bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement in Overground Walking After Treadmill-Based Gait Training in a Child With Agenesis of the Corpus Callosum
Authors: Henderson Gena , Beerse Matthew , Liang Huaqing , Ferreira Diego , Wu Jianhua
Published: October 2019

Background

Agenesis of the corpus callosum (ACC) is a rare congenital brain defect that produces a wide variety of cognitive and motor impairments. Literature regarding the response of pediatric populations with ACC to physical rehabilitation is scarce. Treadmill-based gait training (TT) has been shown to improve walking ability in some pediatric populations but has not been investigated in children with ACC.

Objective

The purpose of this study was to investigate the effect of a novel treadmill intervention paradigm on the gait parameters of a child with ACC.

Design

A single-participant design with 2 phases was used.

Methods

The settings were the participant’s home and the laboratory. The participant was a 13-year-old girl who had ACC and cortical visual impairment and who ambulated independently using a reverse walker for household and short community distances. A home-based TT intervention (2 phases of 3 months of training over 6 months) was implemented, and a laboratory-based gait analysis was conducted at 4 time points: baseline, after each of the 2 training phases, and 3 months after the cessation of training. The intervention consisted of weekly bouts of TT. Phase I incorporated forward, backward, and incline walking for 15 minutes each; in phase II, this protocol was continued, but short-burst interval training for 10 minutes was added. Data collected at each laboratory visit included spatiotemporal parameters and kinematics (joint angles) during overground and treadmill walking.

Results

After both phases of training, increased step length, decreased step width, and foot progression angle and decreased variability of most spatiotemporal parameters were observed for the participant. Further, after phase II, increased peak extension at the hip, knee, and ankle, decreased crouched gait, and improved minimum foot clearance during overground walking were observed. Most gait improvements were retained for 3 months after the cessation of the intervention.

Limitations

The small sample size of this study and wide variety of presentations within individuals with ACC limit the generalizability of our findings.

Conclusions

TT may be a safe and effective treatment paradigm for children with ACC. Future research should investigate the effect of intervention dosage on gait improvements and generalization in individuals with ACC.
Politics, State Ownership, and Corporate Investments
Authors: Alok Shashwat , Ayyagari Meghana
Published: October 2019

We document a political cycle in the investment decisions of state-owned enterprises (SOEs) by using the constitutionally mandated election schedule in India as a source of exogenous variation in politicians’ incentive to cater to voters. Using a project-level investment database, we find that SOEs announce more capital expenditure projects in election years, especially in infrastructure, and in districts with close elections, high-ranking politicians, and left-wing incumbents. SOE projects in election years have negative announcement returns, suggesting a loss in shareholder value. These patterns are not seen in nongovernment firms or in off-election years. (JEL G31, G38, D72, D73, P16)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
P33 Adolescent and young adult health training needs of healthcare professionals including rheumatology
Authors: Smith Elizabeth , Willis Emily , McDonagh Janet
Published: October 2019

Background

The need for training in adolescent and young adult (AYA) health is highlighted in paediatrics, adult medical trainees and the EULAR transition guidance. We aim to identify the current training needs of healthcare professionals regarding AYA health in a UK region including paediatric and adult rheumatology professionals.

Methods

An online survey designed using SelectSurvey.NET for healthcare professionals was distributed by email using a snowballing technique after piloting (1 nurse, 3 doctors). A control question was included on safeguarding, which is mandatory training for all healthcare professionals irrespective of setting.

Results

The overall response rate was 20% (166/820) and included 56% (n = 88/158 doctors -39% of whom were trainees), and 29% (n = 46/158) nurses. 8 identified themselves as rheumatology professionals (8/293, 3% rheumatology-specific response rate). 51% (n = 85/166) of healthcare professionals (including 2 rheumatology professionals) reported having received no formal training in AYA health (43% were doctors, 67% nurses). Of those who had previous training, the main training method was lecture based, with only 7% having accessed the UK Adolescent Health e-learning project. In comparison to 85% and 78% reporting adequate knowledge and skill respectively in safeguarding, less than 40% reported adequate knowledge and/or skills in key areas of AYA health (see Table 1). Respondents who had received training perceived themselves to have better knowledge and skills across many areas of AYA than those who had not received such training. Finally, in some areas of AYA health, there was a large discrepancy between perceived knowledge and skill level.

P33 Table 1 Area of AYA Health % of Healthcare Professionals with Adequate Knowledge % of Healthcare Professionals with Adequate Skill Rheumatology (n = 8) Rest (n = 137) Rheumatology (n = 8) Rest (n = 126) Safeguarding 87.5% 85% 75% 78% Confidentiality & consent 75% 75% 75% 70% Home/family 37.5% 61% 50% 48% Health management 37.5% 56% 37.5% 52% Transitional care 62.5% 54% 75% 47% Eating 12.5% 54% 12.5% 40% Exercise 25% 53% 25% 44% Sleep 50% 43% 37.5% 40% Peer relations 25% 43% 25% 34% Safety 37.5% 40% 37.5% 29% Mental health 12.5% 39% 25% 36% Education/vocation 37.5% 34% 37.5% 27% Sexual health 25% 35% 12.5% 28% Social media 12.5% 33% 25% 30% Substance use 0% 31% 0% 20%

Conclusion

There is still a need to both raise awareness of and improve training opportunities for all healthcare professionals who interact with adolescents and young adults, including rheumatology. This training should be both practical and knowledge based to overcome the discrepancy between knowledge and skill levels.

