bluuebunny/crossref_metadata_2025 huggingface dataset:
P0044THE BIOLOGICAL AND FUNCTIONAL CHARACTERISATION OF GENES RESPONSIBLE FOR MONOGENIC DISORDERS OF THE KIDNEY
Authors: Salehi Mahan , Jiang Xiao , Xu Xiaoguang , Eales James , Tomaszewski Maciej
Published: June 2020

Background and Aims

Single mutations in over 620 genes are known as drivers of approximately 330 monogenic disorders of the kidney. These disorders are estimated to account for up to 10% of chronic kidney disease cases. Due to their disease-causing nature, these genes are particularly clinically relevant targets for molecular analysis, but, so far, there has been no systematic analysis of their expression profile and biological functions in the human kidney. We aimed to characterise and compare the genes responsible for monogenic disorders of the kidney with other non-monogenic protein-coding genes.

Method

We used RNA-sequencing profile of 430 kidneys to explore the characteristics of 530 monogenic genes whose expression was available for analysis in the dataset. The property of genes was characterised using in silico databases such as Genome Reference Consortium Human Build 37 (GRCh37), Drug Gene Interaction database (DGIdb) and the Human Protein Atlas (HPA). The PANTHER (protein analysis through evolutionary relationships) database was used to determine the biological network of interactions between the monogenic genes. A Fast Gene Set Enrichment Analysis (FGSEA) was carried out using single-cell RNA-sequencing data for eight cell types of the kidney from Young et al. Finally, we carried out a two-stage mendelian randomisation to discover a causal link between gene expression and estimated glomerular filtration rate (eGFR) and blood pressure (BP). We used the summary statistics from UK Biobank and the CKDGen consortium for BP and eGFR respectively.

Results

The expression of monogenic genes was both higher and more specific to the kidney, than other protein-coding kidney genes. The pathway analysis found both fetal and organ development to be overrepresented in this set of genes, when compared to non-monogenic kidney genes. We also found that monogenic genes are significantly overrepresented for cell-type specific expression in the proximal tubule and underrepresented in podocytes. Our Mendelian randomisation analysis identified a causal effect between the expression of 50 monogenic genes and either eGFR, systolic or diastolic blood pressure.

Conclusion

Our studies revealed differences in the renal expression profile of monogenic genes and protein-coding genes. The proximal tubule segment of the nephron is a particularly enriched segment of the nephron for monogenic disorders. Kidney expression of 50 of the monogenic genes is causally related to changes in eGFR and blood pressure in the general population.
P0178COMPARATIVE EFFECTIVENESS OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS AND CALCIUM CHANNEL BLOCKERS IN INDIVIDUALS WITH ADVANCED CHRONIC KIDNEY DISEASE: A NATIONWIDE COHORT STUDY
Authors: Fu Edouard L , Clase Catherine M , Evans Marie , Lindholm Bengt , Rotmans Joris , Van Diepen Merel , Dekker Friedo W , Carrero Juan Jesus
Published: June 2020

Background and Aims

There is a lack of data that could help to guide the choice of antihypertensive agents in patients with advanced chronic kidney disease (CKD). We evaluated whether initiating treatment with a renin-angiotensin system inhibitor (RASi) is superior to calcium channel blockers (CCB) in preventing mortality, major adverse cardiovascular events (MACE) or kidney replacement therapy (KRT) in patients with advanced CKD.

Method

Observational study from the Swedish Renal Register, 2007-2017. We identified all nephrologist-referred patients in Sweden who initiated RASi or CCB treatment and had non-dialysis dependent advanced CKD (eGFR <30 ml/min/1.73m2). The associations between RASi vs CCB initiation, mortality, MACE and KRT were assessed by Cox regression. Analyses were adjusted with propensity score weighting for a wide range of confounders, including demographics, blood pressure, laboratory measures, comorbidities and medications. As a positive control we evaluated new use of the same drugs in patients with CKD G3 (N = 2608; eGFR between 30-60 ml/min/1.73m2). Furthermore subgroup, as-treated and competing risk analyses were performed.

Results

The propensity-score weighted cohort included 2479 RASi and 2327 CCB initiators who were well-matched for baseline confounders (all standardized differences <0.1). Median follow-up was 4.1 years, with a maximum follow-up of over 10 years. Compared to CCB, initiation of RASi was associated with a similar risk of mortality (adjusted HR 0.94; 95% CI 0.85-1.03) and MACE (0.99; 0.87-1.13), but with a lower risk of KRT (0.87; 0.78-0.98). Results were consistent across subgroups, in as-treated analyses and after accounting for the competing risk of death. In the control cohort of patients with CKD G3, initiation of RASi (versus CCB) was associated with lower KRT risk (adjusted HR 0.67; 0.47-0.96), and similar risk of mortality (0.91; 0.76-1.08) and MACE (1.06; 0.82-1.35).

Conclusion

Compared with CCB, initiation of RASi in patients with advanced CKD was associated with a lower risk of KRT, but no different risk of mortality or MACE.
P0339URINE METABOLOMIC ASSAY IN EARLY IGA NEPHROPATHY PATIENTS REVEALS URINE GLYCINE AS A PROGNOSTIC BIOMARKER
Authors: Park Sehoon , Yang Seung Hee , Joo Kwon Wook , Kim Jung-Hyun , Kim Dong Ki
Published: June 2020

Background and Aims

A urine metabolomic biomarker from early immunoglobulin A nephropathy (IgAN) can be a useful tool for early detection or prognostic prediction of the disease.

