bluuebunny/crossref_metadata_2025 huggingface dataset:
Patched 1-interacting Peptide Represses Fibrosis in Pancreatic Cancer to Augment the Effectiveness of Immunotherapy
Authors: Oyama Yasuhiro , Onishi Hideya , Koga Satoko , Murahashi Mutsunori , Ichimiya Shu , Nakayama Kazunori , Fujimura Akiko , Kawamoto Makoto , Imaizumi Akira , Umebayashi Masayo , Ohuchida Kenoki , Morisaki Takashi , Nakamura Masafumi
Published: December 2019

Pancreatic ductal adenocarcinoma (PDAC) is resistant to immunotherapy. As a factor of resistance, the dense fibrosis of this cancer acts as a barrier to inhibit immune cell infiltration into a tumor. We examined the influence of a Hedgehog signal inhibitor, Patched 1-interacting peptide, on fibrosis, infiltration of immune cells, and immunotherapeutic effects on PDAC. We found that this peptide inhibited proliferation and migration of cancer-associated fibroblasts and cancer cells. Furthermore, this peptide reduced the production of extracellular matrix and transforming growth factor β1 in cancer-associated fibroblasts and induced expression of HLA-ABC in PDAC cells and interferon-γ in lymphocytes. In vivo, the peptide suppressed fibrosis of PDAC and increased immune cell infiltration into tumors. The combination of this peptide and an anti-programmed death-1 antibody augmented the antitumor effect, and this combination showed the same effect in experiments using cancer cells and autologous lymphocytes. These results indicate that, in addition to the direct effect of tumor suppression, the Patched 1-interacting peptide increases the infiltration of immune cells by reducing fibrosis of PDAC and consequently enhances the effect of immunotherapy. Therefore, treatment with this peptide may be a novel therapy with 2 different mechanisms: direct tumor suppression and enhancing the immune response against PDAC.
Generation of Antitumor T Cells For Adoptive Cell Therapy With Artificial Antigen Presenting Cells
Authors: Shrestha Bishwas , Zhang Yongliang , Yu Bin , Li Gongbo , Boucher Justin C. , Beatty Nolan J. , Tsai Ho-Chien , Wang Xuefeng , Mishra Asmita , Sweet Kendra , Lancet Jeffrey E. , Kelley Linda , Davila Marco L.
Published: December 2019

Adoptive cell therapy with ex vivo expanded tumor infiltrating lymphocytes or gene engineering T cells expressing chimeric antigen receptors (CAR) is a promising treatment for cancer patients. This production utilizes T-cell activation and transduction with activation beads and RetroNectin, respectively. However, the high cost of production is an obstacle for the broad clinical application of novel immunotherapeutic cell products. To facilitate production we refined our approach by using artificial antigen presenting cells (aAPCs) with receptors that ligate CD3, CD28, and the CD137 ligand (CD137L or 41BBL), as well as express the heparin binding domain (HBD), which binds virus for gene-transfer. We have used these aAPC for ex vivo gene engineering and expansion of tumor infiltrating lymphocytes and CAR T cells. We found that aAPCs can support efficacious T-cell expansion and transduction. Moreover, aAPCs expanded T cells exhibit higher production of IFN-γ and lower traits of T-cell exhaustion compared with bead expanded T cells. Our results suggest that aAPC provide a more physiological stimulus for T-cell activation than beads that persistently ligate T cells. The use of a renewable cell line to replace 2 critical reagents (beads and retronectin) for CAR T-cell production can significantly reduce the cost of production and make these therapies more accessible to patients.
Ultralow 0.03 mg vaginal estriol in postmenopausal women who underwent surgical treatment for stress urinary incontinence: effects on quality of life and sexual function
Authors: Caruso Salvatore , Cianci Antonio , Sarpietro Giuseppe , Matarazzo Maria Grazia , Panella Marco , Cianci Stefano
Published: December 2019

Objective:

To evaluate the efficacy of low-dose, intravaginal estriol ovules in postmenopausal women with stress urinary incontinence (SUI) before and after transobturator tape (TOT) placement, assessing vaginal health, quality of life (QoL), and sexual function.

Methods:

Ninety-six postmenopausal women affected by SUI and scheduled for TOT placement were enrolled. Women were randomized and divided into two groups through 1:1 at baseline (T0): study group (group A, n = 48) and control group (group B, n = 48). Group A was treated daily for 16 weeks with an intravaginal ovule containing 0.03 mg estriol. Vaginal epithelium maturation, QoL, and sexual function were investigated by using the Vaginal Maturation Index (VMI), Short Form-36 (SF-36) questionnaire, and Female Sexual Function Index (FSFI) questionnaire at baseline (T0), before surgery (T1), and 8 weeks after surgery (T2), respectively.

Results:

Thirty-six women from group A and 44 women from group B completed the study. The VMI improved in group A at T1 (T1 [43.1] vs T0 [38.1]; P = 0.04) and T2 (T2 [47.8] vs T0 [38.1]; P = 0.001). The physical index score of the QoL improved only after surgery in group A (T2 [49.4] vs T0 [39.7]; P = 0.001). On the contrary, the mental index score improved at T1 [T1 (41.9) vs T0 (37.9), (P = 0.02)] and at T2 [T2 (49.6) vs T0 (37.9), P = 0.001]. Group B had improvement of the physical (45.6 vs 39.4; P = 0.001) and mental (43.6 vs 38.9; P = 0.002) index scores at T2. Sexual function improved in group A at T1 (13.9 vs 18.6; P = 0.001) and at T2 (13.9 vs 25.2; P = 0.001), and in group B at T2 (14 vs 17.2; P = 0.001). Moreover, it improved after TOT placement more in group A than in group B (P = 0.001).