Conflicts of Interest

The authors declare no conflicts of interest.
INTRAOPERATIVE CHOLANGIOGRAPHY DURING CHOLECYSTECTOMY RESULTS IN LOW EXPOSURE TO RADIATION: A RETROSPECTIVE COHORT STUDY
Authors: Mattila Anne , Larjava Heli , Helminen Olli , Kairaluoma Matti
Published: October 2019

This study aimed to determine the exposure to radiation delivered to the patient during routine intraoperative cholangiography (IOC) in cholecystectomy and examine the factors affecting radiation dose and fluoroscopy time (FT). From January 2016 to December 2017, 598 IOC examinations were performed. This study included 324 intraoperative cholangiographies performed with c-arm equipment not exceeding 10 years of age. When residents performed the procedures, the mean kerma area product (KAP) was 0.36 (standard deviation [SD] 0.70) Gycm 2 and in specialist surgeons group 0.36 (SD 0.47) Gycm2, P = 0.47. In residents group, the mean FT was 11.4 (SD 10.1) seconds and in specialist surgeons group, 9.2 (SD 11.9) seconds, P < 0.01. Linear regression analysis showed association between increased KAP-values and the presence of common bile duct (CBD) stones and body mass index (BMI). Age, BMI, laparoscopic surgery, acute cholecystitis, presence of CBD stones, resident surgeon performing IOC and ASA III–IV were associated with higher FT. National diagnostic reference level for IOC has not been introduced in Finland so far. Our mean KAP values (0.36 Gycm2) were 3–4 times lower and FT (10.1 seconds) were 3–5 times lower than the few reported in the literature. Routine use of IOC during cholecystectomy results in relatively low-radiation dose performed either by residents or specialist surgeons, irrespective of whether CBD stones were visualized or not.
Between promise and performance: Science and technology policy implementation through network governance
Authors: Whetsell Travis A , Leiblein Michael J , Wagner Caroline S
Published: October 2019

This research analyzes the effects of US science and technology policy on the technological performance of organizations in a global strategic alliance network. During the mid-1980s, the US semiconductor industry appeared to be collapsing. Industry leaders and policymakers moved to support and protect US firms by creating a program called Sematech. While many scholars regard Sematech as a success, how the program succeeded remains unclear. This study re-contextualizes Sematech as a network administrative organization which lowered cooperation costs and enhanced resource combination for innovation at the cutting edge. This study combines network analysis and longitudinal regression techniques to test the effects of public policy on organizational network position and technological performance in an unbalanced panel of semiconductor firms between 1986 and 2001. This research suggests that governments might achieve policy through inter-organizational innovations aimed at the development and administration of robust governance networks.
A clinical rule for the prediction of meningitis in HIV patients in the era of combination antiretroviral therapy
Authors: Abd El-Wahab Ekram W , Farrag Talaat , Metwally Mohammed
Published: October 2019

Background

The diagnosis of meningitis in HIV patients is challenging due to altered immune responses. Diagnostic scoring systems were recently proposed for use in research settings to help prompt and easy differential diagnosis. The objective of this study was to create a clinical prediction rule (CPR) for meningitis in HIV-infected patients and to address the enigma of differentiating bacterial (BM), TB (TBM) and cryptococcal (CCM) meningitis based on clinical features alone, which may be enhanced by easy-to-obtain laboratory testing.

Methods

We retrospectively enrolled 352 HIV patients presenting with neurological manifestations suggesting meningitis over the last 18 y (2000–2018). Relevant clinical and laboratory information were retrieved from inpatient records. The features independently predicting meningitis or its different types in microbiologically proven meningitis cases were modelled by multivariate logistic regression to create a CPR in an exploratory data set. The performance of the meningitis diagnostic score was assessed and validated in a subset of retrospective data.

Results

AIDS clinical stage, injecting drug use, jaundice and cryptococcal antigen seropositivity were equally important as classic meningitic symptoms in predicting meningitis. Arthralgia and elevated cerebrospinal fluid Lactate dehydrogenase (LDH) were strong predictors of BM. Patients with cryptococcal antigenemia had 25 times the probability of having CCM, whereas neurological deficits were highly suggestive of TBM.

Conclusion

The proposed CPRs have good diagnostic potential and would support decision-making in resource-poor settings.
Screening for Resistance to Meloidogyne enterolobii in Capsicum annuum Landraces From Mexico
Authors: Carrillo-Fasio J. A. , Martínez-Gallardo J. A. , Ayala-Tafoya F. , López-Orona C. A. , Allende-Molar R. , Retes-Manjarrez J. E.
Published: October 2019

Meloidogyne enterolobii has become an economically important plant parasitic nematode worldwide because of its high aggressiveness, increasing geographic distribution, wide host range, and pathogenicity in pepper (Capsicum annuum) cultivars carrying resistance genes to Meloidogyne incognita, Meloidogyne arenaria, and Meloidogyne javanica. The objectives of this study were to identify landraces of peppers resistant to M. enterolobii and analyze the relationship between resistance indicators and the phenotype parameters of plant height, stem width, leaf length, leaf width, relative chlorophyll, and number of flowers. Ninety landraces of C. annuum were collected from several states of Mexico and were inoculated with 2,000 eggs of M. enterolobii. Eleven resistant landraces were selected and confirmed with a second inoculation experiment. Seventy-five days after inoculation, in both experiments, the resistance of landraces UTC66, UTC90, UTC67, UTC88, and UTC81 to M. enterolobii was consistent. Although genotypes UTC24, UTC79, UTC65, UTC68, UTC69, and UTC25 were susceptible, these landraces had a significantly higher proportion of resistant plants, less root galling, and a lower reproductive index, in comparison with the rest of the 79 genotypes and the susceptible control, which were highly susceptible in both experiments. There was no correlation between resistant indicators and phenotypic parameters, although plant height, relative chlorophyll, and number of flowers were in general significantly affected compared with noninoculated controls, indicating that the nematodes reduce the growth and yield of peppers. Results indicate that all resistant plants from these landraces are promising sources of resistance for the development of pepper cultivars resistant to M. enterolobii.
Postharvest Incidence of Stem End Rot in ‘Hayward’ Kiwifruit Is Related to PreharvestBotrytis cinereaColonization of Floral Parts and Latent Infection
Authors: Riquelme-Toledo Danae , Valdés-Gómez Héctor , Fermaud Marc , Zoffoli Juan Pablo
Published: October 2019