Method

We profiled the urine metabolomes, using nuclear magnetic resonance (NMR) spectrometry, from 197 IgAN patients with eGFR ≥ 60 mL/min/1.73 m2, and the patients with same kidney function range but have diagnosis of membranous nephropathy (n=81) and minimal change disease (n=50) were included as the disease-control group. Additional 146 healthy controls who received routine health screenings and donated urine samples were included. We calculated the creatinine-adjusted urine concentrations of 27 urine metabolites. Urine metabolites specifically increased in urines from IgAN patients were identified, and their associations with the prognosis of the disease, determined with the outcome of eGFR 30% reduction from baseline, were investigated. Additional kidney biopsy samples from independent patients and controls were stained for molecules included in related biological process for experimental validation.

Results

Among the 15 metabolites higher in the urines from IgAN patients than those from the healthy controls, only glycine was the metabolite that the median level was significantly higher also than that of the disease-control group. We found that the higher levels of glycine, alanine, citrate, threonine, and valine were significantly associated with higher risks of 30% eGFR reduction in IgAN patients. Among the molecules related to metabolism of glycine, expressions of T and H proteins from glycine cleavage system were significantly reduced in the kidney biopsy slides from independent IgAN patients when compared to the controls.

Conclusion

Urine glycine may be a prognostic and pathophysiology-related biomarker of IgAN. A further study confirming the clinical usefulness and pathophysiologic significance of urine metabolites in IgAN patients is warranted.
P0969PARKIN INHIBITS THE PROGRESSION OF DIABETIC NEPHROPATHY BY PROMOTING GATA4 DEGRADATION TO REDUCE THE SENESCENCE OF RENAL TUBULAR CELLS
Authors: Chen Kehong , Chen Jia , He Yani
Published: June 2020

Background and Aims

Diabetic nephropathy (DN) can cause end-stage renal disease. During the progression of DN, hyperglycemia accelerates the senescence of renal tubular epithelial cells (RTECs), leading to the tubulointerstitial inflammation and fibrosis. E3-ubiquitin ligase Parkin can regulate several pathophysiological processes. This study explored the role and mechanisms of Parkin in the progression of diabetic nephropathy (DN).

Method

149 cases of patients with DN diagnosed by renal biopsy were recruited in our study. 32 normal kidney samples were obtained from renal carcinoma as control. Renal Parkin expression was detected by immunohistochemistry. The correlation between Parkin expression and renal pathological injury scores, renal function injury parameters were analyzed. In vivo, we generated Parkin overexpressed streptozotocin-induced DN mice using ultrasound- mediated adenovirus transfection. In vitro, knockdown and overexpression experiments were performed by parkin siRNA or Parkin overexpressed adenovirus in high glucose (HG) stimulated mouse primary RTEC. Moreover, we used co-immunoprecipitation and pull down experiments to evaluate the interaction of GATA4 with parkin.

Results

We found that Parkin expression gradually decreased and was inversely associated with IL-6, TGF-β1 and GATA4 expression in the kidney during the progression of DN. Parkin over-expression (OE) reduced inflammation, fibrosis, premature senescence of RTECs and improved renal function while Parkin knockout (KO) had opposite effects in DN mice. Parkin-OE decreased GATA4 protein, but not its mRNA transcripts in the kidney of DN mice and high glucose (HG)-treated RTECs. Immunoprecipitation indicated that Parkin directly interacted with GATA4 in DN kidney. Parkin-OE enhanced GATA4 ubiquitination. Furthermore, Parkin-KO up-regulated growth arrest specific gene 1 (GAS1) expression in renal tubular tissues of DN mice and GATA4-OE enhanced the HG-up-regulated GAS1 expression in RTECs. Conversely, GAS1-OE mitigated the effect of Parkin-OE on HG-induced P21, IL-6 and TGF-β1 expression in RTECs. These results indicate that Parkin inhibits the progression of DN by promoting GATA4 ubiquitination and downregulating the GATA4/GAS1 signaling to inhibit premature senescence, inflammation and fibrosis in DN mice. Thus, these findings uncover new mechanisms underlying the action of Parkin during the process of DN.

Conclusion

Parkin inhibited the progression of DN by promoting GATA4 ubiquitination and downregulating the GATA4/GAS1 signaling to inhibit premature senescence, inflammation and fibrosis. Our findings uncover a novel endogenous protective mechanism by which Parkin regulates the senescence of RTECs, inflammation and fibrosis during the pathogenesis of DN.
P1800RITUXIMAB ENHANCES THE EXPRESSION OF INTERLEUKIN-6 VIA TOLL-LIKE RECEPTOR 3 SIGNALING IN HUMAN PODOCYTE
Authors: Watanabe Shojiro , Hirono Koji , Aizawa Tomomi , Tsugawa Koji , Tanaka Hiroshi
Published: June 2020

Background and Aims

The etiology of idiopathic nephrotic syndrome (INS) in children remains unclear, but it is well known that viral infections often cause relapses of INS. Since toll-like receptor 3 (TLR3), a ligand of viral dsRNA exists in podocytes, dysregulation of TLR3 signaling in podocytes may be involved in the pathogenesis of INS. Recently, rituximab (RTX) a specific antibody to human CD20, has been successfully used to treat children with intractable nephrotic syndrome (frequent relapse nephrotic syndrome, FRNS, and steroid dependent nephrotic syndrome, SDNS). It has been reported that depletion of B cell is main mechanism of RTX treatment. However, some patients experienced recurrence before peripheral blood B cell recovery, whereas selected patients have sustained remission even after peripheral blood B cell recovery. Considering that dramatic effects of RTX in the treatment of INS, it is speculated that some B cell-independent mechanisms of RTX exist. In this context, some recent studies have reported a direct effect of RTX on podocyte, targeting sphingomyelinase phosphodiesterase acid-like 3b (SMPDL3b), but detailed mechanisms remain to be determined. In this study, we examined whether RTX influences TLR3 signaling in cultured human podocyte.

