Engineering a therapeutic lectin by uncoupling mitogenicity from antiviral activity.

A key effector route of the Sugar Code involves lectins that exert crucial regulatory controls by targeting distinct cellular glycans. We demonstrate that a single amino-acid substitution in a banana lectin, replacing histidine 84 with a threonine, significantly reduces its mitogenicity, while preserving its broad-spectrum antiviral potency. X-ray crystallography, NMR spectroscopy, and glycocluster assays reveal that loss of mitogenicity is strongly correlated with loss of pi-pi stacking between aromatic amino acids H84 and Y83, which removes a wall separating two carbohydrate binding sites, thus diminishing multivalent interactions. On the other hand, monovalent interactions and antiviral activity are preserved by retaining other wild-type conformational features and possibly through unique contacts involving the T84 side chain. Through such fine-tuning, target selection and downstream effects of a lectin can be modulated so as to knock down one activity, while preserving another, thus providing tools for therapeutics and for understanding the Sugar Code.

An optical atomic clock based on a highly charged ion.

Optical atomic clocks are the most accurate measurement devices ever constructed and have found many applications in fundamental science and technology1-3. The use of highly charged ions (HCI) as a new class of references for highest-accuracy clocks and precision tests of fundamental physics4-11 has long been motivated by their extreme atomic properties and reduced sensitivity to perturbations from external electric and magnetic fields compared with singly charged ions or neutral atoms. Here we present the realization of this new class of clocks, based on an optical magnetic-dipole transition in Ar13+. Its comprehensively evaluated systematic frequency uncertainty of 2.2 × 10-17 is comparable with that of many optical clocks in operation. From clock comparisons, we improve by eight and nine orders of magnitude on the uncertainties for the absolute transition frequency12 and isotope shift (40Ar versus 36Ar) (ref. 13), respectively. These measurements allow us to investigate the largely unexplored quantum electrodynamic (QED) nuclear recoil, presented as part of improved calculations of the isotope shift, which reduce the uncertainty of previous theory14 by a factor of three. This work establishes forbidden optical transitions in HCI as references for cutting-edge optical clocks and future high-sensitivity searches for physics beyond the standard model.

Vertically assembled nanosheet networks for high-density thick battery electrodes.

As one of the prevailing energy storage systems, lithium-ion batteries (LIBs) have become an essential pillar in electric vehicles (EVs) during the past decade, contributing significantly to a carbon-neutral future. However, the complete transition to electric vehicles requires LIBs with yet higher energy and power densities. Here, we propose an effective methodology via controlled nanosheet self-assembly to prepare low-tortuosity yet high-density and high-toughness thick electrodes. By introducing a delicate densification in a three-dimensionally interconnected nanosheet network to maintain its vertical architecture, facile electron and ion transports are enabled despite their high packing density. This dense and thick electrode is capable of delivering a high volumetric capacity >1,600 mAh cm-3, with an areal capacity up to 32 mAh cm-2, which is among the best reported in the literature. The high-performance electrodes with superior mechanical and electrochemical properties demonstrated in this work provide a potentially universal methodology in designing advanced battery electrodes with versatile anisotropic properties.

Feasibility and preliminary effectiveness of a cognitive-behavioral, family-centered partial hospitalization program for adolescents with anorexia nervosa and atypical anorexia nervosa at six- and twelve-month follow-up.

This study examined the feasibility and preliminary effectiveness of a cognitive-behavioral, family-centered partial hospitalization program (PHP) for adolescents with anorexia nervosa (AN) and atypical AN (AAN), and described the outpatient services received following discharge. Participants (N = 31) completed anthropometric and self-report assessments at admission, discharge, and six and twelve months after discharge from the PHP. Descriptive statistics explored markers of feasibility. Paired samples t-tests evaluated changes in weight and eating disorder (ED) symptomatology from admission to discharge, admission to six-month follow-up, and admission to twelve-month follow-up. Descriptive statistics and effect sizes compared symptoms at each timepoint between participants with AN and AAN. Results indicated that we were successful at recruiting greater than 50% of adolescents approached for this study. We collected follow-up data from more than 70% of participants at discharge, but did not meet this retention benchmark at six-month and twelve-month follow-ups. The entire sample demonstrated significant improvements in weight and ED symptomatology from admission to discharge, and generally maintained these improvements at six- and twelve-month follow-up. While descriptive statistics suggested that participants with AN and AAN received similar outpatient services following discharge from the PHP, those with AN experienced greater improvement in self-reported ED symptomatology than those with AAN at six- and twelve-month follow-up. These findings provide preliminary support for the efficacy of PHPs in treating adolescents with AN and AAN. Further research with larger sample sizes should investigate whether adolescents with AAN experience poorer outcomes than those with AN following discharge from a PHP.