Stem end rot (SER) caused by Botrytis cinerea is the primary postharvest disease in the Chilean kiwifruit industry. Relationships between the postharvest occurrence of SER in ‘Hayward’ kiwifruit and the temporal dynamics of earlier B. cinerea colonization of the floral parts (petals, sepals, receptacles, styles) was studied in five orchards over two consecutive seasons in Chile. Weather conditions in the first season favored B. cinerea infection with roughly constant colonization of floral parts up to about 120 days after full bloom, but colonization then increased up until harvest. In the second season, colonization was roughly constant throughout. Latent infections of the fruit occurred in both seasons but were high in the first season and low in the second. Incidence of latent infections at harvest were the best predictors (r > 0.8) of postharvest SER. The number of preharvest infection periods calculated using temperature, leaf wetness, and relative humidity satisfactorily predicted SER incidence by an exponential model, R2= 0.90, P < 0.001. Results indicated environmental variables play key roles in the temporal dynamics of B. cinerea colonization. Quantification of latent B. cinerea infections in asymptomatic fruit close to harvest, is a practicable way to predict later incidence of SER during storage.
Evaluation of Recombinase Polymerase Amplification Assay for DetectingMeloidogyne javanica
Authors: Chi Yuan-kai , Zhao Wei , Ye Meng-di , Ali Farman , Wang Tao , Qi Ren-de
Published: October 2019

Meloidogyne javanica is one of the most widespread and economically important nematodes in many countries, including China. In this study, a recombinase polymerase amplification (RPA) assay was evaluated for the detection of M. javanica based on the sequences of a sequence-characterized amplified regions marker gene segment. The RPA assay specifically detected M. javanica from individual juvenile or adult female, M. javanica-induced galls, and nematodes in the soil samples. The detection limit of M. javanica RPA assay was 1 pg of purified genomic DNA, 0.01 adult female, or 0.1 second-stage juvenile, which was 10 times more sensitive than conventional PCR assay. Furthermore, combined with lateral flow dipstick (LFD), a visual detection method of LFD-RPA assay was developed, which is suitable for onsite surveys and routine diagnostics. Results indicate that the RPA assay is rapid, sensitive, and reliable for detection and molecular identification of M. javanica.
Reduction of Botrytis cinerea Colonization of and Sporulation on Bunch Trash
Authors: Fedele Giorgia , González-Domínguez Elisa , Si Ammour Melissa , Languasco Luca , Rossi Vittorio
Published: October 2019

Botrytis bunch rot (BBR) of grapevine, caused by Botrytis cinerea, is commonly managed by fungicide (FUN) sprays at flowering (A), at prebunch closure (B), at veraison (C), and before harvest. Applications at A, B, and C are recommended to reduce B. cinerea colonization of bunch trash and the production of conidia during berry ripening. The effects of these applications were previously evaluated as reductions in BBR severity at harvest rather than as reductions in bunch trash colonization and sporulation by B. cinerea. This study investigated the effects of FUNs (a commercial mixture of fludioxonil and cyprodonil), biological control agents (BCAs; Aureobasium pullulans and Trichoderma atroviride), and botanicals (BOTs; a commercial mixture of eugenol, geraniol, and thymol) applied at different timings (A, B, C, or ABC) compared with a nontreated control (NT) on B. cinerea bunch trash colonization and sporulation in vineyards. The ability of B. cinerea to colonize the bunch trash (as indicated by B. cinerea DNA content) and sporulate (as indicated by the number of conidia produced under optimal laboratory conditions) was highly variable, and this variability was higher between years (2015 to 2018) than among the three vineyards and three sampling times (i.e., 1 week after applications at A, B, and C). B. cinerea sporulation on bunch trash was significantly lower in plots treated with FUN than in NT in only 3 of 18 cases (3 vineyards × 2 years × 3 sampling times). FUN applications, however, significantly reduced B. cinerea colonization of bunch trash compared with NT; for colonization, BCA efficacy was similar to that of FUN, but BOT efficacy was variable. For all products, colonization reduction was the same with application at A versus ABC, meaning that the effect of an early season application lasted from flowering to 1 week after veraison. These results indicate that the early season control of B. cinerea is important to reduce the saprophytic colonization of bunch trash, especially when the risk of BBR is high.
Spatial and Temporal Physiognomies of Whitefly and Tomato Yellow Leaf Curl Virus Epidemics in Southwestern Florida Tomato Fields
Authors: Anco Daniel J. , Rouse Lisa , Lucas Leon , Parks Felicia , Mellinger H. Charles , Adkins Scott , Kousik Chandrasekar S. , Roberts Pamela D. , Stansly Philip A. , Ha Miae , Turechek William W.
Published: October 2019

