bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological characteristics of primary lung nuclear protein in testis carcinoma: A single‐institute experience of 10 cases
Authors: Cho Yoon Ah , Choi Yoon‐La , Hwang Inwoo , Lee Kyungjong , Cho Jong Ho , Han Joungho
Published: October 2020

Background

Nuclear protein in testis (NUT) carcinoma is a rare tumor associated with NUT rearrangement that can present as poorly differentiated to undifferentiated carcinoma, with or without abrupt squamous differentiation. It is often misdiagnosed as poorly differentiated carcinoma or undifferentiated carcinoma if NUT is not suspected. In this study, we retrospectively analyzed pulmonary NUT carcinoma cases diagnosed with NUT immunohistochemical staining and discuss the differential diagnosis to provide information for this rare and aggressive entity.

Methods

Cases, diagnosed as “NUT carcinoma” in lung pleura and “metastatic NUT carcinoma from the lung” in lymph nodes were diagnosed between 2017 and 2019 at the Samsung Medical Center (SMC). Clinical features such as age, sex, treatment and follow‐up period, and pathological reports were obtained by reviewing patients’ electronic medical records.

Results

A total of 10 NUT carcinoma cases were found in the SMC pathology database. Seven patients were men and six were non‐smokers. Tumor cells showed various cellular features such as round, squamoid, and spindle. Some cases had initially been misdiagnosed as spindle cell neoplasm, round cell sarcoma, squamous cell carcinoma and small cell carcinoma. All cases showed diffuse strong nuclear expression of NUT immunohistochemical staining, and some were positive for p63 staining and negative for CD56 staining.

Conclusions

NUT carcinoma is often misdiagnosed because of its various morphologies. It is important to consider NUT as one of the differential diagnoses when encountering lung biopsy with undifferentiated morphology.

Key points

Due to various morphological features, NUT carcinoma can be misdiagnosed

It is important to consider NUT carcinoma when diagnosing a poorly differentiated or undifferentiated tumor
Nursing Diagnosis of Grieving in Cases of Perinatal Loss: A Preliminary Clinical Validation
Authors: Paloma‐Castro Olga , Pastor‐Montero Sonia María , Carnicer Fuentes Concepción , Jesús Albar‐Marín María , Bas‐Sarmiento Pilar , Moreno‐Corral Luis Javier , Romero‐Sánchez José Manuel
Published: October 2020

PURPOSE

To develop a preliminary clinical validation the NANDA‐I nursing diagnosis “Grieving” in cases of perinatal loss.

METHODS

Descriptive cross‐sectional study using the Fehring model.

FINDINGS

The overall clinical validity index for the diagnosis was 0.15. Only four defining characteristics and five manifestations identified in the literature were validated.

CONCLUSIONS

The variability of manifestations identified in the study participants is considered to be detrimental to the overall clinical validity index.

IMPLICATIONS FOR NURSING PRACTICE

The clinical validity of the diagnosis could not be substantiated by the preliminary results of this study and, therefore, additional research is necessary to determine the ability of the diagnosis to adapt to perinatal loss situations in real contexts. Some manifestations have been proposed to NANDA‐I for inclusion as defining characteristics in the nursing diagnosis of grieving.

OBJETIVO

Validar clínicamente de forma preliminar el diagnóstico enfermero NANDA‐I duelo en caso de pérdida perinatal.

MÉTODOS

Estudio descriptivo transversal usando el modelo de Fehring.

RESULTADOS

El índice de validez clínica global del diagnóstico fue de 0.15. Se validaron únicamente cuatro características definitorias y cinco manifestaciones identificadas en la literatura.

CONCLUSIONES

Se considera que la variabilidad de las manifestaciones presentadas por los participantes actuó en detrimento del índice de validación clínica global.

IMPLICACIONES PARA LA PRÁCTICA ENFERMERA

La validez clínica del diagnóstico no pudo ser corroborada por los resultados preliminares de este estudio y, por tanto, se necesita investigación adicional para terminar la capacidad de este diagnóstico para adaptarse a las situaciones de pérdidas perinatales en contexto reales. Se han propuesto a NANDA‐I algunas manifestaciones para que sean incluidas como Características Definitorias del diagnóstico enfermero Duelo.
Age‐related impairment of declarative memory: linking memorization of temporal associations to GluN2B redistribution in dorsal CA1
Authors: Al Abed Alice Shaam , Sellami Azza , Potier Mylene , Ducourneau Eva‐Gunnel , Gerbeaud‐Lassau Pauline , Brayda‐Bruno Laurent , Lamothe Valerie , Sans Nathalie , Desmedt Aline , Vanhoutte Peter , Bennetau‐Pelissero Catherine , Trifilieff Pierre , Marighetto Aline
Published: October 2020

GluN2B subunits of NMDA receptors have been proposed as a target for treating age‐related memory decline. They are indeed considered as crucial for hippocampal synaptic plasticity and hippocampus‐dependent memory formation, which are both altered in aging. Because a synaptic enrichment in GluN2B is associated with hippocampal LTP in vitro, a similar mechanism is expected to occur during memory formation. We show instead that a reduction of GluN2B synaptic localization induced by a single‐session learning in dorsal CA1 apical dendrites is predictive of efficient memorization of a temporal association. Furthermore, synaptic accumulation of GluN2B, rather than insufficient synaptic localization of these subunits, is causally involved in the age‐related impairment of memory. These challenging data identify extra‐synaptic redistribution of GluN2B‐containing NMDAR induced by learning as a molecular signature of memory formation and indicate that modulating GluN2B synaptic localization might represent a useful therapeutic strategy in cognitive aging.
Reconsidering alcohol treatment non‐responders: psychosocial functioning among heavy drinkers 3 years following treatment
Authors: Pearson Matthew R. , Wilson Adam D. , Richards Dylan K. , Witkiewitz Katie
Published: October 2020

Background and aims

Psychosocial functioning among individuals who exceed low‐risk drinking limits (exceed three to four standard drinks for women/men) is heterogeneous. Among those who receive treatment for alcohol use disorder (AUD), recent research found that more than one‐half of those who exceeded low‐risk limits (i.e. treatment non‐responders) reported good psychosocial functioning, commensurate with those who were abstinent or low‐risk drinkers (i.e. treatment responders) up to 1 year following treatment. This study aimed to determine if good levels of psychosocial functioning are maintained beyond 1 year.

