyclophosphamide, doxorubicine, vincristine, etoposide et prednisone » (CHOEP) permettait d’obtenir une reponse complete de courte duree. Apres l’echec de 2 strategies de rattrapage par « dexamethasone, oxaliplatine et cytarabine haute dose » (DHAOx) associe a du brentuximab vedotin puis par clofarabine et cyclophosphamide, l’evolution etait fatale en 9 mois. Discussion Il s’agit d’une presentation clinique et evolutive atypique de lymphome T cutane chez un patient jeune, soulignant l’agressivite des syndromes de Sezary et les difficultes therapeutiques qui en decoulent. Conclusion Le diagnostic de syndrome de Sezary doit etre evoque devant toute dermatose trainante et atypique quel que soit l’âge. La presence de cellules lymphomateuses clonales sur le frottis sanguin en faveur de cellules de Sezary, l’immunophenotypage lymphocytaire sanguin et medullaire et la relecture de la biopsie cutanee ont permis de retenir le diagnostic de syndrome de Sezary.

Rheological evidence of composition fluctuations in disordered diblock copolymers near the order–disorder transition (ODT) has been documented in the literature over the past three decades, characterized by a failure of time–temperature superposition (tTS) to reduce linear dynamic mechanical spectroscopy (DMS) data in the terminal viscoelastic regime to a temperature-independent form. However, for some materials, most notably poly(styrene-b-isoprene) (PS–PI), no signature of these rheological features has been found. We present small-angle X-ray scattering (SAXS) results on symmetric poly(cyclohexylethylene-b-ethylene) (PCHE–PE) diblock copolymers that confirm the presence of fluctuations in the disordered state and DMS measurements that also show no sign of the features ascribed to composition fluctuations. Assessment of DMS results published on five different diblock copolymer systems leads us to conclude that the effects of composition fluctuations can be masked by highly asymmetric block dynamics, the...

To identify the imaging characteristics associated with better hearing outcomes found in cochleovestibular nerve (CVN) abnormalities treated with hearing aids and/or cochlear implantation (CI).Retrospective review.A retrospective review was undertaken of 69 ears with CVN abnormalities seen on magnetic resonance imaging (MRI) treated at a tertiary referral academic center analyzing the clinical features, imaging characteristics, and hearing data. We searched for associations among the hearing and imaging data, hypothesizing that the imaging data was not a good indicator of hearing function.In univariable analysis of all those who underwent aided testing (hearing aid and CI), health status (P = .016), internal auditory canal (IAC) midpoint diameter (P .001), and number of nerves in the IAC (P .001) were predictors of positive hearing outcome. Modiolar abnormalities, cochlear aperture diameter, cochlear malformations, vestibular malformations, and nerves in the cerebellar cistern did not predict hearing outcome (P = .79, .18, .59, .09, .17, respectively). For patients who received CI, health status (P = .018), IAC midpoint (P = .024), and number of nerves in the IAC (P = .038) were significant. When controlling for health status, IAC midpoint diameter (P .001) and number of nerves in the IAC (P .001) remained significant. In our cohort, one out of the eight ears (13%) with Birman class 0 or 1 exhibited responses to sound compared to nine out of 13 ears (70%) with Birman class 2-4.Current imaging modalities cannot accurately depict the status of the cochleovestibular nerve or predict a child's benefit with a CI. Cochlear implantation should be considered in children with abnormal cochleovestibular nerves.3 Laryngoscope, 132:S1-S15, 2022.

The evolving paradigm of the molecular classification of bladder cancer requires models that represent the classifications with less heterogeneity. Robust transcriptome based molecular classifications are essential to address tumor heterogeneity. Patient derived models (PDMs) are a powerful preclinical tool to study specific tumor compartments. We tested if the consensus molecular subtype analysis was applicable to PDMs and evaluated the tumor compartment each model represents. PDMs derived from surgical specimens were established as xenografts (PDX), organoids (PDO), and spheroids (PDS). The surgical specimens and PDMs were molecularly characterized by RNA sequencing. PDMs that were established in immune deficient mice or in vitro significantly downregulated transcripts related to the immune and stromal compartments compared to the surgical specimens. However, PDMs upregulate a patient-specific bladder cancer cell signal which allowed for analysis of cancer cell pathways independent of the tumor microenvironment. Based on transcriptomic signatures, PDMs are more similar to their surgical specimen than the model type; indicating that the PDMs retained unique features of the tumor from which the PDM was derived. When comparing models, PDX models were the most similar to the surgical specimen, while PDO and PDS models were most similar to each other. When the consensus molecular subtype classification system was applied to both the surgical samples and the three PDMs, good concordance was found between all samples indicating that this system of classification can be applied to PDO and PDS models. PDMs reduce tumor heterogeneity and allow analysis of tumor cells while maintaining the gene expression profile representative of the original tumor.

