Three-dimensional modeling in anatomy-Tool or terror?

Three-dimensional (3D) modeling is a recent, innovative approach to teaching anatomy. There is little literature, however, to suggest how 3D modeling is best used to teach students and whether or not students can gain the same level of understanding as they might use more traditional, hands-on, teaching methods. This study evaluated the use of a 3D modeling software in both a flipped classroom curriculum and as an active learning tool in comparison to traditional, physical model-based teaching. Pre- and post-course content-based assessments were used to evaluate students' learning. Our findings indicated no significant difference between standard and flipped classroom learning; however, the students who used 3D modeling software as an active learning tool significantly underperformed students in the standard group (F(2,1060) = 112.43, p < 0.0001). These findings suggest that these technologies may not yet be useful as a primary means of instruction. Possible explanations may include cognitive overload in navigating the system, intrinsic limitations of the software, or other factors. Further development and research of these technologies is necessary prior to their adoption into teaching practices in anatomy.

Shades of digital deception: Self-presentation among men seeking men on locative dating apps.

In recent years, location-based real-time dating apps like Grindr and Tinder have assumed an increasingly pivotal role in brokering socio-sexual relations between men seeking men and have proven to be fertile ground for the study of identity negotiation and impression management. However, current research has given insufficient consideration to how various contextual elements of technology use interact with one another to shape self-presentation behaviour. Through analysis of interview data, we found impression construction on these apps reflects tensions between authentic depiction of the self-concept and self-enhancement via deception. Whether and the extent to which one engages in deception depends on how a number of technological affordances, platform-specific community norms and userbase characteristics interact with each other. Self-presentational choices were a result of a combination of deception facilitators, for example, belief in the normalcy of lying, and constraining determinants, for example, the expectation of brokering physical connection. Impression construction determinants also interact in ways where the influence of any one element is dependent on others. This was most plainly evidenced in the interactions between stigma management concerns, the affordances of audience visibility/control and locatability and common ground reinforcing social hierarchy.

After the blades: The late MIS3 flake-based technology at Shuidonggou Locality 2, North China.

Contrasting with the predominance of blade-based assemblages in the Eurasian Upper Paleolithic, the large-scale persistence of a core-and-flake technology remains one of the defining features of Late Pleistocene lithic technology in East Asia. In North China, Shuidonggou is an exceptional site where both technologies are documented, therefore, it is an important archaeological sequence to understand regional technological evolution during the Marine Isotopic Stage 3. Blade technology first occurred at Shuidonggou Locality 1 and 2 around 41 ka cal BP while core-and-flake assemblages were widespread in North China. However, systematic technological studies on assemblages postdating 34 ka cal BP have not been conducted to examine whether the blade technology appeared and disappeared over a short yet abrupt episode, or persists and integrates into other forms in the region. Here, we conducted qualitative and quantitative analyses to reconstruct lithic productions on the assemblages at Shuidonggou Locality 2, dated after 34 ka cal BP. Our results show that there is a total absence of laminar elements in stone artifacts dated to 34-28 ka cal BP at Shuidonggou. Instead, we observe a dominance of an expedient production of flakes in the younger assemblages, illustrating a rapid return to flake-based technology after a relatively brief episode of stone blade production. Combining archaeological, environmental, and genetic evidence, we suggest that this technological 'reversal' from blades back to core and flake technology reflect population dynamics and adaptive strategies at an ecological interface between East Asian winter and summer monsoon.

Model of severe malaria in young mice suggests unique response of CD4 T cells.

Severe malaria occurs most in young children but is poorly understood due to the absence of a developmentally-equivalent rodent model to study the pathogenesis of the disease. Though functional and quantitative deficiencies in innate response and a biased T helper 1 (Th1) response are reported in newborn pups, there is little information available about this intermediate stage of the adaptive immune system in murine neonates. To fill this gap in knowledge, we have developed a mouse model of severe malaria in young mice using 15-day old mice (pups) infected with Plasmodium chabaudi. We observe similar parasite growth pattern in pups and adults, with a 60% mortality and a decrease in the growth rate of the surviving young mice. Using a battery of behavioral assays, we observed neurological symptoms in pups that do not occur in infected wildtype adults. CD4+ T cells were activated and differentiated to an effector T cell (Teff) phenotype in both adult and pups. However, there were relatively fewer and less terminally differentiated pup CD4+ Teff than adult Teff. Interestingly, despite less activation, the pup Teff expressed higher T-bet than adults' cells. These data suggest that Th1 cells are functional in pups during Plasmodium infection but develop slowly.