High-Grade Dysplasia in Inflammatory Bowel Disease: Indication for Colectomy.

BACKGROUND: Patients with inflammatory bowel disease have an increased risk of colorectal cancer and are recommended to undergo increased surveillance compared to the general population. Currently, inadequate evidence exists to guide management of colonic dysplasia discovered during screening of inflammatory bowel disease patients. OBJECTIVE: The goal of this study was to determine the risk of colorectal cancer in patients with ulcerative colitis or Crohn's disease with dysplasia on colonoscopy. DESIGN: This was a retrospective study. SETTING: This study was conducted at a high-volume, quaternary referral center with an inflammatory bowel disease program. PATIENTS: Patients with a diagnosis of inflammatory bowel disease with colonoscopy within 6 months of colectomy were included. MAIN OUTCOME MEASURES: The primary outcome measures included finding of colorectal cancer at time of colectomy. RESULTS: There were 621 patients, 233 with ulcerative colitis and 388 with Crohn's disease. Of ulcerative colitis patients, 25 had low-grade dysplasia on colonoscopy with 1 (4%) found to have colorectal cancer at colectomy. High-grade dysplasia was noted preoperatively in 14 and colorectal cancer was found in 4 (29%) after colectomy. Compared to no dysplasia, low-grade dysplasia did not increase the risk of colorectal cancer (OR 1.98, p = 0.47), but high-grade dysplasia had an increased risk (OR 19.0, p < 0.001) of colorectal cancer. For the 7 patients with Crohn's disease and low-grade dysplasia, colorectal cancer was found in 1 patient (14%) at colectomy. High-grade dysplasia was noted preoperatively in 4 patients with Crohn's Disease, and colorectal cancer was found in 3 patients (75%) after colectomy. Compared to no dysplasia, low-grade dysplasia did not increase the risk of colorectal cancer (OR 12.4, p = 0.88), but high-grade dysplasia did increase the risk of colorectal cancer (OR 223.2, p < 0.001). LIMITATIONS: This study was limited by its retrospective review. CONCLUSION: In both ulcerative colitis and Crohn's disease, low-grade dysplasia was not associated with colorectal cancer. High-grade dysplasia was associated with an increased risk of colorectal cancer at time of colectomy. While continued surveillance may be appropriate for low-grade dysplasia, high-grade dysplasia necessitates surgical resection given the high likelihood of colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B887 . DISPLASIA DE ALTO GRADO EN LA ENFERMEDAD INFLAMATORIA INTESTINAL INDICACIN DE COLECTOMA: ANTECEDENTES:Los pacientes con enfermedad inflamatoria intestinal tienen un mayor riesgo de cáncer colorrectal y se recomienda someterse a una mayor vigilancia en comparación con la población general. Actualmente, existe evidencia inadecuada para guiar el manejo de la displasia colónica descubierta durante la valoracion de pacientes con enfermedad inflamatoria intestinal.OBJETIVO:Determinar el riesgo de cáncer colorrectal en pacientes con colitis ulcerosa o enfermedad de Crohn con displasia en la colonoscopia.DISEÑO:Este fue un estudio retrospectivo.AJUSTE:Este estudio se llevó a cabo en un centro de referencia cuaternario de alto volumen con un programa de enfermedad inflamatoria intestinal.PACIENTES:Pacientes con diagnóstico de enfermedad inflamatoria intestinal con colonoscopia dentro de los 6 meses posteriores a la colectomía.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado incluyeron el hallazgo de cáncer colorrectal en el momento de la colectomía.RESULTADOS:Hubo 621 pacientes: 233 con colitis ulcerosa y 388 con enfermedad de Crohn. De los pacientes con colitis ulcerosa, 25 tenían displasia de bajo grado en la colonoscopia y 1 (4%) tenía cáncer colorrectal en la colectomía. Se observó displasia de alto grado antes de la operación en 14 y cáncer colorrectal en 4 (29%) después de la colectomía. En comparación con la ausencia de displasia, la displasia de bajo grado no aumentó el riesgo de cáncer colorrectal (Odds Ratio 1,98, p = 0,47), pero la displasia de alto grado tuvo un mayor riesgo (OR 19,0, p <0,001) de cáncer colorrectal. Para los 7 pacientes con enfermedad de Crohn y displasia de bajo grado, se encontró cáncer colorrectal en 1 (14%) en la colectomía. Se observó displasia de alto grado antes de la operación en 4 pacientes con enfermedad de Crohn y cáncer colorrectal en 3 pacientes (75%) después de la colectomía. En comparación con la ausencia de displasia, la displasia de bajo grado no aumentó el riesgo de cáncer colorrectal (Odds Ratio 12.4, p = 0.88), pero la displasia de alto grado sí aumentó el riesgo de cáncer colorrectal (Odds Ratio 223.2, p <.001).LIMITACIONES:Este estudio estuvo limitado por su revisión retrospectiva. CONCLUSIN: Tanto en la colitis ulcerosa como en la enfermedad de Crohn, la displasia de bajo grado no se asoció con el cáncer colorrectal. La displasia de alto grado se asoció con un mayor riesgo de cáncer colorrectal en el momento de la colectomía. Si bien la vigilancia continua puede ser apropiada para la displasia de bajo grado, la displasia de alto grado requiere resección quirúrgica dada la alta probabilidad de cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B887 . (Traducción-Dr Yolanda Colorado ).