Objective: Posterior neck masses are a relatively poorly characterized entity. The authors attempt to further characterize the anatomy and pathology of the posterior neck by way of a combined single-institution retrospective chart review and systematic review of the literature. Methods: A single-institution retrospective chart review was undertaken for all patients undergoing excision of a posterior neck mass between January 1, 2012, and January 1, 2017. A systematic review of the Medline, Embase, Web of Science, and Cochrane database was undertaken in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in search of case reports and series describing posterior neck masses. Results: A total of 28 patients who underwent excision of a posterior neck mass were encountered during the retrospective chart review. All pathologies were benign, the most prevalent of which was lipoma (22/28, 79%). A total of 19 articles describing a collective 36 posterior neck masses were encountered during the systematic review. Lipomas were the most common pathology (15/36, 42%). All but one of the masses reported were benign (35/36, 97%). Conclusions: Patients presenting with posterior neck masses can be reassured of a low risk of malignancy. The majority of posterior neck masses can be appropriately evaluated via physical examination and ultrasound.

While the enantioselective Rauhut-Currier reaction is established with bis(enone) substrates, it is yet to be reported with less electrophilic bis(enoate) substrates. By exploiting high-nucleophilicity N-heterocyclic carbenes, it is possible to achieve Rauhut-Currier reactions with these substrates. The reaction is demonstrated with a range of intramolecular reactions (20 examples) and six esterification/RC reaction cascades, which all proceed with high enantioselectivity (most >93:7 er).

The utilization of advance directives in individuals with Parkinson's disease (PD) and atypical parkinsonian disorders (APD) and their caregivers requires further investigation. This study determined the utilization rates of four forms of advance directives: living will, durable power of attorney, durable power of attorney for healthcare, and medical orders in these individuals. We hypothesized that having a neurodegenerative parkinsonian disorder or exposure to these disorders would increase the likelihood of having advance directives.50 PD participants, 49 APD participants, 50 caregivers and 50 non-caregiver controls were surveyed regarding advance directives.The median number of advance directives was 1 in controls, 2 in caregivers and PD participants and 3 in APD participants. Patients with PD were 4.08 times more likely to have durable power of attorney (p 0.001) and 2.08 times more likely to have durable power of attorney for healthcare (p = 0.011) than controls. Patients with APD were 1.66 times more likely to have a living will (p = 0.006), 4.81 times more likely to have a durable power of attorney (p 0.001) and 2.47 times more likely to have a durable power of attorney for healthcare (p = 0.003) than controls. Caregivers were1.58 times more likely to have a living will (p = 0.012) and 2.21 times more likely to have a durable power of attorney for healthcare than controls.Having or being exposed to parkinsonian disorders significantly increases the likelihood of utilizing advance directives. Additionally, exposure to a parkinsonian disorder as a caregiver increases advance directive use.

Patient derived models (PDMs) are a powerful tool to study preclinical responses. However, the benefits of each model have not been compared head-to-head when models are derived from the same surgical specimen. PDMs derived from surgical specimens were established as xenografts (PDX), organoids (PDO), and spheroids (PDS). PDMs were molecularly characterized by RNA sequencing. Differential gene expression was determined between the PDMs and surgical specimens. Surgical specimens had the most differentially expressed genes reflecting loss of immune and stromal compartments in PDMs. PDMs and surgical specimens were clustered using the Euclidian distance analysis to test model fidelity. PDMs upregulated a clear, patient-specific bladder cancer signal. Overall, the molecular profiles of PDXs were the most similar to the matching patient surgical specimen than the PDO and PDS from that patient. The epithelial mesenchymal transition (EMT) gene expression profile is maintained in the PDMs showing the persistence of EMT in both in vivo and in vitro model setting. The consensus molecular subtype was determined in order to compare PDMs to each other and their matching surgical specimen, and only surgical specimens with Basal/Squamous or Luminal Papillary molecular subtype established PDMs. Patient derived models reduce tumor heterogeneity and allow analysis of specific tumor compartments while maintaining the gene expression profile representative of the original tumor.