Conclusions:

Ultralow-dose topical vaginal ovules containing 0.03 mg estriol administrated before and after TOT placement could improve the vaginal epithelium maturation of postmenopausal women affected by SUI. Moreover, vaginal estriol ovules also improved the surgical outcome investigated by SF-36 and FSFI.
The effect of metformin on vertebral marrow fat in postmenopausal women with newly diagnosed type 2 diabetes mellitus
Authors: Lin Fang , Pan Yuning , Zhang Yinwei , Zhou Qiang
Published: December 2019

Objective:

To determine the effect of metformin on marrow adiposity in postmenopausal women with newly diagnosed type 2 diabetes mellitus (T2DM).

Methods:

We enrolled 25 postmenopausal T2DM women who satisfied the requirement of having been on 1 year of metformin therapy and 26 age-matched healthy women receiving a placebo. All participants were analyzed for marrow fat fraction (FF) by magnetic resonance spectroscopy, vertebral volumetric bone mineral density (vBMD) by quantitative computed tomography, blood glucose, lipid profiles, and bone biomarkers to compare values before and after the interventions. Differences between groups were assessed using a Student's t test and chi-square test or an analysis of covariance adjusted for covariates. Twelve-month change in within-group difference was assessed using paired t tests. Correlations were determined by Pearson's correlation.

Results:

Vertebral vBMD was lower in T2DM than in nondiabetic controls (105.6 ± 13.8 vs 112.8 ± 15.2 mg/cm3; P = 0.029). T2DM women had a higher marrow FF than those without diabetes (66.3 ± 7.2% vs 58.9 ± 7.5%; P < 0.001), even after adjusting for covariates. From baseline to month 12 in the T2DM group, metformin was associated with a reduction in marrow FF (−12.0%; P < 0.001) and an increase in vBMD (3.7%; P = 0.020). For metformin-treated T2DM women, the 12-month change in marrow FF was inversely associated with change in vBMD (r = −0.771, P < 0.001), but not with changes in bone biomarkers, whereas change in vBMD or FF was not significant in the control group.

Conclusion:

Postmenopausal women with newly diagnosed T2DM have a higher marrow fat content compared with nondiabetic women. Metformin treatment reduced marrow adiposity in T2DM.
Online Family Problem-Solving Therapy (F-PST) for Executive and Behavioral Dysfunction After Traumatic Brain Injury in Adolescents: A Randomized, Multicenter, Comparative Effectiveness Clinical Trial
Authors: Kurowski Brad G. , Taylor H. Gerry , McNally Kelly A. , Kirkwood Michael W. , Cassedy Amy , Horn Paul S. , Stancin Terry , Wade Shari L.
Published: December 2019

Objective:

To examine the comparative effectiveness of 3 modes of family problem-solving therapy (F-PST): therapist-guided online, self-guided online, and face-to-face.

Setting:

Four children's hospitals and a general hospital with pediatric commitment.

Participants:

A total of 150 adolescents aged 14 to 18 years, previously hospitalized with traumatic brain injury (TBI), and evidence of behavior problems at enrollment.

Design:

Multicenter, randomized clinical trial.

Main Measures:

Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC), Behavior Regulation Index, and Metacognition Index, and Strengths and Difficulties Questionnaire (SDQ) Total at baseline and 6 and 9 months later.

Results:

Mixed-model intention-to-treat analyses of comparative effectiveness failed to reveal statistically significant differences among treatment groups. At 6 months, parent BRIEF-GEC improved for the therapist-guided and self-guided, online groups. Effects remained significant and increased in magnitude at 9 months for the self-guided online group. Scores for the Self-guided online group significantly improved from baseline to 9 months on the SDQ Total.

Conclusions:

This comparative effectiveness study supports the utility of both self- and therapist-guided online F-PST in improving executive function behaviors in adolescents following TBI. Further work regarding clinical implementation and how best to integrate telehealth with ongoing rehabilitation care is warranted.
Impact of Secondary ADHD on Long-Term Outcomes After Early Childhood Traumatic Brain Injury
Authors: Narad Megan E. , Riemersma Jacqlyn , Wade Shari L. , Smith-Paine Julia , Morrison Paige , Taylor H. Gerry , Yeates Keith Owen , Kurowski Brad G.
Published: December 2019

Objective:

To examine the impact of secondary attention-deficit/hyperactivity disorder (SADHD) on long-term global and executive functioning in adolescents after traumatic brain injury (TBI).

Setting:

Three tertiary cared children's hospitals and 1 general hospital.

Participants:

One hundred twenty children (TBI: n = 54; orthopedic injury: n = 66) without preinjury ADHD evaluated approximately 6.8 years postinjury.

Design:

Cross-sectional data analysis from a prospective, longitudinal study.

Main Measures:

Outcomes included functional impairment (Child and Adolescent Functional Assessment Scale) and executive functioning (Behavior Rating Inventory of Executive Function [BRIEF]).

Results:

SADHD moderated the association of injury type with the BRIEF-Behavioral Regulation Index (F
1,113 = 4.42, P = .04) and the Child and Adolescent Functional Assessment Scale (F
1,112 = 8.95, P = .003). TBI was only associated with poorer outcomes in the context of SADHD. SADHD was also associated with poorer outcomes on the BRIEF-Global Executive Composite (F
1,113 = 52.92, P < .0001) and BRIEF-Metacognitive Index scores (F
1,113 = 48.64, P < .0001) across groups. Adolescents with TBI had greater BRIEF-Global Executive Composite scores than those with orthopedic injury (F
1,113 = 5.00, P = .03).