Design

Secondary analysis of 3‐year follow‐up data from Project MATCH (Matching Alcoholism Treatment to Client Heterogeneity) and the Combined Pharmacotherapies and Behavioral Interventions study (COMBINE), multi‐site alcohol clinical trials conducted in the United States.

Setting

Eleven sites in COMBINE and nine sites in Project MATCH.

Participants

Individuals with AUD from COMBINE and Project MATCH (n = 1383 and n = 1726) characterized in terms of drinking/functioning at 1‐year follow‐up and retained at 3‐year (n = 641 and n = 790) post‐treatment follow‐ups.

Measurements

Alcohol consumption measured by Form‐90 and psychosocial functioning assessed by various instruments at 3 years post‐treatment

Findings

High‐functioning non‐responders at 1 year post‐treatment maintained a high level of functioning 2 years later and were not significantly different from the abstainers/low‐risk drinkers on any functional outcomes (e.g. SF12 Mental Health Mean difference: –1.38 [95% confidence interval (CI) = −4.34, 1.57), SF12 Physical Health Mean difference: –0.43 (95% CI = −2.28, 3.13)].

Conclusions

Approximately one‐half of those who engage in some heavy drinking in the year following treatment for alcohol use disorder appear to maintain high levels of psychosocial functioning up to 3 years following treatment.
The relationships between the myocardial bridge and ramus interventricularis paraconalis characteristics in lamb and sheep
Authors: Gulmez Nurhayat , Sah Huseyin
Published: October 2020

The myocardial bridge (MB) is an anomaly that the myocardial fibres cover on a segment of the subepicardial coronary arteries or their branches in domestic animals and humans. The aim of the present study was to determine the relationships between the characteristics of the MB and ramus interventricularis paraconalis at three levels in lambs and adult sheep. Thirty‐three hearts (16 lambs and 17 sheep) were used to determine the MB (length, angle and thickness) and vessel (vessel diameter and thicknesses of tunica intima et media of ramus interventricularis paraconalis) characteristics. Independent‐samples t test was applied to compare variables between lambs and sheep. Spearman's correlation analysis was conducted to evaluate the relationships between bridge and vessel characteristics at three bridge levels. Length, angle and thickness of myocardial bridges were not significantly different between the lambs and sheep (p > .05). The mean length, angle and thickness were 24.9 ± 16.1 mm, 113.7 ± 11.2° and 1,098 ± 555 µm in 33 hearts, respectively. In lambs, the mean vessel diameters were 1,930 ± 742 µm (1,534–2,325 µm), 1,247 ± 665 µm (893–1,601 µm) and 865 ± 172 µm (774–957 µm) at the pre‐bridge, bridge and post‐bridge levels, respectively. In sheep, the mean vessel diameters in the same order were 1,861 ± 1,068 µm, 1,337 ± 308 µm and 1,287 ± 549 µm. The bridge prevalence was 100% in the samples examined. In conclusion, coronary arterial diseases related to myocardial bridge should not be expected in sheep for veterinary cardiology practice. It may also be concluded that the cross‐breeds of the Awassi and Chios sheep may be useful in experimental studies related to myocardial bridge surgery.
Surviving at the extreme: Chimpanzee ranging is not restricted in a deforested human‐dominated landscape in Uganda
Authors: McLennan Matthew R. , Hintz Benjamin , Kiiza Vicent , Rohen Jacqueline , Lorenti Georgia A. , Hockings Kimberley J.
Published: October 2020

Endangered wildlife increasingly inhabits human‐dominated landscapes outside protected areas. Large‐bodied mammals require large spaces, and their ranging may be especially impacted by landscape modifications including farming, road development and urbanisation. We studied the Wagaisa community of chimpanzees (Pan troglodytes) in Uganda, which inhabit a landscape characterised by high human population density, widespread deforestation, and rapid agricultural and infrastructural development. We aimed to assess whether this dynamic, fragmented environment constrains the chimpanzees’ ranging, and to identify critical habitat patches to aid their conservation. During March–May 2018, we assessed range use from locations of direct observations and indirect signs, corroborated by longer‐term behavioural monitoring of the chimpanzees (June 2018–December 2019). No evidence of limited ranging was found. The Wagaisa chimpanzees used an area measuring ≥ 43 km2 (100% MCP) and ranged extensively in the anthropogenic matrix. Most frequently used parts of the range (‘core habitat areas’) centred around small (5–20 acres), widely dispersed remnant forest patches and exotic eucalyptus plantations. Forty per cent of chimpanzee nests were constructed in eucalyptus trees, suggesting a behavioural adjustment to landscape changes. Actions to facilitate conservation of these ‘village chimpanzees’ and others surviving in transformed human‐dominated habitat need not conflict with the sustainable development of the region.
EyeSi Surgical Simulator: validation of a proficiency‐based test for assessment of vitreoretinal surgical skills
Authors: Jaud Charlotte , Salleron Julia , Cisse Cécile , Angioi‐Duprez Karine , Berrod Jean‐Paul , Conart Jean‐Baptiste
Published: October 2020

Purpose

To develop and investigate an evidence‐based performance test for assessment of vitreoretinal surgical skills on the EyeSi Surgical Simulator.