A molecularly engineered antiviral banana lectin inhibits fusion and is efficacious against influenza virus infection in vivo.

There is a strong need for a new broad-spectrum antiinfluenza therapeutic, as vaccination and existing treatments are only moderately effective. We previously engineered a lectin, H84T banana lectin (H84T), to retain broad-spectrum activity against multiple influenza strains, including pandemic and avian, while largely eliminating the potentially harmful mitogenicity of the parent compound. The amino acid mutation at position 84 from histidine to threonine minimizes the mitogenicity of the wild-type lectin while maintaining antiinfluenza activity in vitro. We now report that in a lethal mouse model H84T is indeed nonmitogenic, and both early and delayed therapeutic administration of H84T intraperitoneally are highly protective, as is H84T administered subcutaneously. Mechanistically, attachment, which we anticipated to be inhibited by H84T, was only somewhat decreased by the lectin. Instead, H84T is internalized into the late endosomal/lysosomal compartment and inhibits virus-endosome fusion. These studies reveal that H84T is efficacious against influenza virus in vivo, and that the loss of mitogenicity seen previously in tissue culture is also seen in vivo, underscoring the potential utility of H84T as a broad-spectrum antiinfluenza agent.

Gradient Architecture Design in Scalable Porous Battery Electrodes.

Because it has been demonstrated to be effective toward faster ion diffusion inside the pore space, low-tortuosity porous architecture has become the focus in thick electrode designs, and other possibilities are rarely investigated. To advance current understanding in the structure-affected electrochemistry and to broaden horizons for thick electrode designs, we present a gradient electrode design, where porous channels are vertically aligned with smaller openings on one end and larger openings on the other. With its 3D morphology carefully visualized by Raman mapping, the electrochemical properties between opposite orientations of the gradient electrodes are compared, and faster energy storage kinetics is found in larger openings and more concentrated active material near the separator. As further verified by simulation, this study on gradient electrode design deepens the knowledge of structure-related electrochemistry and brings perspectives in high-energy battery electrode designs.

Tortuosity Engineering for Improved Charge Storage Kinetics in High-Areal-Capacity Battery Electrodes.