On the kinetic mechanism of dimethylarginine dimethylaminohydrolase.

Dimethylarginine dimethylaminohydrolase (DDAH, EC 3.5.3.18) catalyzes the hydrolysis of asymmetric Nω,Nω-dimethyl-l-arginine (ADMA), an endogenous inhibitor of human nitric oxide synthases. The active-site cysteine residue has been proposed to serve as the catalytic nucleophile, forming an S-alkylthiourea reaction intermediate, and serving as a target for covalent inhibitors. Inhibition can lead to ADMA accumulation and downstream inhibition of nitric oxide production. Prior studies have provided experimental evidence for formation of this covalent adduct but have not characterized it kinetically. Here, rapid quench-flow is used with ADMA and the DDAH from Pseudomonas aeruginosa to determine the rate constants for formation (k2 = 17 ± 2 s-1) and decay (k3 = 1.5 ± 0.1 s-1) of the covalent S-alkylthiourea adduct. A minimal kinetic mechanism for DDAH is proposed that supports the kinetic competence of this species as a covalent reaction intermediate and assigns the rate-limiting step in substrate turnover as hydrolysis of this intermediate. This work helps elucidate the different reactivities of S-alkylthiourea intermediates found among the mechanistically diverse pentein superfamily of guanidine-modifying enzymes and provides information useful for inhibitor development.

Ultrasound as a Learning Tool in Bachelor-Level Anatomy Education.

Point of care ultrasound (POCUS) has become an increasingly common diagnostic tool in the clinical environment. As a result, it is being used earlier for medical students in Undergraduate Medical Education (UME) as a learning tool for the basic sciences including gross anatomy. There is little literature, however, to support its utility for basic science education in students currently seeking a bachelor's degree. This study consisted of fourteen currently enrolled bachelor students with previous instruction in human anatomy and physiology. Students participated in an ultrasound didactic and an interactive ultrasound experience with volunteers. Before and after this session, students were asked to complete an assessment measuring their spatial understanding of the human anatomy and their ability to locate structures using ultrasound. Wilcoxon's signed-rank tests comparing assessment scores showed significant improvement on both portions of the assessment. Based on this improvement, we suggest that ultrasound is a valid educational tool which can be used at the bachelor-level to effectively enhance students' learning of anatomy and provide hands on experience with modern technology. Further research with larger samples will be necessary to determine whether it would supplement or replace more traditional teaching modalities.

Building community, one swipe at a time: hook-up apps and the production of intimate publics between women.

Hook-up apps are an increasingly popular way for women to meet other people for sex, dating, relationships, and more. As a mundane and habitual form of media, the multiple uses of hook-up apps allow for the production of intimacy in surprising and complex ways. This paper draws on narrative interviews with 15 self-identifying women to explore how dating and hook-up apps help produce 'intimate publics' for women. The field of intimate publics available to women users of hook-up apps is broader than those afforded by in-app interactions; there is an entire network of intimacy, sociality, and publicity that forms around hook-up apps. Our findings show that while both queer and straight women use hook-up apps to find sex, hook-ups, dates, and relationships, they are also central to building community, friendship, and sociality between women.

Use of a Novel Memory Aid to Educate Perioperative Team Members on Proper Patient Positioning Technique.

Interdisciplinary collaboration is key to safe surgical positioning. Although the surgical procedure dictates the patient's position, surgeons, anesthesia care providers, intraoperative nurses, and ancillary staff members must work together to achieve the goal of safe positioning. Correct patient positioning includes the provision of adequate access to the surgical site for the surgeon and surgical assistants. Surgical positions may put the patient at risk of injury. Understanding human anatomy, including the nerves commonly affected by each surgical position, can help the surgical team prevent accidental and irreversible patient injury. A lack of knowledge of proper positioning practices can result in serious patient injury, such as permanent paralysis, blindness, tissue necrosis, burns, bone fracture, and even death. This article reviews surgical positioning and introduces a learning module that involves the use of mnemonics as memory aids for perioperative team members who are learning proper positioning techniques.