Methods

Ten junior residents without any surgical experience, eight senior residents with prior experience in cataract surgery and five vitreoretinal surgeons were included in the study. The test consisted of seven modules and was completed twice by all groups during a single session. Validity evidence was evaluated using Messick’s validity framework. Senior residents completed four additional test sessions and were retested 3 months after to assess skill acquisition and retention.

Results

Content was aligned with vitreoretinal surgical skills as evaluated by expert surgeons. Response process was ensured through standardized instruction and data collection. The test showed satisfactory internal consistency with Cronbach’s α = 0.76 (internal structure) and significant discriminative ability between the residents and the experienced surgeons (relation to other variables). A pass/fail level was determined at 596 using the contrasting groups’ method. Consequences of applying this standard resulted in no false positive and no false negative.

Senior residents significantly improved their simulator skills over time, reaching a plateau at the fifth iteration and equalling expert performance (p = 0.420). This level of competency was retained during the post‐3‐month retention testing (p = 0.062).

Conclusion

We established a performance test with solid evidence for assessment of vitreoretinal surgical skills on the EyeSi Simulator and determined a benchmark criterion that may be used for future implementation of proficiency‐based training for novices.
Pharmacological data of a successful 4‐days‐a‐week regimen in HIV antiretroviral therapy (ANRS 162‐4D trial)
Authors: Abe Emuri , Assoumou Lambert , de Truchis Pierre , Amat Karine , Gibowski Séverine , Gras Guillaume , Bellet Jonathan , Saillard Juliette , Katlama Christine , Costagliola Dominique , Girard Pierre‐Marie , Landman Roland , Alvarez Jean‐Claude
Published: October 2020

Introduction

Few data are available on plasma concentrations of antiretroviral therapy (ARV) during intermittent treatment.

Objective

To compare plasma concentrations in OFF vs ON treatment periods at several time points during treatment.

Methods

During a successful 48‐week multicenter study (ANRS 162‐4D trial) of 4 days with treatment (ON) followed by 3 days without treatment (OFF) in adults treated by two nucleoside analogues and a third agent belonging to a boosted protease‐inhibitor (PI, darunavir [DRV], atazanavir [ATV], lopinavir [LPV]) or a non‐nucleoside‐reverse‐transcriptase inhibitor (NNRTI, efavirenz [EFV], etravirine [ETR], rilpivirine [RPV]) conducted in 100 patients (96% success), we determined the plasma concentrations of ARV. Blood samples were collected for analysis at inclusion (W0, 7/7 strategy for all patients), W16 and W40 (ON) and at W4, W8, W12, W24, W32 and W48 (OFF).

Results

A total of 866 samples was analysed. Plasma concentrations were not statistically lower after 4 days (ON) vs 7/7 days of treatment except for RPV (−30 ng/mL at 4/7, P = 0.003). Significant lower plasma concentrations were observed for OFF vs ON except for ETR (n = 5, P = 0.062). Overall, 87.1% of ON concentrations (ATV 92.1%, DRV 51.1%, LPV 62.5%, EFV 94.4%, ETR 100% and RPV 94.9%) and 21.8% of OFF concentrations (ATV 1.4%, DRV 0.0%, LPV 0.0%, EFV 16.0%, ETR 92.6% and RPV 39.0%) were above the theoretical limit of efficacy of the molecule. In the OFF period, 85.8% of PI concentrations were under the limit of quantification, while 98.0% of NNRTI concentrations were quantifiable.

Conclusion

Despite low/undetectable PI/NNRTI plasma concentrations in the OFF period, patients maintained an undetectable viral load. The mechanistic explanation should be investigated.
Alectinib for relapsed or refractory anaplastic lymphoma kinase‐positive anaplastic large cell lymphoma: An open‐label phase II trial
Authors: Fukano Reiji , Mori Tetsuya , Sekimizu Masahiro , Choi Ilseung , Kada Akiko , Saito Akiko Moriya , Asada Ryuta , Takeuchi Kengo , Terauchi Takashi , Tateishi Ukihide , Horibe Keizo , Nagai Hirokazu
Published: October 2020

Anaplastic lymphoma kinase (ALK) inhibition is expected to be a promising therapeutic strategy for ALK‐positive malignancies. We aimed to examine the efficacy and safety of alectinib, a second‐generation ALK inhibitor, in patients with relapsed or refractory ALK‐positive anaplastic large cell lymphoma (ALCL). This open‐label, phase II trial included patients (aged 6 years or older) with relapsed or refractory ALK‐positive ALCL. Alectinib 300 mg was given orally twice a day (600 mg/d) for 16 cycles, and the duration of each cycle was 21 days. Patients who weighed less than 35 kg were given a reduced dose of alectinib of 150 mg twice a day (300 mg/d). Ten patients were enrolled, and the median age was 19.5 years (range, 6‐70 years). Objective responses were documented in eight of 10 patients (80%; 90% confidence interval, 56.2‐95.9), with six complete responses. The 1‐year progression‐free survival, event‐free survival, and overall survival rates were 58.3%, 70.0%, and 70.0%, respectively. The median duration of therapy was 340 days. No unexpected adverse events occurred. The most common grade 3 and higher adverse event was a decrease in neutrophil count in two patients. Alectinib showed favorable clinical activity and was well tolerated in patients with ALK‐positive ALCL who had progressed on standard chemotherapy. Based on the results of the current study, the Ministry of Health, Labour and Welfare of Japan approved alectinib for the treatment of recurrent or refractory ALK‐positive ALCL in February 2020.
Inhalation challenge test using pigeon eggs for chronic hypersensitivity pneumonitis
Authors: Okuda Ryo , Takemura Tamiko , Mikami Yu , Hagiwara Eri , Iwasawa Tae , Baba Tomohisa , Kitamura Hideya , Komatsu Shigeru , Okudela Koji , Ohashi Kenichi , Ogura Takashi
Published: October 2020

Background

Chronic hypersensitivity pneumonitis (CHP) remains a diagnostic challenge. The process of collecting and extracting serum and droppings from causative animals for the inhalation challenge test is complicated and the risk of inducing disease progression exists.