The increasing demands of electronic devices and electric transportation necessitate lithium-ion batteries with simultaneous high energy and power capabilities. However, rate capabilities are often limited in high-loading electrodes due to the lengthy and tortuous ion transport paths with their electrochemical behaviors governed by complicated electrode architectures still elusive. Here, we report the electrode-level tortuosity engineering design enabling improved charge storage kinetics in high-energy electrodes. Both high areal capacity and high-rate capability can be achieved beyond the practical level of mass loadings in electrodes with vertically oriented architectures. The electrochemical properties in electrodes with various architectures were quantitatively investigated through correlating the characteristic time with tortuosity. The lithium-ion transport kinetics regulated by electrode architectures was further studied via combining the three-dimensional electrode architecture visualization and simulation. The tortuosity-controlled charge storage kinetics revealed in this study can be extended to general electrode systems and provide useful design consideration for next-generation high-energy/power batteries.

Considerations for Designing and Implementing a Multi-institution Undergraduate Medical Education Experience.

Cancer Care Experience (CCE) is a unique elective educational program to further explore the subspecialty of oncology beyond the scope of the traditional undergraduate medical education curriculum. During the COVID-19 pandemic, CCE moved from an in-person to a virtual learning platform. This transition allowed program leaders to offer CCE as a multi-institutional program, with students participating from both Duke University School of Medicine and Penn State College of Medicine. Our study aimed to investigate the effectiveness of virtual learning, student perspectives on multi-institutional collaboration, and the program's impact on the student's understanding of oncology care and clerkship preparedness. Overall, students indicated CCE was an impactful program for them to learn more about oncology and that virtual learning was an effective learning platform. Furthermore, our results suggest students found the multi-institutional aspect valuable and that a multi-institution, hybrid (in-person and virtual) platform was preferred. Our study highlights the success of CCE as a multi-institution program and an effective elective program to expose students to the field of oncology further.

Simultaneous Elucidation of Solid and Solution Manganese Environments via Multiphase Operando Extended X-ray Absorption Fine Structure Spectroscopy in Aqueous Zn/MnO2 Batteries.

Aqueous Zn/MnO2 batteries (AZMOB) with mildly acidic electrolytes hold promise as potential green grid-level energy storage solutions for clean power generation. Mechanistic understanding is critical to advance capacity retention needed by the application but is complex due to the evolution of the cathode solid phases and the presence of dissolved manganese in the electrolyte due to a dissolution-deposition redox process. This work introduces operando multiphase extended X-ray absorption fine structure (EXAFS) analysis enabling simultaneous characterization of both aqueous and solid phases involved in the Mn redox reactions. The methodology was successfully conducted in multiple electrolytes (ZnSO4, Zn(CF3SO3)2, and Zn(CH3COO)2) revealing similar manganese coordination environments but quantitative differences in distribution of Mnn+ species in the solid and solution phases. Complementary Raman spectroscopy was utilized to identify the less crystalline Mn-containing products formed under charge at the cathodes. This was further augmented by transmission electron microscopy (TEM) to reveal the morphology and surface condition of the deposited solids. The results demonstrate an effective approach for bulk-level characterization of poorly crystalline multiphase solids while simultaneously gaining insight into the dissolved transition-metal species in solution. This work provides demonstration of a useful approach toward gaining insight into complex electrochemical mechanisms where both solid state and dissolved active materials are important contributors to redox activity.

Stoma-less IPAA Is Not Associated With Increased Anastomotic Leak Rate or Long-term Pouch Failure in Patients With Ulcerative Colitis.