An Ideal C3-Symmetric Sulfate Complex: Molecular Recognition of Oxoanions by m-Nitrophenyl- and Pentafluorophenyl-Functionalized Hexaurea Receptors.

The anion-binding properties of two tripodal-based hexaureas appended with the m-nitrophenyl (1) and pentafluorophenyl (2) groups have been studied both experimentally and theoretically, showing strong affinities for sulfate over other inorganic oxoanions such as hydrogen sulfate, dihydrogen phosphate, bicarbonate, nitrate, and perchlorate. The structural analysis of the sulfate complex with 1 reveals that the receptor organizes all urea-binding sites toward the cavity at precise orientations around a tetrahedral sulfate anion to form an ideal C3-symmetric sulfate complex that is stabilized by 12 hydrogen-bonding interactions. The receptor and the encapsulated sulfate are located on the threefold axis passing through the bridgehead nitrogen of 1 and the sulfur atom of the anionic guest. The high-level density functional theory calculations support the crystallographic results, demonstrating that the C3-symmetric conformation of the sulfate complex is achieved due to the complementary NH···O between the receptor and sulfate.

Benzoxazoles, Phthalazinones, and Arylurea-Based Compounds with IMP Dehydrogenase-Independent Antibacterial Activity against Francisella tularensis.

Francisella tularensis is the causative agent of tularemia and a potential biowarfare agent. The virulence of F. tularensis is decreased by deletion of guaB, the gene encoding IMP dehydrogenase (IMPDH), suggesting that this enzyme is a target for antibacterial design. Here we report that F. tularensis growth is blocked by inhibitors of bacterial IMPDHs. Seventeen compounds from two different frameworks, designated the D and Q series, display antibacterial activities with MICs of <1 µM. These compounds are also active against intracellular infections. Surprisingly, antibacterial activity does not correlate with IMPDH inhibition. In addition, the presence of guanine does not affect the antibacterial activity of most compounds, nor does the deletion of guaB These observations suggest that antibacterial activity derives from inhibition of another target(s). Moreover, D compounds display antibacterial activity only against F. tularensis, suggesting the presence of a unique target or uptake mechanism. A ΔguaB mutant resistant to compound D73 contained a missense mutation (Gly45Cys) in nuoB, which encodes a subunit of bacterial complex I. Overexpression of the nuoB mutant conferred resistance to D73 in both wild-type and ΔguaB strains. This strain was not resistant to Q compounds, suggesting that a different off-target mechanism operates for these compounds. Several Q compounds are also effective against Mycobacterium tuberculosis, in which a second target has also been implicated, in addition to IMPDH. The fortuitous presence of multiple targets with overlapping structure-activity relationships presents an intriguing opportunity for the development of robust antibiotics that may avoid the emergence of resistance.

Remarkable hexafunctional anion receptor with operational urea-based inner cleft and thiourea-based outer cleft: Novel design with high-efficiency for sulfate binding.

The recognition of anions by designed receptors has attracted much attention in recent days. In particular, the selective binding of sulfate with artificial receptors is important because of its relevance to many biological and environmental applications. However, the development of organized molecular receptors with high-efficiency for sulfate binding still remains a significant challenge. We report a novel para-phenylene-bridged hexafunctional tripodal receptor that contains a urea-based inner cleft and a thiourea-based outer cleft, providing perfect sites for step-wise binding of two anions within a single cavity. The new receptor was synthesized in a three-step process, and was investigated for its anion binding properties by 1H NMR titrations, 2D NOESY experiments and computational studies. As indicated by solution binding studies, the receptor selectively binds sulfate over other oxoanions, forming a 1:2 stoichiometric complex that is stabilized via strong H-bonding interactions. High-level DFT calculations reveal that the receptor, owing to the enhanced H-bonding ability of thiourea groups, initially encapsulates one sulfate in its thiourea-based outer cleft, followed by a second encapsulation in its urea-based inner cleft. Such a functionalized receptor with the unique combination of urea-based cleft and thiourea-based cleft in a single receptor has not been reported previously.