Conclusions:

Although SADHD was associated with poorer functioning across groups, its adverse effects on behavioral regulation and overall functioning were amplified following TBI. TBI + SADHD may confer an elevated risk for significant impairments in early adolescence.
The Effect of Second-Generation Antidepressant Treatment on the Memory of Patients With Major Depressive Disorder
Authors: Gudayol-Ferré Esteve , Duarte-Rosas Patricia , Peró-Cebollero Maribel , Guàrdia-Olmos Joan
Published: December 2019

Background

Major depressive disorder (MDD) has been linked to episodic memory deficits that may be improved after pharmacological treatment, but it is unclear whether there is a class of antidepressants that is more effective than others to ameliorate these deficits in MDD. In addition, the possible effects of clinical and sociodemographic variables on the improvement of MDD memory deficits after pharmacological treatment are currently unknown. Our aims are to study the possible neuropsychological effects of second-generation antidepressant classes on the episodic memory of MDD patients and to study the potential effects of clinical and demographic variables as moderators of the effects of antidepressants on the memory of depressed patients through a meta-analysis approach.

Procedures

Nine articles were included in our study. A structural equation model meta-analysis was performed.

Results

Our results suggest that selective serotonin reuptake inhibitors and serotonine-noradrenaline reuptake inhibitors would bring about a substantial improvement in the memory of depressed patients, whereas other antidepressant classes would cause rather modest effects. Our results also suggest that clinical and demographic variables play a very important role as mediators of memory improvement after MDD treatment. Thus, a relatively low level of symptom severity, a high degree of clinical improvement, a younger age, and more years of education were positively related to memory improvement after MDD treatment.

Conclusions

Although antidepressant class is an important variable linked to memory improvement in MDD, overall, the degree of memory amelioration in depression is very closely related to clinical and demographic variables of patients with depression.
Biperiden Selectively Impairs Verbal Episodic Memory in a Dose- and Time-Dependent Manner in Healthy Subjects
Authors: Borghans Laura , Sambeth Anke , Blokland Arjan
Published: December 2019

Purpose/Background

Biperiden is a muscarinic antagonist that produces memory impairments without impairing attention or motor functions in healthy subjects. It has been suggested that a biperiden-induced memory deficit could model age- and dementia-related memory impairments. The goal of the current study was to determine the dose- and time-dependent effects of biperiden on cognition in healthy volunteers.

Methods/Procedures

Twenty-one healthy volunteers participated in a placebo-controlled, 3-way, crossover study. After a baseline test, cognitive performance was tested at 3 time points after a single dose of biperiden 2 or 4 mg, or placebo. Episodic memory was measured using a 15-word verbal learning task (VLT). Furthermore, n-back tasks, a sustained attention to response task and a reaction time task were used, as well as subjective alertness and a side effects questionnaire. In addition, blood serum values and physiological measures were taken.

Findings/Results

Biperiden decreased the number of words recalled in immediate and delayed recall of the VLT 90 minutes after drug intake. A dose-dependent impairment was found for the delayed recall, whereas the immediate recall was equally impaired by the 2 doses. Biperiden did not affect the performance on the VLT 4 hours after administration. Performance in the n-back task and the sustained attention to response task were not affected by biperiden at any time point. Both doses were well tolerated as reported side effects were mild at T
max and were minimal at the other time points.

Implications/Conclusions

Biperiden exerts effects on episodic memory without negatively affecting other cognitive performance and behavioral measures that were assessed in this study. The data provide further evidence that biperiden has selective effects on cognition, even after a high dose.
Lower Prolactin Levels in Patients Treated With Aripiprazole Regardless of Antipsychotic Monopharmacy or Polypharmacy
Authors: Sugai Takuro , Suzuki Yutaro , Yamazaki Manabu , Sugawara Norio , Yasui-Furukori Norio , Shimoda Kazutaka , Mori Takao , Ozeki Yuji , Matsuda Hiroshi , Okamoto Kurefu , Sagae Toyoaki , Someya Toshiyuki
Published: December 2019

Background

Hyperprolactinemia is a troublesome adverse effect of antipsychotics. Aripiprazole (ARP), which is one of second-generation antipsychotics, has been reported to lower serum prolactin (PRL) levels. However, few studies have compared the effect of ARP on plasma PRL levels between monopharmacy and polypharmacy with antipsychotics.

Methods

We conducted a large-scale investigation of the physical risk for inpatients with schizophrenia using a questionnaire covering demographic data, the number, dose and type of antipsychotics, and serum PRL levels.

Results

Sufficient data to conduct an assessment of the effect on PRL levels between antipsychotic monopharmacy and polypharmacy were obtained from 316 of the inpatients. Serum PRL levels in ARP combination group were lower than non-ARP combination group, regardless of antipsychotic monopharmacy or polypharmacy.

Conclusions

The present study suggests that ARP lowers serum PRL levels regardless of monopharamacy or polypharmacy with antipsychotics.
Clinical Risk Factors for Therapeutic Lithium-Associated Electrocardiographic Changes in Patients With Bipolar Disorder
Authors: Chen Pao-Huan , Kao Yu-Hsun , Chang Chi-Kang , Lin Yen-Kuang , Lin Yuan-Feng , Chen Yi-Jen
Published: December 2019

Purpose/Background

Lithium, a common medication used in bipolar disorder treatment, can exert an inhibitory effect on sodium and potassium channels and potentially cause cardiac electrical conduction disturbance and corrected QT (QTc) prolongation. This study aimed to examine whether lithium at therapeutic levels can change electrocardiographic parameters in different groups of patients with bipolar disorder and to identify the potential clinical risk factors.