Method

Immortalized human podocytes in culture were treated with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of viral dsRNA. RTX were added before or after the treatment of poly IC. Then, expression of interleukin (IL)-6 were measured using real time RT-PCR and ELISA. Direct binding of RTX to podocyte were confirmed by immunofluorescence.

Results

Poly IC induced the expression of IL-6 in cultured human podocyte in a concentration and time-dependent manner. IL-6 expression induced by poly IC were enhanced in both mRNA and protein level by pretreatment of RTX. RTX itself were apparently stained on podocyte by immunofluorescence.

Conclusion

RTX binds directly to cultured human podocyte and enhances the IL-6 expression induced by poly IC. Since IL-6 from podocyte was reported to be engaged in regulating glomerular inflammation by cross-talk with endothelial cells, exploring the role of enhanced IL-6 from podocyte by RTX, at least in a part, suggests a direct mechanism of RTX in treating intractable nephrotic syndrome in children.
P1838THE CONTRIBUTION OF MICROSCOPE IN THE KNOWLEDGE OF KIDNEY DISEASES AS DESCRIBED BY GIULIO BIZZOZERO
Authors: Bellinghieri Guido , Gembillo Guido , Savica Vincenzo , Satta Ersilia , Salvo Antonino , Santoro Domenico
Published: June 2020

Background and Aims

Giulio Bizzozero (20 March 1846 - 8 April 1901) was an eminent Italian scientist, the father of the modern microscopy. In 1879 he published his masterpiece “Manuale di Microscopia Clinica “(Handbook of Clinical Microscopy). Here he underlined how the microscopic examination of the urine gave to the physicians of the time indicative criteria of alteration of the kidney, often essential for diagnosis.

Method

Bizzozero operates in his book a detailed analysis of the methods of time, laying the foundations of microscopy and diagnosis of renal diseases. He proposed a classification of pathological urine and gave large space to the role of the presence of red blood as a great diagnostic sign in urinary sediment (Figure 1 and Figure 2).

The author emphasized the use of microscopy against the obsoleted vision of old academics and promulgated the experimental methods in opposition to the vitalistic philosophy of the time. Bizzozero underlined the idea of “teamwork” and the strong connection with his close collaborators, he says that on a laboratory “a mind should give the idea and the direction of work while other minds join together dealing with particular executions”.

Results

Bizzozero's revolutionary vision of medicine had the purpose to allow every scientist to reach new discoveries in their field, previously being the privilege of an elite, making him a model both as a doctor as a humanist. In one of his memorable speeches he declared: “We need to undress the science of the cloak of mystery and authority: the professor in the school must not offer a series of dogmas supported by the prestige of his name, he must instead expose science in the real state in which it is found, with its doubts and its unresolved mysteries”.

Conclusion

This Bizzozero’s masterpiece definitely represents a milestone of scientific literature, a witness of the radical evolution of modern medicine and experimental research.
Olfactory Dysfunction in Coronavirus Disease 2019 Patients: Observational Cohort Study and Systematic Review
Authors: Chung Tom Wai-Hin , Sridhar Siddharth , Zhang Anna Jinxia , Chan Kwok-Hung , Li Hang-Long , Wong Fergus Kai-Chuen , Ng Ming-Yen , Tsang Raymond King-Yin , Lee Andrew Chak-Yiu , Fan Zhimeng , Ho Ronnie Siu-Lun , Luk Shiobhon Yiu , Kan Wai-Kuen , Lam Sonia Hiu-Yin , Wu Alan Ka-Lun , Leung Sau-Man , Chan Wai-Ming , Ng Pauline Yeung , To Kelvin Kai-Wang , Cheng Vincent Chi-Chung , Lung Kwok-Cheung , Hung Ivan Fan-Ngai , Yuen Kwok-Yung
Published: June 2020

Background

Olfactory dysfunction (OD) has been reported in coronavirus disease 2019 (COVID-19). However, there are knowledge gaps about the severity, prevalence, etiology, and duration of OD in COVID-19 patients.

Methods

Olfactory function was assessed in all participants using questionnaires and the butanol threshold test (BTT). Patients with COVID-19 and abnormal olfaction were further evaluated using the smell identification test (SIT), sinus imaging, and nasoendoscopy. Selected patients received nasal biopsies. Systematic review was performed according to PRISMA guidelines. PubMed items from January 1, 2020 to April 23, 2020 were searched. Studies that reported clinical data on olfactory disturbances in COVID-19 patients were analyzed.

Results

We included 18 COVID-19 patients and 18 controls. Among COVID-19 patients, 12 of 18 (67%) reported olfactory symptoms and OD was confirmed in 6 patients by BTT and SIT. Olfactory dysfunction was the only symptom in 2 patients. Mean BTT score of patients was worse than controls (P = .004, difference in means = 1.8; 95% confidence interval, 0.6–2.9). Sinusitis and olfactory cleft obstruction were absent in most patients. Immunohistochemical analysis of nasal biopsy revealed the presence of infiltrative CD68+ macrophages harboring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen in the stroma. Olfactory dysfunction persisted in 2 patients despite clinical recovery. Systematic review showed that the prevalence of olfactory disturbances in COVID-19 ranged from 5% to 98%. Most studies did not assess olfaction quantitatively.