Epidemics of tomato yellow leaf curl virus (TYLCV; species Tomato yellow leaf curl begomovirus) have been problematic to tomato production in the southeastern United States since the first detection of the virus in Florida in the late 1990s. Current strategies for management focus on farm-centric tactics that have had limited success for controlling either TYLCV or its whitefly vector. Areawide pest management (AWPM)—loosely defined as a coordinated effort to implement management strategies on a regional scale—may be a viable management alternative. A prerequisite for development of an AWPM program is an understanding of the spatial and temporal dynamics of the target pathogen and pest populations. The objective of this study was to characterize populations of whitefly and TYLCV in commercial tomato production fields in southwestern Florida and utilize this information to develop predictors of whitefly density and TYLCV disease incidence as a function of environmental and geographical factors. Scouting reports were submitted by cooperating growers located across approximately 20,000 acres in southwestern Florida from 2006 to 2012. Daily weather data were obtained from several local weather stations. Moran’s I was used to assess spatial relationships and polynomial distributed lag regression was used to determine the relationship between weather variables, whitefly, and TYLCV. Analyses showed that the incidence of TYLCV increased proportionally with mean whitefly density as the season progressed. Nearest-neighbor analyses showed a strong linear relationship between the logarithms of whitefly densities in neighboring fields. A similar relationship was found with TYLCV incidences. Correlograms based on Moran’s I showed that these relationships extended beyond neighboring fields and out to approximately 2.5 km for TYLCV and up to 5 km for whitefly, and that values of I were generally higher during the latter half of the production season for TYLCV. Weather was better at predicting whitefly density than at predicting TYLCV incidence. Whitefly density was best predicted by the number of days with an average temperature between 16 and 24°C (T16to24), relative humidity (RH) over the previous 31 days, and vapor pressure deficit over the last 8 days. TYLCV incidence was best predicted by T16to24, RH, and maximum wind speed over the previous 31 days. Results of this study helped to identify the extent to which populations of whitefly and TYLCV exist over the agricultural landscape of southwestern Florida, and the environmental conditions that favor epidemic growth. This information was used to propose an approach to AWPM for timing control measures for managing TYLCV epidemics.
Broad‐spectrum chemokine inhibition blocks inflammation‐induced angiogenesis, but preserves ischemia‐driven angiogenesis
Authors: Ravindran Dhanya , Cartland Siân P. , Bursill Christina A. , Kavurma Mary M.
Published: October 2019

M3 is a broad‐spectrum chemokine‐binding protein that inactivates inflammatory chemokines, including CCL2, CCL5, and CX3CL1. The aim of this study was to compare whether M3 could inhibit angiogenesis driven by inflammation or ischemia. Here, apolipoprotein E–/– mice were injected with adenoviral M3 (AdM3) or control adenoviral green fluorescent protein (AdGFP) 3 d prior to stimulating angiogenesis using 2 established models that distinctly represent inflammatory or ischemia‐driven angiogenesis, namely the periarterial femoral cuff and hind limb ischemia. AdM3 reduced intimal thickening, adventitial capillary density, and macrophage accumulation in femoral arteries 21 d after periarterial femoral cuff placement compared with AdGFP‐treated mice (P < 0.05). AdM3 also reduced mRNA expression of proangiogenic VEGF, inflammatory markers IL‐6 and IL‐1β, and vascular smooth muscle cell (VSMC)‐activated synthetic markers Krüppel‐like family of transcription factor 4 (KLF4) and platelet‐derived growth factor receptor β (PDGFRβ) in the inflammatory cuff model. In contrast, capillary density, VSMC content, blood flow perfusion, and VEGF gene expression were unaltered between groups in skeletal muscle following hind limb ischemia. In vitro, AdM3 significantly reduced human microvascular endothelial cell 1 proliferation, migration, and tubule formation by ~17, 71.3, and 8.7% (P < 0.05) in macrophage‐conditioned medium associating with reduced VEGF and hypoxia‐inducible factor 1α mRNA but not in hypoxia (1% O2). Compared with AdGFP, AdM3 also inhibited VSMC proliferation and migration and reduced mRNA expression of KLF4 and PDGFRβ under inflammatory conditions. In contrast, AdM3 had no effect on VSMC processes in response to hypoxia in vitro. Our findings show that broad‐spectrum inhibition of inflammatory chemokines by M3 inhibits inflammatory‐driven but not ischemia‐driven angiogenesis, presenting a novel strategy for the treatment of diseases associated with inflammatory‐driven angiogenesis.—Ravindran, D., Cartland, S. P., Bursill, C. A., Kavurma, M. M. Broad‐spectrum chemokine inhibition blocks inflammation‐induced angiogenesis, but preserves ischemia‐driven angiogenesis. FASEB J. 33, 13423–13434 (2019). www.fasebj.org
Salmonella effector SpvB interferes with intracellular iron homeostasis via regulation of transcription factor NRF2
Authors: Yang Sidi , Deng Qifeng , Sun Lanqing , Dong Kedi , Li Yuanyuan , Wu Shuyan , Huang Rui
Published: October 2019