Methods/Procedures

Standard 12-lead electrocardiogram data before and after lithium treatment in bipolar disorder patients after at least 2-week dropout of psychotropic medications were analyzed.

Findings/Results

A total of 39 patients with bipolar disorder receiving lithium treatment were enrolled. Nineteen patients (48.7%) exhibited increased from P wave beginning to QRS complex beginning intervals after lithium treatment (mean serum level, 0.653 ± 0.247 mmol/L). Twenty-four patients (61.5%) exhibited increased a combination of Q, R, and S waves complex durations and increased QTc intervals. Twenty-three patients (59.0%) exhibited increased corrected JT (JTc) intervals. The patient group with increased QTc or JTc intervals exhibited a higher mean systolic blood pressure than did the patient group without increased QTc (134.7 ± 19.2 mm Hg vs 115.7 ± 11.8 mm Hg, P = 0.020) or JTc intervals (134.4 ± 19.6 mm Hg vs 117.6 ± 13.3 mm Hg, P = 0.054), respectively. Biochemical and hemodynamic parameters were comparable between patients with and without increased a combination of Q, R, and S waves complex durations or from P wave beginning to QRS complex beginning intervals.

Implications/Conclusions

Elevated systolic blood pressure may be the risk factor for the ventricular conduction delay in bipolar disorder patients receiving lithium at therapeutic levels.
Sarcopenia is associated with longer hospital stay and multiorgan dysfunction in alcoholic hepatitis
Authors: Al-Azzawi Yasir , Albo Betty , Fasullo Matthew , Coukos Jennifer , Watts George J. , Tai Ryan , Radcliffe David , Kroll-Desrosiers Aimee , Devuni Deepika , Szabo Gyongyi
Published: December 2019

Introduction:

Excessive alcohol consumption has steadily risen to become the third leading cause of preventable death in the USA. One consequence of heavy alcohol use recently under considerable investigation is alcoholic hepatitis. Although many risk factors for developing alcoholic hepatitis have been documented, our aim in this study was to examine the potential association between sarcopenia and severity, mortality, 30 days readmission rate, complication, infections and length of hospital stay in alcoholic hepatitis patients.

Methods:

A retrospective analysis was performed at a large, academic hospital in 194 alcoholic hepatitis patients aged 18–60 who had cross-sectional computed tomography imaging and met our clinical definition of alcoholic hepatitis. The fifth percentile of the psoas muscle index was used as a cutoff for sarcopenia.

Results:

One hundred ninety-four patients met the criteria for alcoholic hepatitis and had cross-sectional imaging. Higher Model for End-Stage Liver disease score was found in the sarcopenia group when compared to the non-sarcopenia group (mean Model for End-Stage Liver disease 21.5 and 24.2, respectively, P = 0.03). Sarcopenia also correlated with significantly longer hospital stay; the average length of stay in the sarcopenia group was 17.2 days while the non-sarcopenia patients had an average of 12.4 days. We found higher risk of developing pneumonia, sepsis and hepatic encephalopathy in sarcopenic patients.

Conclusion:

Alcoholic hepatitis patients with sarcopenia have significantly worse outcomes when compared with the patients without sarcopenia, including a severe form of alcoholic hepatitis, longer hospital stays, higher risk of developing pneumonia, sepsis and hepatic encephalopathy.
Bioanalytical Assessment of Plasma Concentrations of Angiotensin-Converting Enzyme II Inhibitors and Angiotensin Receptor Blockers: A Pilot Study Among Patients Hospitalized With Acute Heart Failure
Authors: McNaughton Candace D. , Collins Sean P. , Lindenfeld JoAnn , Morrison Ryan , Daniels John Scott , Wang Thomas J.
Published: December 2019

Background:

Although angiotensin-converting enzyme II inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) improve chronic heart failure (HF) outcomes, their potential harms and benefits in acute HF (AHF) is less clear.

Study Question:

We explored the relationship between ACEI or ARB plasma concentrations among patients with AHF with in-hospital change in estimated glomerular filtration rate (eGFR).

Data Sources and Study Design:

From August 2016–June 2017, patients with AHF prescribed an outpatient ACEI or ARB were enrolled before AHF treatment. All patients were given twice their home dose of diuretic intravenously and received clinical care at the discretion of the medical team. Of 61 patients in the parent study, saved plasma from 34 who were prescribed an outpatient ACEI or ARB was included in this substudy.

Measures and Outcomes:

Liquid chromatography–tandem mass spectrometry was performed to assess ACEI or ARB plasma concentrations before AHF treatment. Change in eGFR was computed using the Chronic Kidney Disease Epidemiology Collaboration equation, which adjusts for age, sex, and race; diuretic dose and enrollment eGFR were used to adjust for HF severity. Multiple linear regression adjusting for enrollment eGFR and diuretic dose was performed to examine the relationship between drug concentration (undetectable/low vs. in/above-range) and in-hospital change in eGFR.

Results:

Of 34 patients with AHF, median age was 63 years (interquartile range, 58–78 years), 19 (55.9%) were women, median eGFR at enrollment was 55.6 mL/min (interquartile range, 35.2–75.3 mL/min), and for 11 (32.4%), no ACEI or ARB was detectable in plasma. Medication concentrations in- or above-reference range were associated with in-hospital decrease in eGFR of 8.3 mL/min (95% confidence interval, 15.3–1.3 mL/min decrease), after adjusting for enrollment eGFR and diuretic treatment.