Objective

To investigate the utility and safety of an inhalation challenge test using pigeon eggs.

Methods

Pigeon eggs were pasteurized and mixed with a saline solution to produce an inhalation fluid. An inhalation challenge test was conducted on 19 patients with bird‐related CHP and 17 patients with interstitial lung disease other than bird‐related CHP. To identify antigens in pigeon eggs, the antigen‐antibody responses of the pigeon eggs and serum from patients were evaluated using Western blotting.

Results

The mean changes in C‐reactive protein, alveolar‐arterial oxygen difference, erythrocyte sedimentation rate, and lactate dehydrogenase significantly increased by 0.32 mg/dL (P = .014), 7.8 Torr (P = .002), 1.4 mm/h (P = .012), and 5.4 U/mL (P = .0019), respectively, in bird‐related CHP group compared to the control 24 hours after the inhalation challenge test. Furthermore, within 24 hours of the inhalation test, the mean forced vital capacity decreased by 2.3% in the bird‐related CHP group compared with a decline of 0.05% in the control group (P = .035). Serum collected from seven bird‐related CHP patients who underwent the inhalation challenge test and reacted to antigens with molecular weights of 37‐75 KDa, and these molecular weights were consistent with egg albumin and globulin.

Conclusion

Since a mild response was observed after the inhalation challenge test using pigeon eggs, this test was an obvious candidate for diagnosing bird‐related CHP.
Mutation analysis of tubulin beta 8 class VIII in infertile females with oocyte or embryonic defects
Authors: Yang Ping , Yin Changjian , Li Mei , Ma Shuiying , Cao Yongzhi , Zhang Changming , Chen Tailai , Zhao Han
Published: October 2020

Variants of tubulin beta 8 class VIII (TUBB8) have been shown to be associated with female infertility characterized by oocyte or embryonic defects. To further investigate the mutational spectrum of TUBB8 and the prevalence of variants, we performed Sanger sequencing of TUBB8 on a total of 115 infertile females who had undergone repeated in vitro fertilization cycles with oocyte or embryonic defects and 200 healthy controls. A total of 31 variants which were absent from the controls were identified in 36 unrelated individuals, accounting for a large proportion of this cohort (31.3%). All of the variants including heterozygous/homozygous missense variants and a heterozygous frameshift insertion variant were at conserved sites and predicted to be deleterious. Besides, these variants had diverse phenotypic effects, including not only oocyte maturation arrest, fertilization failure, and early embryonic arrest, but also multi‐pronuclei (MPN) formation, which is a new phenotype associated with TUBB8 variants. Overall, this study reveals a large number of variants of the TUBB8 gene in infertile females with oocyte or embryonic defects. Our results not only broaden the mutational and phenotypic spectra of TUBB8 variants, but also further confirm the critical role of TUBB8 in oocyte maturation, fertilization, and early embryonic development.
Exosomes from miRNA‐126‐modified endothelial progenitor cells alleviate brain injury and promote functional recovery after stroke
Authors: Wang Jinju , Chen Shuzhen , Zhang Wenfeng , Chen Yanfang , Bihl Ji C.
Published: October 2020

Aims

We previously showed that the protective effects of endothelial progenitor cells (EPCs)‐released exosomes (EPC‐EXs) on endothelium in diabetes. However, whether EPC‐EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EPC‐EXs on diabetic stroke mice and tested whether miR‐126 enriched EPC‐EXs (EPC‐EXsmiR126) have enhanced efficacy.

Methods

The db/db mice subjected to ischemic stroke were intravenously administrated with EPC‐EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase‐3, miR‐126, and VEGFR2 were measured on day 2 and 14.

Results

We found that (a) injected EPC‐EXs merged with brain endothelial cells, neurons, astrocytes, and microglia in the peri‐infarct area; (b) EPC‐EXsmiR126 were more effective than EPC‐EXs in decreasing infarct size and increasing CBF and MVD, and in promoting angiogenesis and neurogenesis as well as neurological functional recovery; (c) These effects were accompanied with downregulated cleaved caspase‐3 on day 2 and vascular endothelial growth factor receptor 2 (VEGFR2) upregulation till day 14.

Conclusion

Our results indicate that enrichment of miR126 enhanced the therapeutic efficacy of EPC‐EXs on diabetic ischemic stroke by attenuating acute injury and promoting neurological function recovery.
Benefits of protected areas for nonbreeding waterbirds adjusting their distributions under climate warming
Authors: Gaget Elie , Pavón‐Jordán Diego , Johnston Alison , Lehikoinen Aleksi , Hochachka Wesley M. , Sandercock Brett K. , Soultan Alaaeldin , Azafzaf Hichem , Bendjedda Nadjiba , Bino Taulant , Božič Luka , Clausen Preben , Dakki Mohamed , Devos Koen , Domsa Cristi , Encarnação Vitor , Erciyas‐Yavuz Kiraz , Faragó Sándor , Frost Teresa , Gaudard Clemence , Gosztonyi Lívia , Haas Fredrik , Hornman Menno , Langendoen Tom , Ieronymidou Christina , Kostyushin Vasiliy A. , Lewis Lesley J. , Lorentsen Svein‐Håkon , Luigujõe Leho , Meissner Włodzimierz , Mikuska Tibor , Molina Blas , Musilová Zuzana , Natykanets Viktor , Paquet Jean‐Yves , Petkov Nicky , Portolou Danae , Ridzoň Jozef , Sayoud Samir , Šćiban Marko , Sniauksta Laimonas , Stīpniece Antra , Strebel Nicolas , Teufelbauer Norbert , Topić Goran , Uzunova Danka , Vizi Andrej , Wahl Johannes , Zenatello Marco , Brommer Jon E.
Published: October 2020