Conclusions

Olfactory dysfunction is common in COVID-19 and may be the only symptom. Coronavirus disease 2019-related OD can be severe and prolonged. Mucosal infiltration by CD68+ macrophages expressing SARS-CoV-2 viral antigen may contribute to COVID-19-related OD.
Vibrio fluvialis Liver Abscess and Bacteremia in a Sashimi Lover: A Case Report and Review of the Literature
Authors: Kitaura Satoshi , Okamoto Koh , Wakabayashi Yoshitaka , Okada Yuta , Okazaki Aiko , Ikeda Mahoko , Hakuta Ryunosuke , Nakai Yousuke , Okugawa Shu , Koike Kazuhiko , Moriya Kyoji
Published: June 2020

Vibrio fluvialis is a foodborne pathogen known to cause a cholera-like gastroenteritis syndrome. Here we report the first case of V. fluvialis liver abscess and bacteremia presumed to be from sashimi, a Japanese raw seafood delicacy. We also provide a literature review of reported cases of V. fluvialis extra-intestinal diseases including bacteremia.
Inappropriate Antibiotic Prescribing for Respiratory Conditions Does Not Improve Press Ganey Patient Satisfaction Scores in the Emergency Department
Authors: Pulia Michael S , Hesse Steven , Schwei Rebecca J , Schulz Lucas T , Sethi Ajay , Hamedani Azita
Published: June 2020

Background

The literature has mixed results regarding the relationship between antibiotic prescribing and patient satisfaction in the emergency department (ED) for antibiotic-inappropriate respiratory diagnoses. The objective of the study was to determine if ED patients who receive nonindicated antibiotic prescriptions for respiratory tract conditions have increased Press Ganey patient satisfaction scores compared with those who do not receive antibiotics.

Methods

This was a retrospective observational study. Using an administrative electronic health record data set from 2 EDs in the Midwest, we identified 619 ED encounters resulting in discharge for antibiotic-inappropriate respiratory diagnoses with a corresponding Press Ganey patient satisfaction survey. We compared sociodemographics, encounter variables, and overall Press Ganey patient satisfaction scores between those who did and did not receive antibiotics. We analyzed Press Ganey scores by categorical score distribution and as a dichotomized scale of top box (5) vs other scores. A logistic regression estimated the odds of a top box Press Ganey patient satisfaction score based on antibiotic prescribing while controlling for other covariates.

Results

In the final sample, 158 (26%) encounters involving antibiotic-inappropriate respiratory diagnoses involved an antibiotic prescription. There were no differences in sociodemographic, encounter or categorical, or top box Press Ganey overall patient satisfaction scores between the groups that did and did not receive inappropriate antibiotics. In the fully adjusted regression model, antibiotic prescriptions were not associated with increased odds of top box Press Ganey patient satisfaction score (odds ratio, 0.78; 95% CI, 0.53–1.14).

Conclusions

Our findings suggest that nonindicated antibiotic prescribing for respiratory tract conditions is not a primary driver of overall Press Ganey scores in the ED.
Longitudinal Pharmacokinetic-Pharmacodynamic Biomarkers Correlate With Treatment Outcome in Drug-Sensitive Pulmonary Tuberculosis: A Population Pharmacokinetic-Pharmacodynamic Analysis
Authors: Kloprogge Frank , Mwandumba Henry C , Banda Gertrude , Kamdolozi Mercy , Shani Doris , Corbett Elizabeth L , Kontogianni Nadia , Ward Steve , Khoo Saye H , Davies Geraint R , Sloan Derek J
Published: June 2020

Background

This study aims to explore relationships between baseline demographic covariates, plasma antibiotic exposure, sputum bacillary load, and clinical outcome data to help improve future tuberculosis (TB) treatment response predictions.

Methods

Data were available from a longitudinal cohort study in Malawian drug-sensitive TB patients on standard therapy, including steady-state plasma antibiotic exposure (154 patients), sputum bacillary load (102 patients), final outcome (95 patients), and clinical details. Population pharmacokinetic and pharmacokinetic-pharmacodynamic models were developed in the software package NONMEM. Outcome data were analyzed using univariate logistic regression and Cox proportional hazard models in R, a free software for statistical computing.

Results

Higher isoniazid exposure correlated with increased bacillary killing in sputum (P < .01). Bacillary killing in sputum remained fast, with later progression to biphasic decline, in patients with higher rifampicin area under the curve (AUC)0-24 (P < .01). Serial sputum colony counting negativity at month 2 (P < .05), isoniazid CMAX (P < .05), isoniazid CMAX/minimum inhibitory concentration ([MIC] P < .01), and isoniazid AUC0-24/MIC (P < .01) correlated with treatment success but not with remaining free of TB. Slower bacillary killing (P < .05) and earlier progression to biphasic bacillary decline (P < .01) both correlate with treatment failure. Posttreatment recurrence only correlated with slower bacillary killing (P < .05).

Conclusions

Patterns of early bacillary clearance matter. Static measurements such as month 2 sputum conversion and pharmacokinetic parameters such as CMAX/MIC and AUC0-24/MIC were predictive of treatment failure, but modeling of quantitative longitudinal data was required to assess the risk of recurrence. Pooled individual patient data analyses from larger datasets are needed to confirm these findings.
Countermeasures to Coronavirus Disease 2019: Are Immunomodulators Rational Treatment Options—A Critical Review of the Evidence
Authors: Chastain Daniel B , Stitt Tia M , Ly Phong T , Henao-Martínez Andrés F , Franco-Paredes Carlos , Osae Sharmon P
Published: June 2020

Severe acute respiratory syndrome coronavirus 2 is associated with higher concentrations of proinflammatory cytokines that lead to lung damage, respiratory failure, and resultant increased mortality. Immunomodulatory therapy has the potential to inhibit cytokines and quell the immune dysregulation. Controversial data found improved oxygenation after treatment with tocilizumab, an interleukin-6 inhibitor, sparking a wave of interest and resultant clinical trials evaluating immunomodulatory therapies. The purpose of this article is to assess potential proinflammatory targets and review the safety and efficacy of immunomodulatory therapies in managing patients with acute respiratory distress syndrome associated with coronavirus disease 2019.
Factors Associated With Testing for Hepatitis C Infections Among a Commercially Insured Population of Persons With HIV, United States 2008–2016
Authors: King Hope , Bull–Otterson Lara , Hoover Karen W , Huang Huang Ya-Lin A , Zhu Weiming , Thompson William
Published: June 2020

Background

Hepatitis C virus (HCV) infection is an important public health problem among people with HIV. People with HIV who are coinfected with HCV infection are at increased risk for cirrhosis, liver failure, and hepatitis C–related mortality; as such, national guidelines recommend that persons with HIV be tested for HCV infection.