Resume Introduction La tularemie est une maladie d’inoculation zoonotique, causee par un coccobacille a Gram negatif, Francisella tularensis. Elle a ete decrite pour la premiere fois aux Etats-Unis en 1911. C’est une maladie rare ; l’incidence annuelle rapportee en France entre 2002 et 2012 etait de 0,07 cas pour 100 000 habitants. Sa declaration est obligatoire chez l’homme depuis 2003 en France. Observation Nous rapportons une observation de tularemie survenue dans les suites d’une piqure de tique dans le Nord de la France. Discussion La tularemie est une zoonose rare a rechercher en cas d’adenite de cause inexpliquee. Les modes de presentation clinique sont varies et parfois seuls les signes dermatologiques sont manifestes. La serologie bacterienne permet de confirmer le diagnostic. Une therapie antibiotique adaptee instauree precocement permet une evolution favorable et benigne dans la majorite des cas. Toutefois la bacterie, potentiellement letale, est classee parmi les agents de bioterrorisme.

The spiroketal moiety is an important privileged scaffold that occurs extensively in natural products, drugs, and bioactive molecules. Naturally occurring spiroketals are numerous, however aryl-fused spiroketals are relatively rare. The only comprehensive review disclosing the isolation, biological activity, and synthesis of benzannulated spiroketal natural products was published nearly a decade ago. This review will serve as an update of the 2009 review and include all known families of benzannulated spiroketals, detailing their isolation and biological activity where relevant. Although not exhaustive, endeavours towards their total synthesis will be discussed.

Lateral lumbar interbody fusion (LLIF) is an interbody fusion technique which approaches the spine via the transpsoas route. Although such an approach eliminates many of the known complications associated with traditional fusion, it does not allow for the harvesting of local bone. Therefore, alternative strategies must be employed in order to ensure high rates of successful arthrodesis. One such strategy is to increase the volume of bone graft material (BGM) within the cage, thereby improving the environment for osteogenesis and subsequent fusion. In this study, we tested the hypothesis that the use of a novel bone graft delivery system would lead to significantly higher volumes of intra-cage BGM, compared to traditional cage filling methodology. The senior author performed a LLIF on a cadaveric spine in a traditional manner, which included hand-packing the cages with BGM and then inserting them into prepared disc spaces. A CT scan was performed and all BGM cage volumes were calculated. Next, attempts were made to inject additional quantities of BGM into the in situ cages, via the delivery system. A second CT was performed and new cage volumes of BGM were calculated. Results demonstrated significantly higher cage volumes of BGM after the use of the bone graft delivery system (p = 0.014), compared to those volumes achieved with standard cage packing methodology. This first-of-its-kind study suggests the use of a novel bone graft delivery system will significantly increase cage volumes of BGM which potentially may lead to increase rates of arthrodesis and improved clinical outcomes. Keywords: Lateral lumbar interbody fusion, InFill® V2 Lateral Interbody Fusion Device, Local bone alternatives, Bone graft material volume, Bone graft material, Cadaveric pilot study

Resume Introduction La survenue de granulomes a corps etrangers au niveau facial est classiquement rapportee dans la litterature dans les suites d’injections sous-cutanees a visee esthetique. Nous decrivons pour la premiere fois trois cas de reactions faciales granulomateuses par migration sous-cutanee de microbilles injectees pour embolisation dans le reseau arteriel cervico-facial. Observations Une procedure d’embolisation des arteres faciales par microbilles Embogold® etait realisee chez trois patients dans le cadre d’epistaxis ou d’hemostase tumorale. Dix a 45 jours plus tard apparaissaient des nodules douloureux de l’hemiface homolaterale. Les prelevements histologiques montraient une reaction inflammatoire avec cellules geantes et la presence de microbilles dans le tissu cutane. L’evolution etait favorable spontanement dans un cas et sous colchicine dans un autre ; le troisieme cas etait perdu de vue. Discussion Nous avons observe une destruction inflammatoire des parois des vaisseaux embolises, puis une migration des microbilles dans le tissu sous-cutane facial, entrainant une reaction granulomateuse. La survenue simultanee des trois cas, avec plusieurs operateurs et lots de produits, est etonnante pour un produit employe depuis 10 ans sans incident anterieur. Il n’existait pas de comorbidite commune aux trois cas, et l’etude des lots de produits s’est averee sans particularite. La coloration a l’or colloidal de ces microparticules semble jouer un role pro-inflammatoire important. Conclusion Ces trois cas rares illustrent l’interet d’evoquer une reaction granulomateuse a corps etrangers devant l’apparition de lesions nodulaires de la face dans les suites d’une embolisation arterielle cervico-faciale. La colchicine parait etre une alternative therapeutique interessante.