Conclusions:

Bioanalytical assessment of medication levels may be useful to guide in-hospital ACEI and ARB therapy for patients with AHF.
Effects of Evidence-Based Continuing Care Bundle on Health Outcomes in Rectal Cancer Patients With Temporary Stomas
Authors: Su Xi , Zhong Mei-hua , Ye Xin-mei , Zhen Li , Yin Xue-xia , Qin Fang , Zhu Mu-lan , Kuang Yin-yi , Wang Hui-zhen
Published: December 2019

Background

The patients with temporary stomas after anterior resection for rectal cancer may experience significant impact on their health outcomes, and hence continuing care is necessary and important for these patients. However, the effects of some single continuing care interventions remain unclear. Continuing care bundle may be an effective approach to address this uncertainty.

Objective

The aim of this study was to investigate the effects of an evidence-based continuing care bundle on selected health outcomes in patients with temporary stomas after anterior resection for rectal cancer.

Methods

This was a multicenter randomized controlled trial. A total of 124 patients with temporary stomas after anterior resection for rectal cancer were recruited from 4 general tertiary hospitals in Guangzhou, China, and were randomly assigned to a control group or an intervention group. Both groups received usual care, whereas the intervention group additionally received evidence-based continuing care bundle. Self-efficacy, quality of life, and stoma-related complications were collected at baseline and 4 and 12 weeks after surgery. Satisfaction and outcomes of stoma reversal were collected at the end of the observation.

Results

The intervention group had significantly improved the self-efficacy (F = 11.88, P = .001), quality of life (F = 17.99, P < .001) over time, satisfaction (t = 4.08, P < .001), and outcomes of stoma reversal (χ
2 = 5.93, P = .015) and reduced the incidence of complications (P < .05).

Conclusions

Evidence-based continuing care bundle can be an effective method to improve the health outcomes among these patients

Implication for Practice

By using the evidence-based continuing care bundle, nurses can help these patients improve their health outcomes in stoma-specific nursing.
Losing Her: Children's Reported Concerns in the First 6 Months of Their Mother's Breast Cancer Diagnosis
Authors: Almulla Hebah Ahmed , Lewis Frances Marcus
Published: December 2019

Background

Maternal breast cancer has a significant impact on the well-being of school-aged children, but we know very little about the concerns these children attribute to their mother's illness.

Objective

The aim of this study was to describe child-reported illness-related concerns experienced in the initial 6 months of their mother's diagnosis and to identify any differences by age and gender of the child.

Methods

Data were obtained from 140 school-aged children (7–12 years) within 6 months of their mother diagnosis with stage 0 to III breast cancer. Children's written responses to an open-ended question were analyzed: “Think about a situation that has bothered you during the last month that had to do with your mom's breast cancer.” Inductive content analysis was used to analyze the data using methods adapted from grounded theory. Trustworthiness of results was protected by coding to consensus, formal peer debriefing, and maintaining an audit trail.

Results

“Losing Her”, the core construct, was identified and organized the children's concerns in 4 domains: (1) her being away from me, (2) worrying about her, (3) seeing my mother be different, and (4) changing how things work.

Conclusion

All children reported illness-related concerns about which they were bothered. Even seemingly short-term treatment-related absences from the child were interpreted as difficult.

Implication for Practice

Findings from the current study add to nurses' awareness and knowledge about the concerns of school-aged children during their mother's initial treatment of breast cancer. Nurses are in a key position to provide services directly to the child or through the mother.
Managing Patients With Severe and Enduring Anorexia Nervosa
Authors: Yager Joel
Published: December 2019

Objective

Approximately 20% of patients with anorexia nervosa develop severe and enduring anorexia nervosa (SE-AN), manifest by decades-long illnesses. At certain points, demoralized and/or based on judicious appraisals of the seeming futility of further professional treatment to radically alter their course, some SE-AN patients decide that “enough is enough” and opt out of intensive treatment. This article considers courses and treatment options available at these stages for patients, families, and clinicians.

Methods

The author uses clinical illustrations, Socratic questioning, and available literature to explore questions of treatment strategies with patients struggling with SE-AN.

Results

SE-AN patients have frequently received care in varieties of medical, psychiatric, and specialized eating disorders inpatient, residential, partial hospital, and outpatient treatment settings. Patients may reject further high-intensity treatment for judicious or capricious reasons, but may still accept lower intensity treatments. Some may reject any and all offers of treatment. Clinicians' treatment recommendations, not always coinciding with patients' wishes, are influenced by numbers of clinical, social, and professional pressures, including those from families, treatment settings, regulatory bodies, and payors.

Conclusions

When managing patients with decades-long disease and multiple comorbidities, clinicians must be realistic about the low odds of effecting cure and adjust treatment expectations accordingly. For patients with SE-AN, a variety of low-intensity treatment approaches, at times extending to palliative and hospice care, may be useful. Clinicians should always strive to provide humane comfort and support, as closely aligned to patients' judicious wishes as realistically possible.
Hepatitis C virus or hepatitis B virus coinfection and lymphoma risk in people living with HIV
Authors: Besson Caroline , Noel Nicolas , Lancar Remi , Prevot Sophie , Algarte-Genin Michele , Rosenthal Eric , Bonnet Fabrice , Meyohas Marie-Caroline , Partisani Marialuisa , Oberic Lucie , Gabarre Jean , Goujard Cécile , Cheret Antoine , Arvieux Cedric , Katlama Christine , Salmon Dominique , Boué François , Costello Regis , Hendel-Chavez Houria , Taoufik Yassine , Fontaine Hélène , Coppo Paul , Mounier Nicolas , Delobel Pierre , Costagliola Dominique
Published: December 2019

Objective:

Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are associated with increased risks of lymphomas in the non-HIV setting. Their impacts on HIV-associated lymphomas deserved further studies in the modern combined antiretroviral therapy (cART) era.