Synthetic Receptors Induce Anti Angiogenic and Stress Signaling on Human First Trimester Cytotrophoblast Cells.

The cytotrophoblast (CTB) cells of the human placenta have membrane receptors that bind certain cardiotonic steroids (CTS) found in blood plasma. One of these, marinobufagenin, is a key factor in the etiology of preeclampsia. Herein, we used synthetic receptors (SR) to study their effectiveness on the angiogenic profile of human first trimester CTB cells. The humanextravillous CTB cells (Sw.71) used in this study were derived from first trimester chorionic villus tissue. Culture media of CTB cells treated with ≥1 nM SR level revealed sFlt-1 (Soluble fms-like tyrosine kinase-1) was significantly increased while VEGF (vascular endothelial growth factor) was significantly decreased in the culture media (* p < 0.05 for each) The AT2 receptor (Angiotensin II receptor type 2) expression was significantly upregulated in ≥1 nM SR-treated CTB cells as compared to basal; however, the AT1 (Angiotensin II receptor, type 1) and VEGFR-1 (vascular endothelial growth factor receptor 1) receptor expression was significantly downregulated (* p < 0.05 for each). Our results show that the anti-proliferative and anti-angiogenic effects of SR on CTB cells are similar to the effects of CTS. The observed anti angiogenic activity of SR on CTB cells demonstrates that the functionalized-urea/thiourea molecules may be useful as potent inhibitors to prevent CTS-induced impairment of CTB cells.

Anion Complexation Studies of 3-Nitrophenyl-Substituted Tripodal Thiourea Receptor: A Naked-Eye Detection of Sulfate via Fluoride Displacement Assay.

A thiourea-based tripodal receptor L substituted with 3-nitrophenyl groups has been synthesized, and the binding affinity for a variety of anions has been studied by 1H NMR titrations and nuclear Overhauser enhancement spectroscopy experiments in dimethyl sulfoxide-d6. As investigated by 1H NMR titrations, the receptor binds an anion in a 1:1 binding mode, showing the highest binding and strong selectivity for sulfate anion. A competitive colorimetric assay in the presence of fluoride suggests that the sulfate is capable of displacing the bound fluoride, showing a sharp visible color change. The strong affinity of L for sulfate was further supported by UV-vis titrations and density functional theory (DFT) calculations. Time-dependent DFT calculations indicate that the fluoride complex possesses a different optical absorption spectrum (due to charge transfer between the fluoride and the surrounding ligand) than the sulfate complex, reflecting the observed colorimetric change in these two complexes. The receptor was further tested for its biocompatibility on primary human foreskin fibroblasts and HeLa cells, exhibiting an excellent cell viability up to 100 µM concentration.

Inter-Observer Variability in the Interpretation of Endoscopic Mucosal Resection Specimens of Esophageal Adenocarcinoma: Interpretation of ER specimens.

INTRODUCTION: Endoscopic resection (ER) has revolutionized the staging and therapy of superficial esophageal adenocarcinoma. Pathologic evaluation allows an assessment of the risk of lymph node metastases based on tumor characteristics. The aim of this study was to assess the inter-observer variability in pathologic assessment of ER specimens of esophageal adenocarcinoma. METHODS: We performed a retrospective study on ER specimens of superficial esophageal adenocarcinoma from four US institutions. Original endoscopic resection slides were re-reviewed by two blinded, experienced (study) gastrointestinal pathologists for the depth of tumor invasion, tumor grade, and the presence of lymphovascular invasion (LVI). Discordance was considered present only when both study pathologists disagreed with the original report. RESULTS: There were 25 ER specimens reviewed for this study, and discordance occurred in 12 of the 25 specimens (48%) for the depth of tumor invasion. In most cases (83%), the discordance was related to overstaging a true T1a lesion. We found that only 38% of true T1a lesions were correctly staged for depth of invasion. Less commonly discordance was secondary to understaging a true T1b lesion. There was concordance between the two study pathologists in 22/25 cases (88%) on the depth of invasion. Discordance was present for tumor grade in 8/18 cases (44%) and for LVI in 4/16 cases (25%). Concordance between the study pathologists was 80% for tumor grade and 88% for LVI. CONCLUSIONS: There was an alarmingly high rate of discordance (48%) between the study pathologists and the original pathology assessment for the depth of tumor invasion in ER specimens. This was particularly common for lesions called T1b on the original pathology report. Since critical decisions are made regarding esophageal preservation or esophagectomy on the basis of the pathologic interpretations of ER specimens, it behooves surgeons to understand the inter-observer variability. Review of ER specimens by an experienced GI pathologist is recommended to ensure that patients receive the appropriate treatment for superficial esophageal adenocarcinoma.