Methods

Data from the 2003–2017 IBM Watson Health MarketScan database were used for this study. We used diagnostic, procedural, and drug codes to identify patients with ≥1 inpatient or outpatient medical claim of HIV diagnosis. Patients with prior HIV or hepatitis C diagnoses were excluded. We calculated hepatitis C testing rates among newly diagnosed HIV-infected persons within 12 months of the initial HIV diagnosis date (January 1, 2008–December 31, 2016). We used Poisson regression to identify the factors associated with hepatitis C testing. Lastly, we assessed hepatitis C testing trends using the Cochran-Armitage test.

Results

The prevalence of testing for hepatitis C in newly identified persons with HIV (n = 46 277) was 50% within 12 months of the index HIV diagnosis. From 2008 to 2017, the testing rate increased by 13%. Significant predictors of hepatitis C testing were age, sex, and urbanicity. Women with HIV were less likely to have been tested compared with men (relative risk, 0.79; 95% CI, 0.77–0.81). Only 40% of patients between 50 and 59 years of age were tested for hepatitis C within 12 months of the index HIV diagnosis, while 56% of persons with HIV aged 20–29 years were tested for hepatitis C.

Conclusions

Overall, 50% of newly diagnosed HIV patients were tested for hepatitis C within 12 months of HIV diagnosis. Although there were increases in hepatitis C testing rates over the study period, there were missed opportunities to detect HCV infection among people newly diagnosed with HIV.
Selective Posterior Callosotomy for Treatment of Epileptic Drop Attacks: Video Documentation of the Surgical Technique: 2-Dimensional Operative Video
Authors: Marchiori Maurício , Palmini André , Martins William Alves , Paglioli Rafael Silva , Frigeri Thomas Moré , Paglioli Eliseu
Published: June 2020

This is a surgical technique video of selective posterior callosotomy (SPC), a novel surgical procedure to alleviate refractory epileptic drop attacks.
1
Departing from traditional approaches aiming the anterior half or the entire callosum, SPC sections the posterior half of the callosum sparing prefrontal connectivity.
1
Drop attacks are generalized epileptic seizures characterized by sudden falls.
1
These seizures are often seen in diffuse brain pathology associated with generalized or multifocal epilepsies, whose electroencephalogram (EEG) “fingerprint” is bilaterally synchronous epileptic discharges.
1
Sectioning the callosum to control drop attacks follows the rationale that the rapid synchronization of discharges between motor and premotor regions of both hemispheres is the basis.
1
The standard approach to callosotomies always contemplated the anterior fibers of the callosum.
2
Literature reports that anterior sections lead to unsatisfactory control of drop attacks, and results are improved when extended into a total callosotomy.
2,3
This evidence coupled with diffusion tensor imaging (DTI) findings showing that motor and premotor fibers actually cross through posterior half of the callosum led us to hypothesize that selective section of the posterior half of the callosum would section all relevant motor fibers and control drop attacks to a similar extent to total callosotomies, with the advantage of sparing prefrontal interconnectivity
3
and no split-brain syndrome. Both our series, one retrospective, followed by a new prospective study have confirmed SPC to be a safe procedure, leading to complete or greater than 90% control of epileptic falls in 85% of patients.
1
The video presented here was recorded during a selective posterior callosotomy performed on a 13-yr-old girl who had hundreds of uncontrollable drop attacks per day. Falls were completely controlled with significant gains in psychomotor development and cognition, after 5 yr of follow-up. The patient provided signed consent to the surgical procedure, video acquisition, photo acquisition, and storage at operations, and the publication of this material.
Pseudoaneurysm of the Superficial Temporal Artery After Intracranial Pressure Monitoring Device Placement: Case Report of a Rare Complication
Authors: Pan James , Barros Guilherme , Greil Madeline E , Meyer R Michael , Ene Chibawanye I , Chesnut Randall M
Published: June 2020

BACKGROUND AND IMPORTANCE

Pseudoaneurysms involving the superficial temporal artery (STA), either iatrogenic or caused by direct trauma, are rare. The STA is prone to injury due to its long course throughout the scalp. Injuries can cause cosmetic defects and/or skin breakdown leading to further complications.

CLINICAL PRESENTATION

We report a case of delayed iatrogenic pseudoaneurysm of the STA after placement of an intracranial pressure monitor in the setting of acute traumatic brain injury. The patient had a delayed development of a pulsatile mass over his right frontal region, with computed tomography angiography concerning for a pseudoaneurysm of the STA. This was managed with surgical resection with complete resolution of symptoms at follow-up.