Design:

We evaluated the associations between HCV, HBV and HIV-related lymphomas in the Lymphovir-ANRS-CO16 cohort.

Methods:

Prevalence of HCV seropositivity and chronic HBV infections were compared with those observed in the French Hospital Database on HIV (FHDH-ANRS-CO4).

Results:

Between 2008 and 2015, 179 patients with HIV-related lymphomas from 32 French hospitals were enrolled, 69 had Hodgkin's lymphoma (39%), and 110 non-Hodgkin's lymphoma (NHL) (61%). The prevalence of HCV infection was higher in patients with NHL than in the FHDH-ANRS-CO4 [26 versus 14%, odd ratio (OR): 2.15; 95% confidence interval (1.35–3.32)] whereas there was no association between Hodgkin's lymphoma and chronic HCV infection. Chronic HBV infection was not associated with NHL in our cohort with a prevalence of 5 versus 7% in FHDH-ANRS-CO4 but tended to be associated with Hodgkin's lymphoma [prevalence of 14%, OR: 2.16 (0.98–4.27)]. Chronic HCV infection tended to pejoratively impact 2-year overall survival in patients with NHL: 72% [57%, 91%] versus 82% [74%, 91%], hazard ratio: 2.14 [0.95–4.84]. In contrast, chronic HBV infection did not correlate with outcome.

Conclusion:

In the modern cART era, chronic HCV infection is associated with an increased risk of NHL in PLWHIV and tends to pejoratively impact overall survival. HBV infection is not associated with the risk of NHL but with a borderline increase of Hodgkin's lymphoma risk.
Antiviral (Hepatitis C Virus) Drug-Drug Interaction Leading to Dramatic Underestimation of Liver Function With 99mTc-Mebrofenin Hepatobiliary Scintigraphy
Authors: Deshayes Emmanuel , Fersing Cyril , Meunier Lucy , Quenet François , Guiu Boris
Published: December 2019

There is a growing interest in assessment of future remnant liver function with 99mTc-mebrofenin hepatobiliary scintigraphy before major hepatectomy to estimate the risk of posthepatectomy liver failure. We illustrate the case of a 42-year-old woman with liver metastasis from colorectal cancer who performed hepatobiliary scintigraphy. 99mTc-mebrofenin clearance rate of the total liver was considerably low. The patient recently started a treatment for active hepatitis C with a combination of 2 new direct-acting antiviral agents (grazoprevir, elbasvir). Apart from hypoalbuminemia or hyperbilirubinemia, physicians must be aware that drug interactions can interfere with 99mTc-mebrofenin liver uptake, thereby resulting in a dramatic underestimation of liver function.
Abdominal Wall Granulomatous Inflammation Mimicking Malignancy on FDG PET/CT
Authors: Shen Guohua , Kuang Anren
Published: December 2019

An old woman with abdominal pain complained a palpable mass on the right anterior abdominal wall. On PET/CT images, the lesion presented as a soft tissue mass with irregular shape, invading adjacent peritoneum and showing intense FDG uptake. Based on imaging findings, a malignancy was suspected, and she underwent surgical resection. However, the abdominal wall mass was diagnosed as granulomatous inflammation with a little necrosis by pathological results. Awareness of this benign disease is helpful for an accurate diagnosis of abdominal wall mass.
Asymmetric 67Ga Activity in the Head Related to Prior Head Trauma
Authors: Bai Xia , Wang Xuemei
Published: December 2019

67Ga study was performed in a 10-year-old boy who had a history of motor vehicle accident to evaluate occult infection. No abnormal activity typical of active infection was noted. However, there was significantly decreased activity in the right side of the head, which was related to his head trauma.
SPECT/CT Demonstrating 131I Accumulation in Gallbladder Stone in a Thyroid Cancer Patient
Authors: Shao Fuqiang , Long Yu , Chen Xiaomin , Lan Xiaoli
Published: December 2019

The radioiodine in the gallbladder usually mimics focal hepatic activity on the planar 131I whole-body scintigraphy. Here we describe an abnormal uptake in the hepatic region on postablative 131I scintigraphy in a 37-year-old woman with papillary thyroid cancer. The SPECT/CT images revealed this “hepatic activity” corresponded to gallbladder stone.
A Rare Case of Primary Ventricular Lymphoma Presented on FDG PET/CT
Authors: Wang Dong , Su Min , Xiao JingXing
Published: December 2019

Primary ventricular lymphoma is a rare form of non-Hodgkin lymphoma confined to the central nervous system. A 51-year-old woman presented with a 4-month history of unsteady gait and progressive decline in memory. An outside brain MRI showed multiple space-occupying lesions in the ventricles, which suggested malignancy. Staging with FDG PET/CT demonstrated not only hypermetabolic masses in the lateral, third, and fourth ventricles but also a hypermetabolic lesion in the spinal cord. A biopsy of the right lateral ventricle tumor confirmed diffuse large B-cell lymphoma.
Primary Merkel Cell Carcinoma
Authors: Liao Wen-Chieh , Keng Chen , Ma Hsu , Hsu Chih-Yi
Published: December 2019

Background

Merkel cell carcinoma (MCC) is rare among Asians. To evaluate the presence and characteristics of MCC in Taiwan, we described the characteristics, treatment, and prognostic findings of MCC in our institution.