Climate warming is driving changes in species distributions and community composition. Many species have a so‐called climatic debt, that is, shifts in range lag behind shifts in temperature isoclines. Inside protected areas (PAs), community changes in response to climate warming can be facilitated by greater colonization rates by warm‐dwelling species, but also mitigated by lowering extirpation rates of cold‐dwelling species. An evaluation of the relative importance of colonization‐extirpation processes is important to inform conservation strategies that aim for both climate debt reduction and species conservation. We assessed the colonization‐extirpation dynamics involved in community changes in response to climate inside and outside PAs. To do so, we used 25 years of occurrence data of nonbreeding waterbirds in the western Palearctic (97 species, 7071 sites, 39 countries, 1993–2017). We used a community temperature index (CTI) framework based on species thermal affinities to investigate species turnover induced by temperature increase. We determined whether thermal community adjustment was associated with colonization by warm‐dwelling species or extirpation of cold‐dwelling species by modeling change in standard deviation of the CTI (CTISD). Using linear mixed‐effects models, we investigated whether communities in PAs had lower climatic debt and different patterns of community change than communities outside PAs. For CTI and CTISD combined, communities inside PAs had more species, higher colonization, lower extirpation, and lower climatic debt (16%) than communities outside PAs. Thus, our results suggest that PAs facilitate 2 independent processes that shape community dynamics and maintain biodiversity. The community adjustment was, however, not sufficiently fast to keep pace with the large temperature increases in the central and northeastern western Palearctic. Our results underline the potential of combining CTI and CTISD metrics to improve understanding of the colonization‐extirpation patterns driven by climate warming.
The science behind programming algorithms for sacral neuromodulation
Authors: Knowles Charles H. , de Wachter Stefan , Engelberg Stefan , Lehur Paul , Matzel Klaus E. , Zirpel Lance ,   the European SNM Expert Group
Published: October 2020

Aim

Sacral neuromodulation (SNM) is a widely adopted treatment for overactive bladder, non‐obstructive urinary retention and faecal incontinence. In the majority, it provides sustained clinical benefit. However, it is recognized that, even for these patients, stimulation parameters (such as amplitude, electrode configuration, frequency and pulse width) may vary at both initial device programming and at reprogramming, the latter often being required to optimize effectiveness. Although some recommendations exist for SNM programming, the scientific data to support them are understood by few clinicians.

Methods

This is a narrative review of the literature covering some of the science behind stimulating a mixed peripheral nerve and available preclinical data in the field of SNM. It covers electrode configuration, amplitude, frequency, pulse width and cycling considerations. The review is targeted at clinicians with an interest in the field and does not seek to provide exhaustive detail on basic neuroscience.

Results and conclusions

Knowledge of the science of neuromodulation provides some guiding principles for programming but these are broad. These principles are not refuted by preclinical data but specific parameters in clinical use are not strongly supported by animal data, even after the limitations of small and large animal models are considered. The review presents a shortlist of programming principles on a theoretical basis but acknowledges that current practice is as much derived from evolved experience as science.
Impulse oscillometry and spirometry measurements relative to personal best values at the time of acute exacerbations of cystic fibrosis in adults
Authors: Blin Timothée , Flament Thomas , Mankikian Julie , Chambellan Arnaud , Marchand‐Adam Sylvain , Plantier Laurent
Published: October 2020

Background

Diagnosis of acute exacerbation (AE) of cystic fibrosis (CF) must be precise because both under‐ and over‐prescription of antibiotics may be detrimental. How lung function tests contribute to diagnose AE is unclear. We aimed to describe variation of spirometry and oscillometry measurements, at Stable state and at AE in adults with CF.

Methods

Patients were included in a retrospective single‐centre study when both spirometry (FEV1, FVC) and oscillometry (X5, R5, R5−R20 and AX) data were available for at least one Stable and one AE visit between December 2016 and July 2019. For each visit, we calculated variation (Δ) in spirometry and oscillometry indices in comparison with personal best values. Measurements were expressed as % of predicted values and Z‐scores when applicable. Areas under ROC curves (AUC) were computed.

Results

Forty‐two patients (28 ± 9 years, FEV1 64 ± 21%) were included; 80 AE and 104 Stable visits were analysed. FEV1 (L, %pred and Z‐score) and FVC (%pred and Z‐score) varied significantly between AE and Stable visits (p < .05), although differences were small (80 ml/2.7%pred for FEV1). Among oscillometry indices, X5 (kPa.s.L−1), R5–R20 (kPa.s.L−1) and AX (kPa/L) varied significantly. The AUCs for the variation in spirometry indices ranged from 0.601 (ΔFVC L) to 0.635 (ΔFEV1%pred). They were not significantly different from the AUCs for ΔX5 (0.589), ΔR5−R20 (0.649) and ΔAX (0.598).