CONCLUSION

We review the literature regarding the etiology, pathogenesis, and management of these lesions. While iatrogenic injuries to the STA have been previously reported, this is a curious case related to placement of an intracranial pressure monitor. We recommend direct surgical resection of the pseudoaneurysm for cosmetic effect and prevention of further wound breakdown.
Quad S2-Alar-Iliac Screw Fixation via Navigated Spinal Robotics With Software Planning: 2-Dimensional Operative Video
Authors: Pham Martin H , Diaz-Aguilar Luis Daniel , King Bradley H , Osorio Joseph A , Lehman Ronald A
Published: June 2020

The use of robotic guidance for spinal instrumentation has become promising for its ability to offer the advantages of precision, accuracy, and reproducibility. However, utilization and adoption of robotic platforms for spine surgery remain limited especially in comparison to other surgical fields. We present here a case of a 71-yr-old man with a prior T4-pelvis long-segment fusion who presented with distal sacro-iliac instrumentation loosening with pseudarthrosis. He subsequently underwent construct revision with quad (bilateral dual) S2-alar-iliac screw fixation with navigated spinal robotic assistance (Mazor X Stealth Edition, Medtronic Sofamor Danek, Medtronic Inc, Dublin, Ireland). To our knowledge, this is the first video demonstrating the preoperative software planning and intraoperative workflow for placing quad S2-alar-iliac screws with navigated spinal robotic guidance using the Mazor X Stealth Edition.

 There is no identifying information in this video. Patient consent was obtained for the surgical procedure and for publishing of the material included in the video.
Decrease in diatom dominance at lower Si:N ratios alters plankton food webs
Authors: Makareviciute-Fichtner Kriste , Matthiessen Birte , Lotze Heike K , Sommer Ulrich
Published: June 2020

Many coastal oceans experience not only increased loads of nutrients but also changes in the stoichiometry of nutrient supply. Excess supply of nitrogen and stable or decreased supply of silicon lower silicon to nitrogen (Si:N) ratios, which may decrease diatom proportion in phytoplankton. To examine how Si:N ratios affect plankton community composition and food web structure, we performed a mesocosm experiment where we manipulated Si:N ratios and copepod abundance in a Baltic Sea plankton community. In high Si:N treatments, diatoms dominated. Some of them were likely spared from grazing unexpectedly resulting in higher diatom biomass under high copepod grazing. With declining Si:N ratios, dinoflagellates became more abundant under low and picoplankton under high copepod grazing. This altered plankton food web structure: under high Si:N ratios, edible diatoms were directly accessible food for copepods, while under low Si:N ratios, microzooplankton and phago-mixotrophs (mixoplankton) were a more important food source for mesograzers. The response of copepods to changes in the phytoplankton community was complex and copepod density-dependent. We suggest that declining Si:N ratios favor microzoo- and mixoplankton leading to increased complexity of planktonic food webs. Consequences on higher trophic levels will, however, likely be moderated by edibility, nutritional value or toxicity of dominant phytoplankton species.
(Debt) Overhang: Evidence from Resource Extraction
Authors: Wittry Michael D
Published: June 2020

I study the empirical importance of debt overhang using a unique data set on resource extraction firms that provides ex ante measures of investment opportunities and important variation in terms of a firm’s obligations. In particular, unsecured reclamation liabilities create overhang that is costly to resolve and induces firms to forgo and postpone positive NPV investments. Traditional debt, in contrast, imposes few overhang-related investment distortions. These results show that (a) the overhang problem is potentially large and more broadly applies to firms’ nondebt liabilities and (b) overhang problems associated with traditional debt can be avoided through contracting and debt composition.
Black Girls and the Talk? Policing, Parenting, and the Politics of Protection
Authors: Malone Gonzalez Shannon
Published: June 2020

Black girls are marginalized from mainstream discourses and familial discussions on policing, and little is known about how families conceptualize strategies for mitigating their risk of police sexual assault and harassment. Through 30 in-depth interviews with black mothers, this article explores how social class shapes protective care strategies for reducing girls’ risk of police contact and sexual violence. While the primary police talk emphasizes black boys’ vulnerability to lethal and physical violence, I identify two additional socialization practices, or “talks” for black girls: The respectability talk is a middle-class socialization strategy that avoids direct associations between black girls and police; this talk works to minimize risk through teaching black girls how to be “ladies” by embodying racialized gendered norms that constrain their behavior and autonomy. The predatory talk is a predominantly working-class socialization strategy which aims to equip black girls with an awareness of police sexual violence and the tools for avoiding sexual assault and harassment from officers when alone or at night. The article illustrates how protective care strategies for black girls are intertwined with social class and have divergent consequences for understanding agency and responsibility for police sexual violence.
Effect of anabolic hormone exposure during the backgrounding-phase in calf-fed steers of different mature sizes1
Authors: Gentry Wes W , Blom Ethan J , Pritchard Robbi H , Hales Kristin E
Published: June 2020