Orienting students to the library, its resources, and its services is a core function of many academic librarians working in public services roles. Librarians often spend considerable time and effort developing face-to-face or online library orientation activities. Many studies have addressed the effectiveness of library orientations on student learning, yet less is known about students' attitudes toward and opinions of these orientations. This study investigated student perceptions and opinions of an online library orientation for agriculture and related disciplines. Our results indicate that students recognize the value of the online library orientation as an important part of their student experience.

Objectives To compare treatment outcomes for sinogenic subdural empyema (SE) between those managed with initial endoscopic sinus surgery (ESS) alone versus those treated with a combination of ESS and craniotomy over the last decade at our institution. To better characterize subdural empyema with regard to presentation, causative pathogens, and treatment course. Methods Retrospective single-center chart review to identify and evaluate pediatric SE patients between 2009 and 2019. Patients meeting inclusion criteria were classified in one of two groups: those who initially underwent ESS or frontal trephination without concurrent neurosurgical procedure and those who underwent craniotomy or burr hole in addition to a sinus procedure. Presenting characteristics and treatment outcomes were compared between the two groups. Results Eighteen patients met inclusion criteria. The ESS alone and the ESS + craniotomy subgroups each had 9 patients with similar baseline characteristics. The ESS + craniotomy group was more likely to present with neurological symptoms (p = 0.039) and have multiple intracranial fluid collections (p = 0.046). 74.1% of patients presented to the Emergency Department (ED) or to their primary medical doctor and were treated with outpatient management prior to hospitalization with definitive surgical management. The most common presenting symptoms were fever, headache and nausea/vomiting. There were no differences between treatment groups in rate of return to the operating room (OR) (p = 1.00), length of stay (LOS) (p = 0.553), or adverse neurological outcomes (p = 0.456). 44.4% of patients in the ESS alone group eventually required neurosurgical intervention. Conclusions Surgical SE patients often present to medical professionals in the primary care setting or ED and are managed with outpatient treatment before admission with definitive treatment. In this small retrospective cohort patients who underwent sinus intervention alone had similar rates of return to OR, LOS and adverse neurological outcomes use as those who underwent a sinus procedure in coordination with a neurosurgical intervention. There may be a group of patients with SE who may be managed with endoscopic procedures alone and further studies should seek to determine the characteristics of this population.

Resume Introduction Les myosites inflammatoires sont un groupe heterogene de maladies musculaires. Elles comprennent les polymyosites, les dermatomyosites (DM), les myosites associees aux cancers, les myosites necrosantes et les myosites a inclusions. Les DM ne comportent parfois que peu ou pas de manifestations musculaires : DM hypo- ou amyopathiques. La dermatomyosite (DM) a anticorps anti-MDA5 est une forme de dermatomyosite rare, souvent amyopathique, dont le pronostic est principalement lie a l’atteinte pulmonaire. Observation Une femme de 69 ans, suivie pour un lymphome gastrique de type mucosa-associated lymphoid tissue (MALT), etait adressee pour une eruption bulleuse. Les investigations realisees permettaient de retenir le diagnostic de pemphigoide bulleuse. Parallelement etait decouverte une dermatomyosite amyopathique avec pneumopathie interstitielle. Une corticotherapie generale etait debutee en association avec le rituximab indique pour son lymphome. L’evolution etait favorable. Discussion La dermatomyosite a anticorps anti-MDA5 doit etre evoquee devant toute atteinte pulmonaire associee a des signes cutanes de dermatomyosite, le plus souvent en l’absence d’atteinte musculaire. Elle representerait jusqu’a 7 % des DM et son pronostic est severe en raison de l’atteinte pulmonaire.