Iron is a necessary nutrient for humans and nearly all bacterial species. During Salmonella infection, macrophages limit the availability of iron to intracellular pathogens in one of the central components of nutritional immunity. However, Salmonella also have mechanisms to interfere with the antimicrobial effect of host iron withdrawal and meet their own nutrient requirements by scavenging iron from the host. Here, we provide what is, to our knowledge, the first report that SpvB, a pSLT‐encoded cytotoxic protein whose function is associated with the intracellular stage of salmonellosis, perturbs macrophage iron metabolism, thereby facilitating Salmonella survival and intracellular replication. In investigating the underlying mechanism, we observed that the Salmonella effector SpvB down‐regulated nuclear factor erythroid‐derived 2‐related factor 2 (NRF2), and its C‐terminal domain was necessary and sufficient for NRF2 degradation via the proteasome pathway. Decreased NRF2 expression in the nucleus resulted in a decrease in its transcriptional target ferroportin, encoding the sole macrophage iron exporter, thus ultimately decreasing iron efflux and increasing the intracellular iron content. Additionally, SpvB contributes to the pathogenesis of Salmonella including severe serum hypoferremia, increased splenic and hepatic bacterial burden, and inflammatory injury in vivo. Together, our observations uncovered a novel contribution of SpvB to Salmonella pathology via interference with host intracellular iron metabolism.—Yang, S., Deng, Q., Sun, L., Dong, K., Li, Y., Wu, S., Huang, R. Salmonella effector SpvB interferes with intracellular iron homeostasis via regulation of transcription factor NRF2. FASEB J. 33, 13450–13464 (2019). www.fasebj.org
Serine‐47 phosphorylation of cytochrome c in the mammalian brain regulates cytochrome c oxidase and caspase‐3 activity
Authors: Kalpage Hasini A. , Vaishnav Asmita , Liu Jenney , Varughese Ashwathy , Wan Junmei , Turner Alice A. , Ji Qinqin , Zurek Matthew P. , Kapralov Alexandr A. , Kagan Valerian E. , Brunzelle Joseph S. , Recanati Maurice‐Andre , Grossman Lawrence I. , Sanderson Thomas H. , Lee Icksoo , Salomon Arthur R. , Edwards Brian F. P. , Hüttemann Maik
Published: October 2019

Cytochrome c (Cytc) is a multifunctional protein that operates as an electron carrier in the mitochondrial electron transport chain and plays a key role in apoptosis. We have previously shown that tissue‐specific phosphorylations of Cytc in the heart, liver, and kidney play an important role in the regulation of cellular respiration and cell death. Here, we report that Cytc purified from mammalian brain is phosphorylated on S47 and that this phosphorylation is lost during ischemia. We have characterized the functional effects in vitro using phosphorylated Cytc purified from pig brain tissue and a recombinant phosphomimetic mutant (S47E). We crystallized S47E phosphomimetic Cytc at 1.55 Å and suggest that it spatially matches S47‐phosphorylated Cytc, making it a good model system. Both S47‐phosphorylated and phosphomimetic Cytc showed a lower oxygen consumption rate in reaction with isolated Cytc oxidase, which we propose maintains intermediate mitochondrial membrane potentials under physiologic conditions, thus minimizing production of reactive oxygen species. S47‐phosphorylated and phosphomimetic Cytc showed lower caspase‐3 activity. Furthermore, phosphomimetic Cytc had decreased cardiolipin peroxidase activity and is more stable in the presence of H2O2. Our data suggest that S47 phosphorylation of Cytc is tissue protective and promotes cell survival in the brain.—Kalpage, H. A., Vaishnav, A., Liu, J., Varughese, A., Wan, J., Turner, A. A., Ji, Q., Zurek, M. P., Kapralov, A. A., Kagan, V. E., Brunzelle, J. S., Recanati, M.‐A., Grossman, L. I., Sanderson, T. H., Lee, I., Salomon, A. R., Edwards, B. F. P, Hüttemann, M. Serine‐47 phosphorylation of cytochrome c in the mammalian brain regulates cytochrome c oxidase and caspase‐3 activity. FASEB J. 33, 13503‐13514 (2019). www.fasebj.org
Gα13‐mediated LATS1 down‐regulation contributes to epithelial‐mesenchymal transition in ovarian cancer
Authors: Yagi Hiroshi , Onoyama Ichiro , Asanoma Kazuo , Hori Emiko , Yasunaga Masafumi , Kodama Keisuke , Kijima Masako , Ohgami Tatsuhiro , Kaneki Eisuke , Okugawa Kaoru , Yahata Hideaki , Kato Kiyoko
Published: October 2019

Gα13, a heterotrimeric G‐protein of the Gα12/13 subfamily, is associated with aggressive phenotypes in various human cancers. However, the mechanisms by which Gα13 promotes cancer progression have not been fully elucidated. Here, we demonstrate that the activation of Ga13 induces epithelial‐mesenchymal transition in ovarian cancer (OvCa) cells through down‐regulation of large tumor suppressor kinase (LATS) 1, a critical component of the Hippo signaling pathway. A synthetic biology approach using a mutant GPCR and chimeric G‐protein revealed that Gα13‐regulated phosphorylation of LATS1 at serine 909 within its activation loop induced recruitment of the itchy E3 ubiquitin protein ligase to trigger LATS1 degradation. Our findings uncover novel mechanisms through which Gα13 activation induces dysregulation of the Hippo signaling pathway, which leads to aggressive cancer phenotypes, and thereby identify a potential target for preventing the metastatic spread of OvCa.—Yagi, H., Onoyama, I., Asanoma, K., Hori, E., Yasunaga, M., Kodama, K., Kijima, M., Ohgami, T., Kaneki, E., Okugawa, K., Yahata, H., Kato, K. Gα13‐mediated LATS1 down‐regulation contributes to epithelial‐mesenchymal transition in ovarian cancer. FASEB J. 33, 13683‐13694 (2019). www.fasebj.org
The RNA‐binding protein ILF3 binds to transposable element sequences in SINEUP lncRNAs
Authors: Fasolo Francesca , Patrucco Laura , Volpe Massimiliano , Bon Carlotta , Peano Clelia , Mignone Flavio , Carninci Piero , Persichetti Francesca , Santoro Claudio , Zucchelli Silvia , Sblattero Daniele , Sanges Remo , Cotella Diego , Gustincich Stefano
Published: October 2019