BACKGROUND: There is debate regarding the utility of diverting loop ileostomy with IPAA construction in patients requiring colectomy for ulcerative colitis. OBJECTIVE: This study aimed to determine whether the omission of diverting loop ileostomy at the time of IPAA construction increases the risk of complications. DESIGN: This was a retrospective study. SETTINGS: The study was conducted in a high-volume, quaternary referral center with an IBD program. PATIENTS: The patients, who underwent IPAA with or without ileostomy, were diagnosed for ulcerative colitis. MAIN OUTCOME MEASURES: Anastomotic leak rate and pouch failure rates were determined between patients who either had a diverting ileostomy at the time of IPAA creation or had stoma-less IPAA. RESULTS: Of the 414 patients included in this study, 91 had stoma-less IPAA. When compared to IPAA with diverting loop ileostomy, patients with stoma-less IPAA were less likely to be taking prednisone and had decreased blood loss. Short- and long-term outcomes were similar when comparing stoma-less IPAA and IPAA with diverting loop ileostomy, with no significant difference in anastomotic leak rate and long-term pouch failure rates. Diverting loop ileostomy was associated with a 14.6% risk of complication at the time of stoma reversal. LIMITATIONS: The study is limited by its retrospective nature. CONCLUSIONS: The results of this study suggest that the omission of a diverting ileostomy is feasible in select patients undergoing IPAA. Stoma-less IPAA does not have a statistically significant higher risk of anastomotic leak or pouch failure when compared to IPAA with diverting loop ileostomy in properly selected patients. Diverting loop ileostomies have their own risks, which partially offset their perceived safety. See Video Abstract at http://links.lww.com/DCR/B891 .LA ANASTOMÓSIS DE RESERVORIO ILEAL AL ANO SIN ESTOMA NO ESTÁ ASOCIADO CON UN AUMENTO EN LA TASA DE FUGA ANASTOMÓTICA O DISFUNCIÓN DE LA BOLSA A LARGO PLAZO EN PACIENTES CON COLITIS ULCERATIVA. ANTECEDENTES: Existe debate en lo que respecta a la utilidad de efectuar una ileostomía en asa en la construcción de una anastomosis de reservorio ileal al ano en pacientes que requieren colectomía para colitis ulcerativa. OBJETIVO: Determinar si el evitar una ileostomía de derivación en el momento de efectuar una anstomósis de reservorio ileal al ano aumenta el riesgo de complicaciones. DISEO: Estudio retrospectivo. REFERENCIA: Centro de referencia de cuarto nivel de grandes volúmenes con programa de enfermedad inflamatoria intestinal. PACIENTES: Con diagnóstico de colitis ulcerativa sometidos a anastomosis de reservorio ileal al ano con o sin ileostomía derivative. PRINCIPALES MEDIDAS DE RESULTADOS: Tasa de fuga anastomótica y disfunción del reservorio en pacientes sometidos a anastomosis de reservorio ileal al ano con ileostomía derivativa en el mismo evento y aquellos sin derivación de protección. RESULTADOS: De los 414 pacientes incluídos en el estudio, 91 no contaban con ileostomía de protección de la anastomosis del reservorio ileal al ano. Al comprarse con aquellos con ileostomía derivativa, aquellos sin estoma requirieron menor dosis de prednisona y presentaron menor pérdida sanguínea. Los resultados a corto y largo plazo fueron similares al comprar ambos grupos sin haber evidencia significativa de fuga anastomótica o falla del reservorio a largo plazo. La derivación con ileostomía en asa se asoció en un 14.6% de riesgo de complicaciones al efectuar el cierre de la misma. LIMITACIONES: Es una revision retrospectiva. CONCLUSIONES: : Los resultados de este estudio sugieren que la omisión de una ileostomía de protección es posible en pacientes seleccionados sometidos a una anastomosis de reservorio ileoanal. La anastomosis sin derivación de protección no confiere un riesgo estadísticamente significativo de fuga anastomótica o disfunción de la misma al compararse con el procedimiento con estoma derivativo en pacientes seleccionados. Las ileostomías de derivación en asa tienen su propia morbilidad que cuestiona la perfección de su seguridad. Consulte Video Resumen at http://links.lww.com/DCR/B891 . (Traducción- Dr. Miguel Esquivel-Herrera ).

Preliminary effectiveness of a cognitive-behavioral, family-centered partial hospitalization program for children and adolescents with avoidant/restrictive food intake disorder.