Conclusions

Performance of both spirometry and oscillometry to discriminate AE from Stable state was poor. Variation of oscillometry indices (X5, R5−R20, AX) may be helpful when spirometry is unreliable or uncomfortable.
Fibrin glue injection: Rescue treatment for refractory post‐sphincterotomy and post‐papillectomy bleedings
Authors: Orlandini Beatrice , Schepis Tommaso , Tringali Andrea , Familiari Pietro , Boškoski Ivo , Borrelli de Andreis Federica , Perri Vincenzo , Costamagna Guido
Published: October 2020

Objectives

Endoscopic sphincterotomy (ES) and papillectomy (EP) are associated with a non‐negligible risk of post‐procedural bleeding. Despite first‐line endoscopic hemostasis being achieved by several methods, patients may experience bleeding persistence or recurrence. In such cases, fibrin glue (FG) injection may be used as a rescue therapy before more invasive approaches. The aim of this study was to evaluate the efficacy and safety of endoscopic FG injection to treat refractory post‐ES and post‐EP bleeding.

Methods

Data were collected retrospectively from patients with refractory immediate or delayed bleeding following ES or EP, between October 2007 and November 2019, at a single institution. Clinical success was defined as bleeding control after FG injection.

Results

Overall, 70 patients were included. Clinical success was reached in 64 (91.4%) patients after one session of FG injection. Of six (8.6%) patients in whom the treatment failed, one required subsequent insertion of a fully covered self‐expanding metal stent (FC‐SEMS) due to immediate massive bleeding, while five experienced bleeding recurrence. Such events were managed with an additional session of FG injection that failed in two cases. Therefore, one patient underwent FC‐SEMS plus selective embolization, whereas the other underwent diagnostic arteriography. No severe periprocedural complications occurred. Two cases of intrabiliary glue migration were treated by endoscopic removal with a retrieval basket.

Conclusions

Rescue therapy with endoscopic FG injection appears to be effective and safe to treat refractory post‐ES and post‐EP bleeding. Further studies are required to confirm these preliminary data.
Peri‐transplant glycaemic control as a predictor of pancreas transplant survival
Authors: Shapey Iestyn M. , Tan Zheng L. , Gioco Rossella , Khambalia Hussein , Fullwood Catherine , Yiannoullou Petros , Summers Angela , Hanley Neil A. , Augustine Titus , Rutter Martin K. , van Dellen David
Published: October 2020

Aims

The relationship between peri‐transplant glycaemic control and outcomes following pancreas transplantation is unknown. We aimed to relate peri‐transplant glycaemic control to pancreas graft survival and to develop a framework for defining early graft dysfunction.

Methods

Peri‐transplant glycaemic control profiles over the first 5 days postoperatively were determined by an area under the curve [AUC; average daily glucose level (mmol/L) × time (days)] and the coefficient of variation of mean daily glucose levels. Peri‐transplant hyperglycaemia was defined as an AUC ≥35 mmol/day/L (daily mean blood glucose ≥7 mmol/L). Risks of graft failure associated with glycaemic control and variability and peri‐transplant hyperglycaemia were determined using covariate‐adjusted Cox regression.

Results

We collected 7606 glucose readings over 5 days postoperatively from 123 pancreas transplant recipients. Glucose AUC was a significant predictor of graft failure during 3.6 years of follow‐up (unadjusted HR [95% confidence interval] 1.17 [1.06‐1.30], P = .002). Death censored non‐technical graft failure occurred in eight (10%) recipients with peri‐transplant normoglycaemia, and eight (25%) recipients with peri‐transplant hyperglycaemia such that hyperglycaemia predicted a 3‐fold higher risk of graft failure [HR (95% confidence interval): 3.0 (1.1‐8.0); P = .028].

Conclusion

Peri‐transplant hyperglycaemia is strongly associated with graft loss and could be a valuable tool guiding individualized graft monitoring and treatment. The 5‐day peri‐transplant glucose AUC provides a robust and responsive framework for comparing graft function.
Echocardiographic strain analysis reflects impaired ventricular function in youth with pediatric‐onset systemic lupus erythematosus
Authors: Chang Joyce C. , Wang Yan , Xiao Rui , Fedec Anysia , Meyers Kevin E. , Tinker Craig , Natarajan Shobha S. , Knight Andrea M. , Weiss Pamela F. , Mercer‐Rosa Laura
Published: October 2020

Background

Strain analysis with speckle‐tracking echocardiography shows promise as a screening tool for silent myocardial dysfunction in pediatric‐onset systemic lupus erythematosus (pSLE). We compared left ventricular (LV) systolic deformation (measured by strain) in children and adolescents with pSLE to controls, and assessed the relationship between strain, disease activity, and other noninvasive measures of cardiovascular health.

Methods

Twenty pSLE subjects ages 9–21 underwent comprehensive cardiovascular testing, including 2D speckle‐tracking echocardiography, ambulatory blood pressure monitoring (ABPM), peripheral endothelial function testing, pulse wave velocity and analysis, and carotid ultrasound. Longitudinal apical‐4 chamber (LSA4C) and midpoint circumferential strain (CSmid) were compared to that of 70 healthy controls using multivariable linear regression. Among pSLE subjects, Pearson correlation coefficients were calculated to evaluate relationships between global longitudinal or circumferential strain and other measures of cardiovascular health.

Results

Average SLE disease duration was 3.2 years (standard deviation [SD] 2.1). 2/20 pSLE subjects had persistent disease activity, and only one met criteria for hypertension by ABPM. LSA4C was significantly reduced in pSLE subjects compared to controls (mean −18.3 [SD 3.2] vs −21.8% [SD 2.2], P‐value <.001). There was no significant difference in CSmid (−24.8 [SD 3.7] vs −25.7% [SD 3.4], P = .29). Among pSLE subjects, decreased nocturnal blood pressure dipping on ABPM was associated with reduced global circumferential strain (r −0.59, P = .01).