Methods

We revisited and carried out a retrospective chart review of 16 consecutive patients with MCC treated from 1995 to 2018. Patient demographic data, tumor size, location, previous treatment, and follow-up data about presence of locoregional recurrence and metastasis were evaluated.

Results

There were 14 male and 2 female patients (mean age = 75.1 years; range = 26–91 years). Clinical follow-up revealed local recurrences in 5 patients 1 to 4 months after surgical excision. Lymph node metastasis was observed in 3 patients. We reviewed previously published articles and analyzed the clinical findings, pathologic examinations, and treatments.

Conclusions

Surgical wide excision of the primary tumor remains the mainstay of treatment for patients with local/regional MCC. Additional management strategies, such as lymphadenectomy, radiotherapy, chemotherapy, and targeted therapy, depend on the presence or absence of clinically detectable lymph node disease. The prognosis for MCC is variable. Our findings highlight the importance of maintaining a high clinical suspicion for this malignancy in the appropriate clinical context to avoid delays in diagnosis and management.
Incidence and Risk of Carpal Tunnel Syndrome in End-Stage Renal Disease Patients on Dialysis
Authors: Tsai Chia-Hsuan , Hsu Hsiang-Hao , Chen Shih-Heng , Chien Ling , Lin Jennifer An-Jou , Chang Chee-Jen , Kao Huang-Kai
Published: December 2019

Carpal tunnel syndrome (CTS) is a common cause of compression neuropathy of the upper extremities. This retrospective nationwide matched cohort study was conducted using the data from the Taiwan National Health Insurance Research Database between January 2003 and December 2012. The incidence rate of CTS was 975.84 and 544.12/100,000 person-years, respectively, yielding an incidence rate ratio of 1.79 (95% confidence interval, 1.68-1.91, P < 0.0001). CTS patients with End-stage renal disease (ESRD) in the dialysis group were more likely to receive surgical intervention than those the control group (62.41% vs 12.89%, P < 0.0001). The risk of CTS was significantly higher in the ESRD on dialysis cohort (10-year cumulative incidence, 8.0%) than in the control cohort (5.1%), which yielded an adjusted hazard ratio of 13.95 (95% confidence interval, 10.95–17.76, P < 0.0001). The high risk of CTS in ESRD patients on dialysis suggests that timely referral to hand surgeons with appropriate treatment should prevent permanent median nerve damage by CTS and may possibly improve patients' quality of life.
Gait Improvement and Ulcer Prevention With Second-to-Great Toe Transposition at the Donor Site
Authors: Yang Cristhiam , Hsieh Yu-Hsuan , Chen Hsin-Hung , Tsai Chia-Hsuan , Lin Yu-Te
Published: December 2019

A young male patient, who sustained a severe burn injury 6 years ago, received amputation of left hand at the level of metacarpal shaft of the thumb and base of proximal phalanxes of the rest of the fingers. Staged operations, including combined second- and third-toe transfer from the right foot to middle and ring fingers of the left hand, and harvest of great toe from the left foot for reconstruction of left thumb, were successively executed. Unfortunately, callus and ulcer were found at the plantar area of first metatarsophalangeal joint of left donor foot in the following 2 years, which caused troublesome disturbance during ambulation. We hereby present how second toe transposition can decrease the donor foot pain and prevent the recurrence of plantar ulcer after 21 months of follow-up.
Otolith chemistry indicates recent worsened Baltic cod condition is linked to hypoxia exposure
Authors: Limburg Karin E. , Casini Michele
Published: December 2019

Deoxygenation worldwide is increasing in aquatic systems with implications for organisms' biology, communities and ecosystems. Eastern Baltic cod has experienced a strong decline in mean body condition (i.e. weight at a specific length) over the past 20 years with effects on the fishery relying on this resource. The decrease in cod condition has been tentatively linked in the literature to increased hypoxic areas potentially affecting habitat range, but also to benthic prey and/or cod physiology directly. To date, no studies have been performed to test these mechanisms. Using otolith trace element microchemistry and hypoxia-responding metrics based on manganese (Mn) and magnesium (Mg), we investigated the relationship between fish body condition at capture and exposure to hypoxia. Cod individuals collected after 2000 with low body condition had a higher level of Mn/Mg in the last year of life, indicating higher exposure to hypoxic waters than cod with high body condition. Moreover, lifetime exposure to hypoxia was even more strongly correlated to body condition, suggesting that condition may reflect long-term hypoxia status. These results were irrespective of fish age or sex. This implies that as Baltic cod visit poor-oxygen waters, perhaps searching for benthic food, they compromise their own performance. This study specifically sheds light on the mechanisms leading to the low condition of cod and generally points to the impact of deoxygenation on ecosystems and fisheries.
Ocean acidification changes the vertical movement of stone crab larvae
Authors: Gravinese Philip M. , Enochs Ian C. , Manzello Derek P. , van Woesik Robert
Published: December 2019

Anthropogenic activities are increasing ocean temperature and decreasing ocean pH. Some coastal habitats are experiencing increases in organic runoff, which when coupled with a loss of vegetated coastline can accelerate reductions in seawater pH. Marine larvae that hatch in coastal habitats may not have the ability to respond to elevated temperature and changes in seawater pH. This study examined the response of Florida stone crab (
Menippe mercenaria
) larvae to elevated temperature (30°C control and 32°C treatment) and CO
2
-induced reductions in pH (8.05 pH control and 7.80 pH treatment). We determined whether those singular and simultaneous stressors affect larval vertical movement at two developmental stages. Geotactic responses varied between larval stages. The direction and rate of the vertical displacement of larvae were dependent on pH rather than temperature. Stage III larvae swam upwards under ambient pH conditions, but swam downwards at a faster rate under reduced pH. There was no observable change in the directional movement of Stage V larvae. The reversal in orientation by Stage III larvae may limit larval transport in habitats that experience reduced pH and could pose challenges for the northward dispersal of stone crabs as coastal temperatures warm.
Does urbanization favour exotic bee species? Implications for the conservation of native bees in cities
Authors: Fitch Gordon , Wilson Caleb J. , Glaum Paul , Vaidya Chatura , Simao Maria-Carolina , Jamieson Mary A.
Published: December 2019