The Durability of Endoscopic Therapy for Treatment of Barrett's Metaplasia, Dysplasia, and Mucosal Cancer After Nissen Fundoplication.

INTRODUCTION: Radiofrequency ablation (RFA) ± endoscopic resection (EMR) is an established treatment strategy for neoplastic Barrett's and intramucosal cancer. Most patients are managed with proton pump inhibitors. The incidence of recurrent Barrett's metaplasia, dysplasia, or cancer after complete eradication is up to 43 % using this strategy. We hypothesize the addition of fundoplication should result in a lower recurrence rates after complete eradication. METHODS: Multi-institutional retrospective review of patients undergoing endotherapy followed by Nissen fundoplication RESULTS: A total of 49 patients underwent RFA ± EMR followed by Nissen fundoplication. Complete remission of intestinal metaplasia (CR-IM) was achieved in 26 (53 %) patients, complete remission of dysplasia (CR-D) in 16 (33 %) patients, and 7 (14 %) had persistent neoplastic Barrett's. After fundoplication, 18/26 (70 %) remained in CR-IM. An additional 10/16 CR-D achieved CR-IM and 4/7 with persistent dysplasia achieved CR-IM. One patient progressed to LGD while no patient developed HGD or cancer. CONCLUSION: Endoscopic therapy for Barrett's dysplasia and/or intramucosal cancer followed by fundoplication results in similar durability of CR-IM to patients being managed with PPIs alone after endoscopic therapy. However, fundoplication may be superior in preventing further progression of disease and the development of cancer. Fundoplication is an important strategy to achieve and maintain CR-IM, and facilitate eradication of persistent dysplasia.

Synthesis and anion binding studies of tris(3-aminopropyl)amine-based tripodal urea and thiourea receptors: Proton transfer-induced selectivity for hydrogen sulfate over sulfate.

Tris(3-aminopropyl)amine-based tripodal urea and thiourea receptors, tris([(4-cyanophenyl)amino]propyl)urea (L1) and tris([(4-cyanophenyl)amino]propyl)thiourea (L2), have been synthesized and their anion binding properties have been investigated for halides and oxoanions. As investigated by 1H NMR titrations, each receptor binds an anion with a 1:1 stoichiometry via hydrogen-bonding interactions (NH⋯anion), showing the binding trend in the order of F- > H2PO4- > HCO3- > HSO4- > CH3COO- > SO42- > Cl- > Br- > I in DMSO-d6 . The interactions of the receptors were further studied by 2D NOESY, showing the loss of NOESY contacts of two NH resonances for the complexes of F-, H2PO4-, HCO3-, HSO4- or CH3COO- due to the strong NH⋯anion interactions. The observed higher binding affinity for HSO4- than SO42- is attributed to the proton transfer from HSO4- to the central nitrogen of L1 or L2 which was also supported by the DFT calculations, leading to the secondary acid-base interactions. The thiourea receptor L2 has a general trend to show a higher affinity for an anion as compared to the urea receptor L1 for the corresponding anion in DMSO-d6 . In addition, the compound L2 has been exploited for its extraction properties for fluoride in water using a liquid-liquid extraction technique, and the results indicate that the receptor effectively extracts fluoride from water showing ca. 99% efficiency (based on L2).

"It's complicated": collective memories of transgender, queer, and questioning youth in high school.