Transposable elements (TEs) compose about half of the mammalian genome and, as embedded sequences, up to 40% of long noncoding RNA (lncRNA) transcripts. Embedded TEs may represent functional domains within lncRNAs, providing a structured RNA platform for protein interaction. Here we show the interactome profile of the mouse inverted short interspersed nuclear element (SINE) of subfamily B2 (invSINEB2) alone and embedded in antisense (AS) ubiquitin C‐terminal hydrolase L1 (Uchl1), an lncRNA that is AS to Uchl1 gene. AS Uchl1 is the representative member of a functional class of AS lncRNAs, named SINEUPs, in which the invSINEB2 acts as effector domain (ED)‐enhancing translation of sense protein‐coding mRNAs. By using RNA‐interacting domainome technology, we identify the IL enhancer‐binding factor 3 (ILF3) as a protein partner of AS Uchl1 RNA. We determine that this interaction is mediated by the RNA‐binding motif 2 of ILF3 and the invSINEB2. Furthermore, we show that ILF3 is able to bind a free rightArthrobacter luteus(Alu) monomer sequence, the embedded TE acting as ED in human SINEUPs. Bioinformatic analysis of Encyclopedia of DNA Elements‐enhanced cross‐linking immunoprecipitation data reveals that ILF3 binds transcribed human SINE sequences at transcriptome‐wide levels. We then demonstrate that the embedded TEs modulate AS Uchl1 RNA nuclear localization to an extent moderately influenced by ILF3. This work unveils the existence of a specific interaction between embedded TEs and an RNA‐binding protein, strengthening the model of TEs as functional modules in lncRNAs.—Fasolo, F., Patrucco, L., Volpe, M., Bon, C., Peano, C., Mignone, F., Carninci, P., Persichetti, F., Santoro, C., Zucchelli, S., Sblattero, D., Sanges, R., Cotella, D., Gustincich, S. The RNA‐binding protein ILF3 binds to transposable element sequences in SINEUP lncRNAs. FASEB J. 33, 13572‐13589 (2019).www.fasebj.org
Antifibrinolytic Drugs and Allogeneic Transfusion in Pediatric Multilevel Spine Surgery
Authors: McNeil John , Raphael Jacob , Chow Jonathan H. , Tanaka Kenichi , Mazzeffi Michael A.
Published: October 2019

Study Design.

Observational cohort study with propensity score matching.

Objective.

Determine whether antifibrinolytic drug use is associated with decreased allogeneic blood transfusion in multilevel pediatric spine surgery.

Summary of Background Data.

Antifibrinolytic drugs are commonly used in adult multilevel spine surgery to reduce blood loss and allogeneic transfusion; however, only small studies have examined their efficacy in pediatric patients having multilevel spine surgery.

Methods.

Pediatric patients who had posterior multilevel spine surgery between 2016 and 2017 were identified in the national surgery quality improvement program participant use file. Propensity score matching was used to reduce bias from confounding and the rate of intraoperative allogeneic transfusion was compared between patients who received antifibrinolytic drugs and those who did not. Secondary outcomes included intraoperative cell saver volume, postoperative allogeneic transfusion, massive intraoperative transfusion, and adverse events including venous thromboembolism and seizure.

Results.

A total of 6904 patients underwent posterior multilevel spine surgery during the study period and 83% received antifibrinolytics. The matched cohort included 604 patients. Antifibrinolytic use had no association with reduced intraoperative allogeneic transfusion: odds ratio (OR) = 0.71 (99% confidence interval [CI] = 0.40–1.26, P = 0.12) or cell saver volume, median volume = 114 mL (0, 250 mL) in antifibrinolytic group versus 100 mL (0, 246 mL) in control group, P = 0.04. There was also no association with reduced postoperative allogeneic transfusion OR = 1.23 (99% CI = 0.54–2.81, P = 0.52) or massive transfusion OR = 1.0 (99% CI = 0.34–2.92, P = 1.0). No patient in the matched cohort had a venous thromboembolism or seizure.

Conclusion.

Antifibrinolytic drugs are commonly used in pediatric multilevel spine surgery in the United States, but no efficacy was demonstrated in our study. There were no venous thromboembolisms or seizures implying an excellent safety profile in pediatric patients.