A growing body of research indicates that cities can support diverse bee communities. However, urbanization may disproportionately benefit exotic bees, potentially to the detriment of native species. We examined the influence of urbanization on exotic and native bees using two datasets from Michigan, USA. We found that urbanization positively influenced exotic—but not native—bee abundance and richness, and that this association could not be explained by proximity to international ports of entry, prevalence of exotic flora or urban warming. We found a negative relationship between native and exotic bee abundance at sites with high total bee abundance, suggesting that exotic bees may negatively affect native bee populations. These effects were not driven by the numerically dominant exotic honeybee, but rather by other exotic bees. Our findings complicate the emerging paradigm of cities as key sites for pollinator conservation.
Transcription closed and open complex formation coordinate expression of genes with a shared promoter region
Authors: Häkkinen Antti , Oliveira Samuel M. D. , Neeli-Venkata Ramakanth , Ribeiro Andre S.
Published: December 2019

Many genes are spaced closely, allowing coordination without explicit control through shared regulatory elements and molecular interactions. We study the dynamics of a stochastic model of a gene-pair in a head-to-head configuration, sharing promoter elements, which accounts for the rate-limiting steps in transcription initiation. We find that only in specific regions of the parameter space of the rate-limiting steps is orderly coexpression exhibited, suggesting that successful cooperation between closely spaced genes requires the coevolution of compatible rate-limiting step configuration. The model predictions are validated using
in vivo
single-cell, single-RNA measurements of the dynamics of pairs of genes sharing promoter elements. Our results suggest that, in
E. coli
, the kinetics of the rate-limiting steps in active transcription can play a central role in shaping the dynamics of gene-pairs sharing promoter elements.
Radiation protraction schedules for low-grade gliomas: a comparison between different mathematical models
Authors: Budia I. , Alvarez-Arenas A. , Woolley T. E. , Calvo G. F. , Belmonte-Beitia J.
Published: December 2019

We optimize radiotherapy (RT) administration strategies for treating low-grade gliomas. Specifically, we consider different tumour growth laws, both with and without spatial effects. In each scenario, we find the optimal treatment in the sense of maximizing the overall survival time of a virtual low-grade glioma patient, whose tumour progresses according to the examined growth laws. We discover that an extreme protraction therapeutic strategy, which amounts to substantially extending the time interval between RT sessions, may lead to better tumour control. The clinical implications of our results are also presented.
The use of extruded finite-element models as a novel alternative to tomography-based models: a case study using early mammal jaws
Authors: Morales-García Nuria Melisa , Burgess Thomas D. , Hill Jennifer J. , Gill Pamela G. , Rayfield Emily J.
Published: December 2019

Finite-element (FE) analysis has been used in palaeobiology to assess the mechanical performance of the jaw. It uses two types of models: tomography-based three-dimensional (3D) models (very accurate, not always accessible) and two-dimensional (2D) models (quick and easy to build, good for broad-scale studies, cannot obtain absolute stress and strain values). Here, we introduce extruded FE models, which provide fairly accurate mechanical performance results, while remaining low-cost, quick and easy to build. These are simplified 3D models built from lateral outlines of a relatively flat jaw and extruded to its average width. There are two types: extruded (flat mediolaterally) and enhanced extruded (accounts for width differences in the ascending ramus). Here, we compare mechanical performance values resulting from four types of FE models (i.e. tomography-based 3D, extruded, enhanced extruded and 2D) in
Morganucodon
and
Kuehneotherium
. In terms of absolute values, both types of extruded model perform well in comparison to the tomography-based 3D models, but enhanced extruded models perform better. In terms of overall patterns, all models produce similar results. Extruded FE models constitute a viable alternative to the use of tomography-based 3D models, particularly in relatively flat bones.
Assessing African grey parrots' prosocial tendencies in a token choice paradigm
Authors: Krasheninnikova Anastasia , Brucks Désirée , Blanc Sigrid , von Bayern Auguste M. P.
Published: December 2019

Prosociality is defined as a voluntary, typically low-cost behaviour that benefits another individual. Social tolerance has been proposed as a potential driver for its evolution, both on the proximate and on the ultimate level. Parrots are an interesting species to study such other-regarding behaviours, given that they are highly social and stand out in terms of relative brain size and cognitive capacity. We tested eight African grey parrots in a dyadic prosocial choice test. They faced a choice between two different tokens, a prosocial (actor and partner rewarded) and a selfish (only actor rewarded) one. We found that the birds did not behave prosocially when one subject remained in the actor role; however, when roles were alternated, the birds’ prosocial choices increased. The birds also seemed to reciprocate their partner's choices, given that a contingency between choices was observed. If the food provisioned to the partner was of higher quality than that the actor obtained, actors increased their willingness to provide food to their partner. Nonetheless, the control conditions suggest that the parrots did not fully understand the task's contingencies. In sum, African grey parrots show the potential for prosociality and reciprocity; however, considering their lack of understanding of the contingencies of the particular tasks used in this study, the underlying motivation for the observed behaviour remains to be addressed by future studies, in order to elucidate the phylogenetic distribution of prosociality further.