Using the qualitative participatory action methodology, collective memory work, this study explored how transgender, queer, and questioning (TQQ) youth make meaning of their sexual orientation and gender identity through high school experiences. Researchers identified three major conceptual but overlapping themes from the data generated in the transgender, queer, and questioning youth focus group: a need for resilience, you should be able to be safe, and this is what action looks like! The researchers discuss how as a research product, a documentary can effectively "capture voices" of participants, making research accessible and attractive to parents, practitioners, policy makers, and participants.

Phthalazinone inhibitors of inosine-5'-monophosphate dehydrogenase from Cryptosporidium parvum.

Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition. This protozoan parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides. A CpIMPDH-selective N-aryl-3,4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign. Herein we report a structure-activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH. In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C. parvum infection is also presented.

Expert training with standardized operative technique helps establish a successful penile prosthetics program for urologic resident education.

INTRODUCTION: The challenge of resident education in urologic surgery programs is to overcome disparity imparted by diverse patient populations, limited training times, and inequalities in the availability of expert surgical educators. Specifically, in the area of prosthetic urology, only a small proportion of programs have full-time faculty available to train residents in this discipline. AIM: To examine whether a new model using yearly training sessions from a recognized expert can establish a successful penile prosthetics program and result in better outcomes, higher case volumes, and willingness to perform more complex surgeries. METHODS: A recognized expert conducted one to two operative training sessions yearly to teach standardized technique for penile prosthetics to residents. Each session consisted of three to four operative cases performed under the direct supervision of the expert. Retrospective data were collected from all penile prosthetic operations before (February, 2000 to June, 2004: N = 44) and after (July, 2004 to October, 2007: N = 79) implementation of these sessions. MAIN OUTCOME MEASURES: Outcomes reviewed included patient age, race, medical comorbidities, operative time, estimated blood loss, type of prosthesis, operative approach, drain usage, length of stay, and complications including revision/explantation rates. Statistical analysis was performed using Student's t-tests, Fisher's tests, and survival curves using the Kaplan-Meier technique (P value ≤ 0.05 to define statistical significance). RESULTS: Patient characteristics were not significantly different pre- vs. post-training. Operative time and estimated blood loss significantly decreased. Inflatable implants increased from 19/44 (43.2%, pre-training) to 69/79 (87.3%, post-training) (P < 0.01). Operations per year increased from 9.96 (pre-training) to 24 (post-training) (P < 0.01). Revision/explantation occurred in 11/44 patients (25%, pre-training) vs. 7/79 (8.9%, post-training) (P < 0.05). CONCLUSIONS: These data demonstrate that yearly sessions with a recognized expert can improve surgical outcomes, type, and volume of implants and can reduce explantation/revision rates. This represents an excellent model for improved training of urologic residents in penile prosthetics surgery.

On the mechanism of dimethylarginine dimethylaminohydrolase inactivation by 4-halopyridines.

Small molecules capable of selective covalent protein modification are of significant interest for the development of biological probes and therapeutics. We recently reported that 2-methyl-4-bromopyridine is a quiescent affinity label for the nitric oxide controlling enzyme dimethylarginine dimethylaminohydrolase (DDAH) (Johnson, C. M.; Linsky, T. W.; Yoon, D. W.; Person, M. D.; Fast, W. J. Am. Chem. Soc. 2011, 133, 1553-1562). Discovery of this novel protein modifier raised the possibility that the 4-halopyridine motif may be suitable for wider application. Therefore, the inactivation mechanism of the related compound 2-hydroxymethyl-4-chloropyridine is probed here in more detail. Solution studies support an inactivation mechanism in which the active site Asp66 residue stabilizes the pyridinium form of the inactivator, which has enhanced reactivity toward the active site Cys, resulting in covalent bond formation, loss of the halide, and irreversible inactivation. A 2.18 Å resolution X-ray crystal structure of the inactivated complex elucidates the orientation of the inactivator and its covalent attachment to the active site Cys, but the structural model does not show an interaction between the inactivator and Asp66. Molecular modeling is used to investigate inactivator binding, reaction, and also a final pyridinium deprotonation step that accounts for the apparent differences between the solution-based and structural studies with respect to the role of Asp66. This work integrates multiple approaches to elucidate the inactivation mechanism of a novel 4-halopyridine "warhead," emphasizing the strategy of using pyridinium formation as a "switch" to enhance reactivity when bound to the target protein.