The King-Devick (K-D) test is a 1 to 2 minute, rapid number naming test, often used to assist with detection of concussion, but also has clinical utility in other neurological conditions (eg, Parkinson disease). The K-D involves saccadic eye and other eye movements, and abnormalities thereof may be an early indicator of Alzheimer disease (AD)-associated cognitive impairment. No study has tested the utility of the K-D in AD and we sought to do so. The sample included 206 [135 controls, 39 mild cognitive impairment (MCI), and 32 AD dementia] consecutive subjects from the Boston University Alzheimer's Disease Center registry undergoing their initial annual evaluation between March 2013 and July 2015. The K-D was administered during this period. Areas under the receiver operating characteristic curves generated from logistic regression models revealed the K-D test distinguished controls from subjects with cognitive impairment (MCI and AD dementia) [area under the curve (AUC)=0.72], MCI (AUC=0.71) and AD dementia (AUC=0.74). K-D time scores between 48 and 52 seconds were associated with high sensitivity (>90.0%) and negative predictive values (>85.0%) for each diagnostic group. The K-D correlated strongly with validated attention, processing speed, and visual scanning tests. The K-D test may be a rapid and simple effective screening tool to detect cognitive impairment associated with AD.

Objectives There are significant variations across centers on how to acquire and interpret imaging of children with congenital sensorineural hearing loss and cochleovestibular abnormalities. This study assesses the quality of imaging, sequences included, and accuracy of official radiology reports, to determine if these children are being assessed appropriately. Methods This study is retrospective review of CTs and MRIs from 40 pediatric patients diagnosed with profound sensorineural hearing loss and cochleovestibular structure/nerve abnormalities presenting to a tertiary referral academic center. Images were reviewed by two experienced neuroradiologists and a neurotologist. Findings were compared to official reports, when available. Results Twelve (30%) patients had an MRI only, while 28 (70%) had both an MRI and a CT. There were 3 (10.7%) CTs and 7 (17.5%) MRIs noted to be of poor quality. Children received an average of 6.8 (±2.7) CT acquisitions and 10.9 (±5.7) MRI acquisitions. There was non-concordance between the official report and expert review for 27 (71.1%) ears on CT and 27 (56.3%) ears on MRI. Conclusions These data demonstrate high variability in protocols and quality of medical imaging of children with sensorineural hearing loss. Interpretation of images is highly discordant between official reports and tertiary review. Given these results, we recommend that these children be imaged and evaluated at centers with neuroradiologists who are experienced in interpreting congenital abnormalities of the cochleovestibular system.

Amphibians have been declining around the world for more than four decades. One recognized driver of these declines is the chytrid fungus Batrachochytrium dendrobatidis, which causes the disease chytridiomycosis. Amphibians have complex and varied immune defenses against B. dendrobatidis, but the fungus also has a number of counterdefenses. Previously, we identified two small molecules produced by the fungus that inhibit frog lymphocyte proliferation, methylthioadenosine (MTA) and kynurenine (KYN). Here, we report on the isolation and identification of the polyamine spermidine (SPD) as another significant immunomodulatory molecule produced by B. dendrobatidis. SPD and its precursor, putrescine (PUT), are the major polyamines detected, and SPD is required for growth. The major pathway of biosynthesis is from ornithine through putrescine to spermidine. An alternative pathway from arginine to agmatine to putrescine appears to be absent. SPD is inhibitory at concentrations of ≥10 μM and is found at concentrations between 1 and 10 μM in active fungal supernatants. Although PUT is detected in the fungal supernatants, it is not inhibitory to lymphocytes even at concentrations as high as 100 μM. Two other related polyamines, norspermidine (NSP) and spermine (SPM), also inhibit amphibian lymphocyte proliferation, but a third polyamine, cadaverine (CAD), does not. A suboptimal (noninhibitory) concentration of MTA (10 μM), a by-product of spermidine synthesis, enhances the inhibition of SPD at 1 and 10 μM. We interpret these results to suggest that B. dendrobatidis produces an “armamentarium” of small molecules that, alone or in concert, may help it to evade clearance by the amphibian immune system.