Level of Evidence: 3
Anorectal adenocarcinoma recurrence successfully treated with electrochemotherapy: a case report
Authors: Ferioli Martina , Guido Alessandra , Buwenge Milly , Coe Manuela , Galuppi Andrea , de Terlizzi Francesca , Poggioli Gilberto , Morganti Alessio G.
Published: October 2019

Anal canal adenocarcinoma is generally treated like rectal cancer. Surgery is the standard treatment in early stages and neoadjuvant chemoradiation in locally advanced tumors. Local recurrences treatment paradigm often depends on the previous therapies of either surgery or radiotherapy or systemic therapy. We present the case of a patient with tubulovillous adenocarcinoma of the anal canal which relapsed after chemoradiation. The patient refused salvage surgery and was treated with definitive electrochemotherapy under general anesthesia. Tumor electroporation performed with the insertion of three needles in the recurred site was preceded by an intravenous bolus of bleomycin. After the administered treatment, the patient showed a complete clinical response. A year after electrochemotherapy, the patient is free from local disease with excellent preservation of the sphincter function. Electrochemotherapy may be considered as an alternative to surgery in small lesion in the anorectal region when other approaches are excluded.
Electrosclerotherapy as a Novel Treatment Option for Hypertrophic Capillary Malformations: A Randomized Controlled Pilot Trial
Authors: Horbach Sophie E.R. , Wolkerstorfer Albert , Jolink Folkert , Bloemen Paul R. , van der Horst Chantal M.A.M.
Published: October 2019

BACKGROUND

Bleomycin sclerotherapy is ineffective for treating capillary malformations (CMs) because bleomycin cannot adequately be injected into the small-diameter capillary lumina. Electrosclerotherapy (EST) might be a new treatment modality for CMs, as it combines bleomycin sclerotherapy and “electroporation”—an electric field applied to the tissue. Electroporation disrupts the transmembrane potential, facilitating bleomycin transportation across the vessel wall, hypothetically leading to targeted drug delivery and increased effectiveness of bleomycin in CMs.

OBJECTIVE

To explore the efficacy, safety, and feasibility of EST for CMs in a randomized within-patient controlled pilot study.

MATERIALS AND METHODS

Fifteen regions of interest (ROI) within the hypertrophic CMs of 5 patients were randomly allocated to EST, bleomycin injection, or no treatment. Outcome was assessed after 7 weeks by the patient and a blinded outcome assessor using the patient-observer scar assessment score (POSAS), global assessment of change (GAC), colorimetry, and laser speckle contrast imaging.

RESULTS

Color and hypertrophy of all ROIs treated with EST significantly improved, based on the POSAS (medians patient −11; observer −13), GAC, and colorimetry (ΔE 3.4–16.5) scores.

CONCLUSION

This pilot study demonstrates the first proof of concept for electrosclerotherapy as a new treatment modality for CMs. Further research is warranted.
A case–control study of breast cancer risk and ambient exposure to pesticides
Authors: Tayour Carrie , Ritz Beate , Langholz Bryan , Mills Paul K. , Wu Anna , Wilson John P. , Shahabi Kaveh , Cockburn Myles
Published: October 2019

Background:

While the estrogenic properties of certain pesticides have been established, associations between pesticide exposure and risk of breast cancer have been inconsistently observed. We investigated the relation between pesticide exposure and breast cancer risk using methods capable of objectively assessing exposure to specific pesticides occurring decades before diagnosis.

Methods:

A case–control study was conducted to evaluate the risk of postmenopausal breast cancer associated with historic pesticide exposure in California’s Central Valley, the most agriculturally productive region in the United States where pesticide drift poses a major source of nonoccupational exposure. Residential and occupational histories were linked to commercial pesticide reports and land use data to determine exposure to specific chemicals. Cases (N = 155) were recruited from a population-based cancer registry, and controls (N = 150) were obtained from tax assessor and Medicare list mailings.

Results:

There was no association between breast cancer and exposure to a selected group of organochlorine pesticides thought to have synergistic endocrine-disrupting potential; however, breast cancer was three times as likely to occur among women exposed to chlorpyrifos compared with those not exposed, after adjusting for exposure to other pesticides including organochlorines (OR = 3.22; 95% CI = 1.38, 7.53).

Conclusions:

Organophosphate pesticides, such as chlorpyrifos, have rarely been evaluated in studies of breast cancer risk. Additional research is needed to confirm these findings and to better understand the underlying mechanisms given that chlorpyrifos has been detected in local air monitoring at levels of concern for residents living in the agricultural regions where it is used.
Junctional zone endometrium alterations in gynecological and obstetrical disorders and impact on diagnosis, prognosis and treatment
Authors: Tanos Vasilios , Balami Safinez , Lingwood Lee
Published: October 2019

Purpose of review

To investigate the JZE alterations in gynecological and obstetrical disorders and impact on diagnosis, prognosis and treatment.

Recent findings

JZE was found to be significantly extended in patients with endometriosis, leading to the conclusion that endometriosis is a primary disease of the uterus, much like adenomyosis. Statistical correlation was then demonstrated between the severity of endometriosis and the depth of the adenomyosis infiltrates, hence the thickening of the JZE. Stem cells, predominantly found in the JZE were also found in histological sections of leiomyoma, suggested to be the origin of leiomyoma. This reservoir of JZE stem cells is influenced by different stressors leading to their differentiation into leiomyoma, endometriosis, adenomyosis or endometrial cancer, according to the stressor. The variability in presentation was hypothesized to be connected to genetic and epigenetic factors. JZE was also suggested to act as a barrier, stopping endometrial carcinoma cells invasion and metastasis. In addition, JZE plays a major role in conception, pregnancy and postpartum.