Conclusions

Longitudinal myocardial deformation is impaired in pSLE patients despite clinical remission and may represent early myocardial damage. Strain analysis should be considered in addition to standard echocardiographic assessment during follow‐up of patients with pSLE.
Volatiles from the fungus Fusarium oxysporum affect interactions of Brassica rapa plants with root herbivores
Authors: Moisan Kay , Dicke Marcel , Raaijmakers Jos M. , Rachmawati Elvira , Cordovez Viviane
Published: October 2020

1. Soil is a diverse and heterogeneous environment where chemicals mediate numerous interactions between soil organisms and plants. To date, studies have extensively addressed volatile‐mediated interactions between soil microorganisms and the effects of microbial volatiles on plant growth. Yet, to our knowledge, it remains to be explored whether volatiles from soil‐borne fungi can influence plant interactions with root herbivores, facilitating or hampering performance of competitors that share the same host plant.

2. In the present study, we investigated the effects of volatiles emitted by the soil‐borne fungus Fusarium oxysporum on the performance of two root herbivores: the plant parasitic cyst nematode, Heterodera schachtii, and the insect root herbivore, Delia radicum, upon infestation of Brassica rapa roots.

3. Fungal volatiles slowed down the development of the root nematode cysts but increased their size, suggesting an enhanced egg load. In contrast, the performance of the insect root herbivore was unaffected by the exposure of roots to fungal volatiles. Additionally, fungal volatiles promoted the growth of plants infested with the root nematode, but not of those infested with the insect root herbivore.

4. Together, our data show that volatiles from a soil‐borne fungus can affect root interactions with root herbivores. Increased production of nematode eggs and plant growth promotion suggest a specific modulation of root‐herbivore interactions by fungal volatiles.
Deciding Fast: Examining the Relationship between Strategic Decision Speed and Decision Quality across Multiple Environmental Contexts
Authors: Shepherd Neil Gareth , Mooi Erik A. , Elbanna Said , Rudd John M.
Published: October 2020

Rapid innovation, shortened product life cycles and fierce competition place great pressures on top managers to make fast strategic decisions. However, a key question in strategic decision‐making research is whether decision speed helps or harms decision quality, and there is a shortage of theory and evidence concerning the consequences of decision speed across different environmental contexts. We develop new theory by considering the effects of decision speed on decision quality under conditions of environmental munificence, under conditions of dynamism, and under the joint conditions of munificence and dynamism. We test our theory through analysis of multi‐informant survey data drawn from top management teams and secondary databases, in 117 UK firms. Our findings demonstrate that munificence is the central generative mechanism which moderates the relationship between decision speed and decision quality, and markedly alters the previously theorized positive effects of decision speed in dynamic contexts.
SASP‐induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis
Authors: Ogata Yuichiro , Yamada Takaaki , Hasegawa Seiji , Sanada Ayumi , Iwata Yohei , Arima Masaru , Nakata Satoru , Sugiura Kazumitsu , Akamatsu Hirohiko
Published: October 2020

Recently, increasing attention has been paid to senescence‐associated secretory phenotype (SASP), a phenomenon that senescent cells secrete molecules such as inflammatory cytokines and matrix metalloproteinases (MMPs), due to its noxious effects on the surrounding tissue. Senescent cells in the blood and liver are known to be properly depleted by macrophages. In the dermis, accumulation of senescent cells has been reported and is thought to be involved with skin ageing. In this study, to elucidate the clearance mechanism of senescent cells in the dermis, we focused on macrophage functions. Our co‐culture experiments of senescent fibroblasts and macrophages revealed a two‐step clearance mechanism: first, TNF‐α secreted from macrophages induces apoptosis in senescent fibroblasts, and then, dead cells are phagocytosed by macrophages. Furthermore, it was suggested that SASP factors suppress both of the two steps of the senescent cell clearance by macrophages. From these findings, normally senescent cells in the dermis are thought to be removed by macrophages, but when senescent cells are excessively accumulated owing to oxidative stress, ultraviolet (UV) ray or other reasons, SASP was suggested to suppress the macrophage‐dependent clearance functions and thereby cause further accumulation of senescent cells.
IL‐23 modulates histamine‐evoked itch and responses of pruriceptors in mice
Authors: Pavlenko Darya , Funahashi Hideki , Sakai Kent , Hashimoto Takashi , Lozada Taisa , Yosipovitch Gil , Akiyama Tasuku
Published: October 2020

Accumulating evidence has highlighted the essential roles of cytokines in itch processing. Although IL‐23 and Th17 cytokines are elevated in inflammatory skin disorders, their role in itch is unknown. Here, we investigated the role of IL‐23 and IL‐17A in itch response using an in vitro calcium imaging of mouse dorsal root ganglion (DRG) neurons and an in vivo behaviour test. Calcium imaging studies revealed that a few DRG neurons (~5%) responded to either IL‐23 or IL‐17A. Pretreatment cells with IL‐23 significantly reduced calcium responses to histamine and capsaicin but not chloroquine. Behaviour experiments showed neither IL‐23 nor IL‐17A evoked scratching. IL‐23 significantly decreased histamine‐evoked scratching without affecting chloroquine‐evoked scratching. There was no difference in scratching between IL‐17A‐ and vehicle‐treated groups. These results indicate that IL‐23 might play a role in regulating histaminergic itch via modulation of TRPV1 activity.
Burden and Treatment Satisfaction among Caregivers of Adolescents with Borderline Personality Disorder
Authors: Jørgensen Mie Sedoc , Storebø Ole Jakob , Poulsen Stig , Simonsen Erik
Published: October 2020