The mature size (MS) of cows in the United States is diverse, which leads to diversity in the MS of feeder cattle and hot carcass weights (HCW) of fed cattle. Cattle feeders must manage this inherent variation. Given that implants alter MS, they may be an effective tool to manage variation in HCW across groups of cattle. Two experiments were conducted to evaluate the interaction of MS and implant status in calf-fed steers. Steer calves from the same two sources were used in both experiments. Because breeding seasons were <60 d, it was assumed that weaning weight (WW) to a large extent reflected differences in MS. Smaller MS (SMS) and larger MS (LMS) steers were identified from the tails of the WW distribution. Within each MS group, steers were implanted with 20 mg estradiol benzoate and 200 mg progesterone (SS) or 14 mg estradiol benzoate and 100 mg trenbolone acetate (CH) on d 1 (Exp. 1), and nonimplanted (NI) or implanted with SS on d 2 (Exp. 2). In both experiments, a common terminal implant was used and steers were fed for 161 (Exp. 1) and 168 d (Exp. 2). Data were analyzed as a randomized complete block design with a 2 × 2 factorial treatment structure, with main effects of MS and implant. No MS × implant interactions were observed in either experiment (P ≥ 0.08). In both experiments LMS steers had heavier body weights (BW), HCW, and BW adjusted to 28% empty body fat (AFBW), greater average daily gain (ADG), dry matter intake (DMI), and lesser gain:feed (G:F) than SMS steers (P ≤ 0.02). No differences were evident in marbling score or Quality Grade distributions between SMS and LMS steers (P ≥ 0.13). In Exp. 1, no differences in growth performance, carcass traits, AFBW, or calculated frame size (FS) were observed for steers initially implanted with SS or CH (P ≥ 0.12). In Exp. 2, steers implanted initially with SS had heavier final BW, greater ADG and DMI (P ≤ 0.01), and similar G:F (P = 0.78) than NI steers. Steers initially implanted with SS had heavier HCW (P < 0.01), but no other differences in carcass characteristics were observed (P ≥ 0.23). Additionally, steers implanted with SS tended to have heavier AFBW (P = 0.07) and greater calculated FS (P = 0.05) than NI steers. Steers of different MS responded similarly to implants. Previous exposure to implants did not alter the response to the terminal implant. Estradiol increases the FS of steers; however, when similar doses of estradiol are compared, trenbolone acetate did not further increase FS (Exp. 1).
A Positive Feedback Loop Between c-Myc Upregulation, Glycolytic Shift, and Histone Acetylation Enhances Cancer Stem Cell-like Property and Tumorigenicity of Cr(VI)-transformed Cells
Authors: Clementino Marco , Xie Jie , Yang Ping , Li Yunfei , Lin Hsuan-Pei , Fenske William K , Tao Hua , Kondo Kazuya , Yang Chengfeng , Wang Zhishan
Published: June 2020

Chronic hexavalent chromium [Cr(VI)] exposure causes lung cancer and other types of cancer; however, the mechanism of Cr(VI) carcinogenesis remains to be clearly defined. Our recent study showed that chronic Cr(VI) exposure upregulates the proto oncogene c-Myc expression, which contributes significantly to Cr(VI)-induced cell transformation, cancer stem cell (CSC)-like property and tumorigenesis. c-Myc is a master regulator of cancer cell abnormal metabolism and accumulating evidence suggests that metabolism dysregulation plays an important role in both cancer development and progression. However, little is known about the role of metabolism dysregulation in Cr(VI) carcinogenesis. This study was performed to investigate the potential role and mechanism of metabolism dysregulation in Cr(VI) carcinogenesis. It was found that Cr(VI)-transformed cells display glycolytic shift, which depends on the upregulation of c-Myc. The glycolytic shift in Cr(VI)-transformed cells led to increased production of acetyl coenzyme A (acetyl-CoA) and elevation of histone acetylation. This, in turn, upregulated the expression of an acetyl-CoA producing key enzyme ATP citrate lyase and c-Myc, forming a positive feedback loop between the upregulation of c-Myc expression, glycolytic shift and increased histone acetylation. It was further determined that glucose depletion not only reverses the glycolytic shift in Cr(VI)-transformed cells, but also significantly reduces their growth, CSC-like property and tumorigenicity. These findings indicate that glycolytic shift plays an important role in maintaining malignant phenotypes of Cr(VI)-transformed cells, suggesting that metabolism dysregulation is critically involved in Cr(VI) carcinogenesis.
Development and Internal Validation of a Prediction Model for In-Hospital Mortality in Geriatric Patients With a Hip Fracture
Authors: Schuijt Henk Jan , Smeeing Diederik P. J. , Würdemann Franka S. , Hegeman J. Han , Geraghty Olivia C. , Houwert R. Marijn , Weaver Michael J. , van der Velde Detlef ,   on behalf of the Dutch Hip Fracture Audit Taskforce study group
Published: June 2020

Objective:

To develop and validate a prediction model for in-hospital mortality in patients with hip fracture 85 years of age or older undergoing surgery.

Design:

A multicenter prospective cohort study.

Setting:

Six Dutch trauma centers, level 2 and 3.

Participants:

Patients with hip fracture 85 years of age or older undergoing surgery.

Intervention:

Hip fracture surgery.

Main Outcome Measurements:

In-hospital mortality.

Results:

The development cohort consisted of 1014 patients. In-hospital mortality was 4%. Age, male sex, American Society of Anesthesiologists classification, and hemoglobin levels at presentation were independent predictors of in-hospital mortality. The bootstrap adjusted performance showed good discrimination with a c-statistic of 0.77.

Conclusion:

Age, male sex, higher American Society of Anesthesiologists classification, and lower hemoglobin levels at presentation are robust independent predictors of in-hospital mortality in patients with geriatric hip fracture and were incorporated in a simple prediction model with good accuracy and no lack of fit.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Trends in Drug Resistance in Childhood Tuberculosis in Cape Town, South Africa
Authors: Schaaf H. Simon , Garcia-Prats Anthony J. , Draper Heather R. , Rautenbach Corné , Bosch Corné , Demers Anne-Marie , Hesseling Anneke C. , Walters Elisabetta
Published: June 2020

Background:

We determined mycobacterial drug resistance and HIV prevalence among children with bacteriologically confirmed tuberculosis (TB) from March 2013 to February 2017. Results were compared with 5 previous 2-year surveillance studies (2003–2013).

Methods:

Prospective surveillance of all bacteriologically confirmed TB in children (0–13 years) completed at Tygerberg Hospital, Cape Town, South Africa. Drug susceptibility testing was done by GenoType MTBDRplus for isoniazid and rifampicin; ofloxacin and amikacin drug susceptibility testing was completed if rifampicin resistance was detected. Xpert MTB/RIF was routinely introduced during this period.