JZE is an important anatomical landmark of the uterus contributing to normal uterine function under the influence of ovarian hormones. Alterations of the JZE thickness and contractility can be used as pathognomonic clinical markers in infertility and chronic pelvic pain, for subendometrial and myometrial disorders, for example, adenomyosis and fibroids. Prospective randomized control trials will clarify the diagnostic steps, imaging modalities to follow and probably triage the patients between medical and surgical treatments.
Volumetric Effect of Pregnancy on a Unilateral Facial Fat Graft
Authors: Tuin A. Jorien , Schepers Rutger H. , Spijkervet Frederik K. L. , Vissink Arjan , Jansma Johan
Published: October 2019

Weight gain can affect the volume of a facial fat graft, resulting in unfavorable asymmetries. Weight gain during pregnancy is more complex and does not just entail an increase in adipose tissue. This case report objectifies whether pregnancy results in volume changes of a facial fat graft. A 24-year-old woman received a fat graft (7 ml) in the mandibular area to mask a volume deficiency. This deficiency occurred after a fibula reconstruction of a mandibular defect resulting from the removal of an ameloblastoma. The patient became pregnant 3 weeks after the fat graft procedure. Standardized 3-dimensional photographs (3dMD) were available preoperatively and at 7 weeks (first trimester), 6 months (second trimester), 9 months (third trimester), and 14 months (4 months after delivery) postoperatively. Three-dimensional analysis revealed that no substantial volume changes of the fat graft occurred during pregnancy other than the overall proportional gain in facial volume. Pregnancy apparently does not affect the volume of a small unilateral fat graft applied in the facial region.
The Paper Mache Bra: A Postsurgical Breast Taping Technique
Authors: Borenstein Amiram , Azaria Ron , Inbar Roy , Friedman Or
Published: October 2019

Little has been published about dressing the breast after surgery and the potential benefits of added support to the routine use of a nonwired bra postoperatively. We report a postsurgical breast taping method and suggest its use might help reduce minor postsurgical complications and subsequent impaired scarring.
Assessment of Rhinoplasty Outcomes with FACE-Q Rhinoplasty Module: Norwegian Linguistic Validation and Clinical Application in 243 Patients
Authors: Kalaaji Amin , Dreyer Stine , Schnegg Jakob , Sanosyan Lena , Radovic Tatjana , Maric Ivana
Published: October 2019

Background:

Patient satisfaction after rhinoplasty is a growing area of research. The FACE-Q Rhinoplasty Module, used to assess these values, requires translation to national languages.

Methods:

Fourteen questions assessing the Satisfaction with Nose Scale and Adverse Effects Checklist of FACE-Q Rhinoplasty Module were translated to Norwegian with adherence to the Mapi Research Trust guidelines. Answers were processed by QuestBack anonymously. Of the 243 patients undergoing rhinoplasty at Oslo Plastic Surgery Clinic, 214 patients were reachable by e-mail.

Results:

Response rates to the pre- and postoperative questionnaire were 23% and 32%, respectively. Responses for somewhat or very satisfied with the nose (pre- versus postoperative) were: overall size of the nose (16.3% versus 61.7%); how straight the nose looks (22.4% versus. 58.3%); how well the nose suits the face (12.2% versus 60%); length of the nose (20.4% versus 68.4%); width of the nose at the bottom (26.6% versus 55%); bridge of the nose (14.3% versus 55%); how the nose looks in photographs (10.2% versus 50%), and tip of the nose (16.3% versus 48.3%). Adverse effects (pre- versus postoperative) were moderate or extreme difficulty breathing through the nose (28.6% versus 35%); tenderness (6.1% versus 23.7%); skin of the nose looking thick or swollen (14.6% versus 30.5%); and unnatural bumps or hollows on the nose (55.1% versus 53.3%).

Conclusions:

Satisfaction levels in rhinoplasty patients are not as high as in other cosmetic surgery procedures, such as breast augmentation. However, compared with baseline, satisfaction levels showed great improvement postoperatively. The Rhinoplasty Module seems useful in evaluating outcome of rhinoplasty. We encourage application of this clinical outcome of rhinoplasty in and among centers.
Scanning Electron Microscopic Features of the Canalicular Entrance Into the Lacrimal Sac
Authors: Ali Mohammad Javed
Published: October 2019

Detailed anatomical features of the common canalicular opening into the lacrimal sac can help our understanding of the focal anatomy and tear rheology.

Purpose:

The aim of this study was to examine the ultrastructural features of the canalicular entrance into the lacrimal sac.

Methods:

Ten openings of the common canaliculus into the lacrimal sac from 10 lacrimal sacs obtained during a dacryocystectomy were studied. Each of the openings were completely excised with 3–4 mm margins on all sides and transported to the laboratory in 2.5% glutaraldehyde. The analysis was performed using the standard protocols of scanning electron microscopy (SEM). The openings, their edges, canalicular lacrimal sac-mucosal folds, and internal surfaces were studied.

Results:

Of the 10 common canalicular openings studied, the upper and lower canaliculi opened into a common canaliculus in all the cases. The terminal portion of the 2 canaliculi had a common wall, which appeared like a septum, just proximal to the beginning of the dilated common canalicular portion. In 60% (6/10) of the cases, a diverticular or a type III sinus of Maier (SOM) was noted. The surface of this diverticulum was smooth and lined by stratified columnar epithelium, reflecting its lacrimal sac origins. Interestingly, the junction of the epithelial change from stratified squamous to columnar could be appreciated clearly in 80% (8/10) of the cases and was mostly located just within from the edge of the internal common opening (ICO). The canalicular lacrimal sac-mucosal folds could be appreciated in 70% (7/10) samples, being very defined and prominent in 30% (3/10).

Conclusions:

The common merged wall of the 2 canaliculus is the most proximal and prominent structure noted on an end-on view of the ICO. Diverticular variant of the sinus of Maier is common. The junction of the epithelial change from stratified squamous to columnar is appreciated just within the edge of the ICO.