OBJECTIVE: This study explored the preliminary effectiveness of a partial hospitalization program (PHP) for children/adolescents with avoidant/restrictive food intake disorder (ARFID). We evaluated how ARFID symptoms changed from admission to discharge, and collected follow-up data on symptoms and outpatient care following PHP discharge. METHOD: Twenty-two children/adolescents with ARFID (77.3% White, 63.6% female) completed measures assessing ARFID symptomatology at admission and discharge from a PHP for eating disorders. Six months and twelve months following their discharge, participants were contacted to complete study measures again and take part in an interview assessing follow-up care. RESULTS: Paired samples t tests indicated that participants demonstrated increases in weight and decreases in ARFID symptomatology from admission to discharge with medium to large effects. All participants reported receiving some form of outpatient treatment following discharge, with the type of outpatient services varying across participants. Data from the 86% of participants who completed the six-month follow-up and 50% who completed the twelve-month follow-up suggest that participants generally maintained treatment gains following PHP discharge. DISCUSSION: Participants experienced symptom improvements from admission to discharge and appeared to maintain these gains after discharge. These results provide preliminary evidence that PHPs are an effective treatment option for children and adolescents with ARFID. PUBLIC SIGNIFICANCE STATEMENT: This study provides preliminary evidence that intensive, evidence-based PHPs are effective in treating ARFID. Our findings suggest that children and adolescents with ARFID who receive flexible, cognitive-behavioral, family-centered treatment in a PHP for EDs experience improvements in weight and ARFID symptomatology from admission to discharge. Despite receiving variable and nonstandardized outpatient treatment, individuals with ARFID appear to maintain treatment gains 6 and 12 months after discharge in a PHP.

Tunable Porous Electrode Architectures for Enhanced Li-Ion Storage Kinetics in Thick Electrodes.

Thick electrodes, although promising toward high-energy battery systems, suffer from restricted lithium-ion transport kinetics due to prolonged diffusion lengths and tortuous transport pathways. Despite the emerging low-tortuosity designs, capacity retention under higher current densities is still limited. Herein, we employ a modified ice-templating method to fabricate low-tortuosity porous electrodes with tunable wall thickness and channel width and systematically investigate the critical impacts of the fine structural parameters on the thick electrode electrochemistry. While the porous electrodes with thick walls show diminished capability under a C-rate larger than 1.5 C, those with thinner walls could maintain ∼70% capacity under 2.5 C. The superior capacity retention is ascribed to the fast diffusion into the thin lamellar walls compared with their thicker counterparts. This study provides deeper insights into structure-affected electrochemistry and opens up new perspective of 3D porous architectural designs for high-energy and high-power electrodes.

Lithium vanadium oxide (Li1.1V3O8) thick porous electrodes with high rate capacity: utilization and evolution upon extended cycling elucidated via operando energy dispersive X-ray diffraction and continuum simulation.

The phase distribution of lithiated LVO in thick (∼500 µm) porous electrodes (TPEs) designed to facilitate both ion and electron transport was determined using synchrotron-based operando energy dispersive X-ray diffraction (EDXRD). Probing 3 positions in the TPE while cycling at a 1C rate revealed a homogeneous phase transition across the thickness of the electrode at the 1st and 95th cycles. Continuum modelling indicated uniform lithiation across the TPE in agreement with the EDXRD results and ascribed decreasing accessible active material to be the cause of loss in delivered capacity between the 1st and 95th cycles. The model was supported by the observation of significant particle fracture by SEM consistent with loss of electrical contact. Overall, the combination of operando EDXRD, continuum modeling, and ex situ measurements enabled a deeper understanding of lithium vanadium oxide transport properties under high rate extended cycling within a thick highly porous electrode architecture.

DiabetesSistersVoices: Virtual Patient Community to Identify Research Priorities for Women Living With Diabetes.

BACKGROUND: Women with or at high risk of diabetes have unique health concerns across their life course. Effective methods are needed to engage women living with diabetes to develop and carry out a patient-centered research agenda. OBJECTIVE: This study aimed to (1) describe the creation of DiabetesSistersVoices, a virtual patient community for women living with and at risk for diabetes and (2) assess the feasibility and acceptability of DiabetesSistersVoices for engaging women in talking about their experiences, health care, and research priorities. METHODS: We partnered with a national advocacy organization to create DiabetesSistersVoices and to develop recruitment strategies, which included use of social media, Web-based newsletters, and weblinks through partnering organizations. Study inclusion criteria were as follows: Being a woman aged ≥18 years, residing in the United States, and self-reporting a diagnosis of diabetes or risk of diabetes. Eligible participants were given access to DiabetesSistersVoices and completed online surveys at enrollment and 6 months. We assessed trends in participants' activities, including posting questions, sharing experiences about living with diabetes, and searching for posted resources. RESULTS: We enrolled 332 women (white: 86.5%; type 1 diabetes: 76.2%; median age: 51 years [interquartile range: 31 to 59 years]) over 8 months. Most (41.6%, 138/332) were classified as being active users (ie, posting) of the virtual community, 36.1% (120/332) as observers (ie, logged in but no posts), and 22.3% (74/332) as never users (ie, completed baseline surveys but then never logged in). Online activities were constant during the study, although participants had the highest website usage during the first 10 weeks after their enrollment. CONCLUSIONS: We demonstrated the feasibility and acceptability of an online patient community for women living with diabetes by showing durability of recruitment and online usage over 6 months of testing. Next steps are to address barriers to joining a virtual patient community for women of color and women with type 2 diabetes to enhance inclusiveness and gain diverse perspectives to inform diabetes research.