Results:

Six hundred sixty-two children, median age 34 months (interquartile range 14–79) had bacteriologically confirmed TB; 587 (88.7%) were culture-confirmed and 75 (11.3%) confirmed by Xpert MTB/RIF only. Of culture-confirmed cases, 509 (86.7%) were pan-susceptible, 47 (8.0%) were multidrug-resistant, 13 (2.2%) were RIF-resistant/INH-susceptible and 18 (3.1%) were INH-resistant/RIF-susceptible. Of Xpert-positive cases, 3/75 (4%), 68/75 (92%) and 4/75 (5%) were RIF-resistant, RIF-susceptible and RIF-indeterminate, respectively. Of 573 (97.6%) children tested, 74 (12.9%) were HIV positive. Compared with previous surveillance periods, RIF mono-resistance increased from 0% to 2.2% (trend test: χ2 = 7.050, P = 0.0079). HIV prevalence decreased from 29% to 10.6% (trend test: χ2 = 27.975, P < 0.0001). Of multidrug-resistant cases, 15/47 (32%) were ofloxacin resistant.

Conclusions:

The increase in RIF-resistant/INH-susceptible cases and ofloxacin resistance among multidrug-resistant TB cases in children, indicative of recent transmission, is concerning. The prevalence of multidrug-resistant TB remains high in children.
The Conceptual Structure of the Management by Nurses of the Ego Integrity of Residents of Nursing Homes
Authors: LIM Sun-Young , CHANG Sung Ok
Published: June 2020

Background

The number of older people admitted to nursing homes has continued to rise with the recent expansion of the Republic of Korea's long-term care system. Maintaining ego integrity is a major task for older people approaching the end of life. As efforts to maintain ego integrity include the final stages of life, this concept is critically important for older people in nursing homes. This study was designed to assess issues related to ego integrity in the nursing home environment to determine how nurses should play a key role in managing this important life task.

Purpose

The management by nurses of the ego integrity of residents of nursing homes is a new phenomenon that is central to promoting long-term, quality care. This study was designed to clarify and conceptualize this management phenomenon in the context of nursing homes.

Methods

A hybrid model of concept development was used to analyze the ways in which nurses manage the ego integrity of residents of nursing homes. In the theoretical phase, a working definition of the management by nurses of residents' ego integrity is developed using a literature review. In the fieldwork phase, in-depth interviews are conducted with eight nurses from six nursing homes in Seoul and three other provinces. Finally, in the final analytical phase, the theoretical and fieldwork findings are interpreted and compared.

Results

Two components, assessment and intervention, of the approach by nurses to managing the ego integrity of residents of nursing homes were identified. Assessment incorporates 10 attributes in the following three dimensions: “identifying the extent to which residents' basic needs are being fulfilled,” “determining how residents achieve friendly relationships with others,” and “determining how each resident creates a harmonious view of his or her life.” Intervention incorporates nine attributes in the following two dimensions: “helping residents develop a positive view of life” and “helping residents make the best use of their remaining functional abilities.”

Conclusions/Implications for Practice

By managing the ego integrity of residents, nurses have a significant influence on residents' sociopsychological adaptation, especially in the challenging environment of a nursing home. This study supports that managing the ego integrity of residents of nursing homes is an important and practical component of the role played by nurses and of the aid and care they provide. Furthermore, the findings verify the effectiveness of intervention studies in examining assessment tools and developing guidelines for ego-integrity management.
Extracorporeal Life Support for Cardiogenic Shock With Either a Percutaneous Ventricular Assist Device or an Intra-Aortic Balloon Pump
Authors: Nakajima Tomohiro , Tanaka Yuki , Fischer Irene , Kotkar Kunal , Damiano Ralph J. , Moon Marc R. , Masood Muhammad F. , Itoh Akinobu
Published: June 2020

Extracorporeal life support (ECLS) can result in complications due to increased left ventricular (LV) afterload. The percutaneous ventricular assist device (PVAD) and intra-aortic balloon pump (IABP) are both considered to be effective means of LV unloading. This study describes the efficacy of LV unloading and related outcomes with PVAD or IABP during ECLS. From January 2010 to April 2018, all cardiogenic shock patients who underwent ECLS plus simultaneous PVAD or IABP were analyzed. Forty-nine patients received ECLS + PVAD, while 91 received ECLS + IABP. At 48 hours, mean pulmonary artery pressure was significantly reduced in both groups [34 mm Hg to 22, p < 0.01; 32 mm Hg to 21, p < 0.01; ECLS + PVAD and ECLS + IABP group, respectively]. The two groups had similar 30 day survival rates [19 patients (39%) vs. 35 (39%), p = 0.56]. The ECLS + PVAD group had higher incidences of bleeding at the insertion site [11 (22%) vs. 0, p < 0.01] and major hemolysis [9 (18%) vs. 0, p < 0.01]. Both groups had improvement in LV end-diastolic dimension (61 ± 12 mm to 54 ± 12, p = 0.03; 60 ± 12 mm to 47 ± 10, p < 0.01), and LV ejection fraction (16 ± 7% to 22 ± 10, p < 0.01; 22 ± 12% to 29 ± 15, p = 0.01). Both ECLS + PVAD and ECLS + IABP effectively reduced pulmonary artery pressure and improved LV function. Bleeding at the PVAD or IABP insertion site occurred more frequently in the ECLS + PVAD group than the ECLS + IABP group (p < 0.01). Nine patients (18%) in the ECLS + PVAD group experienced major hemolysis, while there was no hemolysis in the ECLS + IABP group (p < 0.01). Careful considerations are required before selecting an additional support to ECLS.