Despite the fact that family involvement is encouraged in early interventions for borderline personality disorder (BPD), there is a limited knowledge on the experience of caring for adolescents with BPD. This is an exploratory retrospective study nested within a randomized controlled trial that compared mentalization‐based treatment (MBT) in groups to treatment as usual for adolescents with BPD. Caregivers received six MBT‐Parents sessions or standard care over one year. Three months after end of treatment (EOT), 75 caregivers (35 in MBT, 40 in TAU) filled out the Burden Assessment Scale, and 71 (34 in MBT, 37 in TAU) the Family Satisfaction Survey. The adolescents filled out the Borderline Personality Features Scale for Children at baseline and after twelve months at EOT. We tested whether caregiver demographics, adolescents’ severity of BPD, treatment and adolescents’ dropout from treatment predicted levels of caregiver burden and satisfaction with treatment. The caregivers reported high levels of burden on the BAS (M = 40.3, SD = 12.2). Our study suggests that higher BPD severity at EOT among the adolescents predicted caregiver burden (p = .03), whereas higher baseline BPD severity predicted satisfaction with treatment (p = .04) and that biological mothers could be more burdened than other types of caregivers but also might be more satisfied with treatment. Treatment and adolescents’ dropout from treatment were not related to caregiver burden or satisfaction with treatment. To help inform future research and to devise appropriate interventions for caregivers and adolescents with BPD, it is important to identify possible predictors of caregiver burden. The results of this initial exploratory study indicate that caregivers (and particularly biological mothers) of adolescents with more severe levels of BPD could be particularly vulnerable toward feelings of burden and therefore are in need of support.
Clinical Oral Disorders in Adults Screening Protocol (CODA‐SP) from the 2019 Vancouver IADR Consensus Symposium
Authors: MacEntee Michael I. , Brondani Mario , Avivi‐Arber Limor , Bartlett David , Donnelly Leeann , Duyck Joke , Hori Kazuhiro , Karve Avanti , Persson G. Rutger , Kettratad‐Pruksapong Matana , Schimmel Martin , Hon‐ching So Frankie , Thomson W. Murray , Yoon Minn N. , Wyatt Chris
Published: October 2020

Background

The Clinical Oral Disorder in Elders (CODE) index was proposed in 1999 to assess the oral health status and treatment needs of older people who typically were edentate or had few natural teeth. Since then, more people are retaining natural teeth into old age and have oral disorders similar to younger adults. In addition, there has been further guidance on screening for disease that includes changes to the clinical indicators of several oral disorders and greater sensitivity to people's concerns about their oral health and care needs.

Methods

Experts in dental geriatrics assembled at a satellite symposium of the International Association of Dental Research in June 2019 to revise the objectives and content of the CODE index. Before the symposium, 139 registrants were asked for comments on the CODE index, and 11 content experts summarised current evidence and assembled reference lists of relevant information on each indicator. The reference lists provided the base for a narrative review of relevant evidence supplemented by reference tracking and direct searches of selected literature for additional evidence.

Results

Analysis of the evidence by consensus of the experts produced the Clinical Oral Disorders in Adults Screening Protocol (CODA‐SP).

Conclusions

The CODA‐SP encompasses multiple domains of physical and subjective indicators with weighted severity scores. Field tests are required now to validate its effectiveness and utility in oral healthcare services, outcomes and infrastructure.
Calf circumference and risk of cardiovascular disease
Authors: Hsiang Chih‐Hsuan , Wu Chen‐Jung , Kao Tung‐Wei , Chen Wei‐Liang
Published: October 2020

Aim

Calf circumference (CC) is an anthropometric parameter that is easily obtained. Increasingly, research has shown that CC related to cardiovascular events. We aimed to determine the correlation between CC and Framingham risk score (FRS) for the 10‐year cardiovascular disease risk assessment in Taiwanese elderly aged ≥65 years.

Methods

We included 540 men and 683 women aged ≥65 years. All participants and data were collected from geriatric physical screenings in Tri‐Service General Hospital in Taiwan during 2017. The correlation between CC and FRS‐coronary heart disease (CHD) were calculated. We used multivariate regression models to investigate the correlation between CC and FRS‐CHD. Covariate adjustments were investigated by performing an extended model.

Results

A significantly negative association was observed between FRS‐CHD and CC in both genders in both models (all P < 0.05). Male and female participants were divided into quartiles at the CC level (Q1–Q4) and we compared their baseline characteristics separately. We further explored the association between CC divided in quartiles and the FRS‐CHD, which exhibited a significant negative correlation comparing the largest quartiles with the first quartile in a fully adjusted model in both genders (P < 0.05). In addition, the higher quartiles of CC seemed to have a lower FRS‐CHD with statistical significance (P for trend <0.05).

Discussion

CC had a strongly negative correlation with FRS‐CHD in both genders. In the future, CC might be an applicable tool in geriatric research in Taiwan for the early detection of developing cardiovascular events. Geriatr Gerontol Int 2020; 20: 1133–1137.
Migraine and Headache Care in the Republic of Ireland: History and a Vision for the Future Influenced by the COVID‐19 Pandemic
Authors: Tomkins Esther , Craven Audrey , Ruttledge Martin
Published: October 2020

Background

The care and management of migraine/headache patients in the Republic of Ireland over the last 25 years are summarized in this article.

Methods

Collaboration between voluntary patient organizations (the Migraine Association of Ireland or MAI), primary care services, and hospital/community shared healthcare professionals (most notably the headache specialist nurse), is highlighted as one of the key features of this management strategy in an underfunded and under‐resourced public healthcare system.

Conclusion

The migraine/headache community in Ireland is small, but they have been dedicated in their commitment to improving care for their patients for more than 2 decades. As a result, they have been successful in recent years, both nationally and internationally, in terms of financial funding and support for their multidisciplinary and collaborative approach.