Identification of peptide-binding sites within BSA using rapid, laser-induced covalent cross-linking combined with high-performance mass spectrometry.

We are developing a rapid, time-resolved method using laser-activated cross-linking to capture protein-peptide interactions as a means to interrogate the interaction of serum proteins as delivery systems for peptides and other molecules. A model system was established to investigate the interactions between bovine serum albumin (BSA) and 2 peptides, the tridecapeptide budding-yeast mating pheromone (α-factor) and the decapeptide human gonadotropin-releasing hormone (GnRH). Cross-linking of α-factor, using a biotinylated, photoactivatable p-benzoyl-L-phenylalanine (Bpa)-modified analog, was energy-dependent and achieved within seconds of laser irradiation. Protein blotting with an avidin probe was used to detect biotinylated species in the BSA-peptide complex. The cross-linked complex was trypsinized and then interrogated with nano-LC-MS/MS to identify the peptide cross-links. Cross-linking was greatly facilitated by Bpa in the peptide, but some cross-linking occurred at higher laser powers and high concentrations of a non-Bpa-modified α-factor. This was supported by experiments using GnRH, a peptide with sequence homology to α-factor, which was likewise found to be cross-linked to BSA by laser irradiation. Analysis of peptides in the mass spectra showed that the binding site for both α-factor and GnRH was in the BSA pocket defined previously as the site for fatty acid binding. This model system validates the use of laser-activation to facilitate cross-linking of Bpa-containing molecules to proteins. The rapid cross-linking procedure and high performance of MS/MS to identify cross-links provides a method to interrogate protein-peptide interactions in a living cell in a time-resolved manner.

JOURNAL CLUB: Scatter Radiation Dose From Digital Screening Mammography Measured in a Representative Patient Population.

OBJECTIVE: The purpose of this study was to quantify the amount of scatter radiation received at the skin surface overlying the thyroid gland, salivary gland, lens of the eye, sternum, and uterus during a routine screening digital mammographic examination measured in a representative patient population. SUBJECTS AND METHODS: The subjects were 207 women without symptoms with varied body mass indexes who underwent annual screening mammography while wearing six optically stimulated luminescence dosimeters placed at the bridge of the nose, right submandibular gland, right and left thyroid lobes, mid sternum, and 2 cm caudal to the umbilicus to assess scatter radiation dose to the skin. RESULTS: The average scatter radiation doses at the skin surface during digital screening mammography in the representative population of women were as follows: overlying the right lobe of the thyroid, 0.24 mGy; left lobe of the thyroid, 0.25 mGy; salivary gland, 0.2 mGy; bridge of the nose, 0.025 mGy; sternum, 0.87 mGy; and umbilicus, 0.011 mGy. The scatter radiation doses at the umbilicus and the bridge of the nose were too low to measure with statistical confidence. Scatter radiation dose increased with increasing body mass index and increasing breast compression thickness. CONCLUSION: Scatter radiation dose at the skin overlying organs of interest is a small fraction of the entrance skin dose to the breast. The low levels of scatter radiation measured do not support delaying clinically indicated mammography during early pregnancy.

A Radiation Safety Training Program Results in Reduced Radiation Exposure for Orthopaedic Residents Using the Mini C-arm.

BACKGROUND: Fluoroscopy during fracture reduction allows a physician to assess fractures and immediately treat a pediatric patient. However, concern regarding the effects of radiation exposure has led us to find ways to keep radiation exposures as low as reasonably achievable. One potentially simple way, which to our knowledge has not been explored, to decrease radiation exposure is through formal education before mini C-arm use. QUESTIONS/PURPOSES: We questioned whether a radiation safety educational program decreases radiation (1) time and (2) exposure among residents and patients. PATIENTS AND METHODS: This is a retrospective study in which second-year residents underwent a 3-hour educational program regarding mini C-arm use and radiation safety taught by our institution's health physics department. We evaluated the records of all patients who underwent a pediatric both-bone forearm or distal radius fracture reduction in the emergency department 3 months before the educational program or after the program. To be included in the study, records included simple both-bone forearm fractures, simple distal radius fractures, and patient age younger than 18 years, and could not include patients with multiple fractures in the same limb. This resulted in study groups of 53 and 45 patients' records in the groups before and after the educational session, respectively. Radiation emission from the mini C-arm between both groups were compared. RESULTS: Exposure time with the mini C-arm was longer in patients treated before the educational intervention than in those treated after the intervention (patients with both-bone forearm fractures: mean = 41.2, SD = 24.7, 95% CI, 23.14-59.26 vs mean = 28.9, SD = 14.4, 95% CI, 15.91-41.89, p = 0.066; patients with distal radius fractures: mean = 38.1, SD = 26.1, 95% CI, 25.1-51.1 vs mean = 26.7, SD = 15.8, 95% CI, 16.44-36.96, p = 0.042). Calculated radiation exposure with the mini C-arm was larger in patients treated before the educational intervention than in those treated after the intervention (patients with both-bone forearm fractures: mean = 90.9, SD = 60.9, 95% CI, 51.06-130.74 vs mean = 30.4, SD = 18.5, 95% CI, 16.73-44.07, p < 0.001; patients with distal radius fractures: mean = 83.1, SD = 58.9, 95% CI, 54.75-111.45 vs mean = 32.6, SD = 26.4, 95% CI, 20.07-45.13, p < 0.001). CONCLUSIONS: A radiation-safety program resulted in decreased radiation exposure to residents and patients, and in decreased mini C-arm exposure time during pediatric fracture reductions. LEVEL OF EVIDENCE: Level III, therapeutic study.

Genomic flexibility of human endogenous retrovirus type K.

UNLABELLED: Human endogenous retrovirus type K (HERV-K) proviruses are scattered throughout the human genome, but as no infectious HERV-K virus has been detected to date, the mechanism by which these viruses replicated and populated the genome remains unresolved. Here, we provide evidence that, in addition to the RNA genomes that canonical retroviruses package, modern HERV-K viruses can contain reverse-transcribed DNA (RT-DNA) genomes. Indeed, reverse transcription of genomic HERV-K RNA into the DNA form is able to occur in three distinct times and locations: (i) in the virus-producing cell prior to viral release, yielding a DNA-containing extracellular virus particle similar to the spumaviruses; (ii) within the extracellular virus particle itself, transitioning from an RNA-containing particle to a DNA-containing particle; and (iii) after entry of the RNA-containing virus into the target cell, similar to canonical retroviruses, such as murine leukemia virus and HIV. Moreover, using a resuscitated HERV-K virus construct, we show that both viruses with RNA genomes and viruses with DNA genomes are capable of infecting target cells. This high level of genomic flexibility historically could have permitted these viruses to replicate in various host cell environments, potentially assisting in their many integration events and resulting in their high prevalence in the human genome. Moreover, the ability of modern HERV-K viruses to proceed through reverse transcription and package RT-DNA genomes suggests a higher level of replication competency than was previously understood, and it may be relevant in HERV-K-associated human diseases. IMPORTANCE: Retroviral elements comprise at least 8% of the human genome. Of all the endogenous retroviruses, HERV-K viruses are the most intact and biologically active. While a modern infectious HERV-K has yet to be found, HERV-K activation has been associated with cancers, autoimmune diseases, and HIV-1 infection. Thus, determining how this virus family became such a prevalent member of our genome and what it is capable of in its current form are of the utmost importance. Here, we provide evidence that HERV-K viruses currently found in the human genome are able to proceed through reverse transcription and historically utilized a life cycle with a surprising degree of genomic flexibility in which both RNA- and DNA-containing viruses were capable of mediating infection.