bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermediate Skin Substitutes Are Unnecessary in Small (<10% TBSA) Burns
Authors: Lacey Alexandra Michelle , Maniago Ellen , Gillenwater Timothy Justin , Yenikomshian Haig , Garner Warren Louis
Published: June 2020

The use of intermediate skin substitutes between debridement and final autografting is routine for many practitioners. Materials such as xenografts and allografts have been promoted to help with wound coverage before autografting. However, there is limited data for their use in relatively small burn wounds (<10% TBSA). In this study, we analyzed the outcomes of 100 consecutive patients who underwent autografting for burns <10% TBSA at our American Burn Association-verified burn unit in the absence of intermediate skin substitute use. We retrospectively analyzed 100 patients who underwent split thickness skin graft autografting for burns <10% TBSA between November 2017 and June 2019. No patients were treated with intermediate skin substitutes. Analysis included basic demographics, comorbidities, TBSA burned, mechanism of burn, time to grafting, if grafting was performed in a single procedure or staged, graft loss (>50% graft failure), and time to complete healing (no further wound care required). Twelve patients (12%) had unpredictable graft beds, and their procedure was staged. These patients underwent surgical debridement and were dressed in antimicrobial dressing for an average of 5 days before autografting. No patients had intermediate skin substitutes between procedures. Eighty-eight patients (88%) were debrided and grafted in a single stage. In the staged group, there was a 0% rate of graft failure compared with 9.1% rate of graft failure in the primarily grafted group (P = .004). There was a similar length of stay and time to complete healing in the staged group and primarily grafted group (P = .496 and P = .571). There was a significantly shorter time from injury to first procedure between the staged group and the primarily grafted group (8.7 days and 13.5 days, P = .014). In the eight instances of graft failure, infection or inadequate debridement was the cause. Seven of these eight cases required further surgical intervention. Intermediate skin substitutes are an unnecessary step in grafting small burns. These add only complexity and cost to patient care. Many patients can be debrided and grafted in a single stage. Debridement alone with delayed grafting is a highly effective surgical method when the wound bed is not suitable for immediate grafting. The use of intermediate skin substitutes in small burns requires further investigation as this study finds low benefit for this product.
Re-collecting Cypriot antiquity: the Kent collection in Harrogate
Authors: Reeve Anna , Waite Sally
Published: June 2020

Formed by the Kent family – farmers and landowners from the north of England – the little-known Kent collection brought together antiquities from Greece, Rome, Egypt and Cyprus, alongside weapons, armour, furniture and textiles. On the death of Benjamin Kent in 1968, most of the collection was bequeathed to the Harrogate Corporation, sparking debate on the value of such heterogeneous collections for general public audiences. This article investigates the collection’s history, examining the practices that formed it, the quasi-museum setting of the Kent family home, and the collection’s display following its transfer to municipal ownership. We focus on the ancient Cypriot objects, some of which can be traced to Thomas Backhouse Sandwith, British vice-consul on Cyprus from 1865 to 1870 and an important figure in the early collecting of Cypriot antiquities in the UK. Through this exploration, we consider how histories of collections, especially smaller-scale collections of private individuals, can re-contextualize objects and enrich their interpretation.
The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32
Authors: Pimentel Isabel , Chen Bingshu E , Lohmann Ana Elisa , Ennis Marguerite , Ligibel Jennifer , Shepherd Lois , Hershman Dawn L , Whelan Timothy , Stambolic Vuk , Mayer Ingrid , Hobday Timothy , Lemieux Julie , Thompson Alastair , Rastogi Priya , Gelmon Karen , Rea Daniel , Rabaglio Manuela , Ellard Susan , Mates Mihaela , Bedard Philippe , Pitre Lacey , Vandenberg Theodore , Dowling Ryan J O , Parulekar Wendy , Goodwin Pamela J
Published: June 2020

Background

Metformin has been associated with lower breast cancer (BC) risk and improved outcomes in observational studies. Multiple biologic mechanisms have been proposed, including a recent report of altered sex hormones. We evaluated the effect of metformin on sex hormones in MA.32, a phase III trial of nondiabetic BC subjects who were randomly assigned to metformin or placebo.

Methods

We studied the subgroup of postmenopausal hormone receptor-negative BC subjects not receiving endocrine treatment who provided fasting blood at baseline and at 6 months after being randomly assigned. Sex hormone-binding globulin, bioavailable testosterone, and estradiol levels were assayed using electrochemiluminescence immunoassay. Change from baseline to 6 months between study arms was compared using Wilcoxon sum rank tests and regression models.

Results

312 women were eligible (141 metformin vs 171 placebo); the majority of subjects in each arm had T1/2, N0, HER2-negative BC and had received (neo)adjuvant chemotherapy. Mean age was 58.1 (SD=6.9) vs 57.5 (SD=7.9) years, mean body mass index (BMI) was 27.3 (SD=5.5) vs 28.9 (SD=6.4) kg/m2 for metformin vs placebo, respectively. Median estradiol decreased between baseline and 6 months on metformin vs placebo (−5.7 vs 0 pmol/L; P < .001) in univariable analysis and after controlling for baseline BMI and BMI change (P < .001). There was no change in sex hormone-binding globulin or bioavailable testosterone.

Conclusion

Metformin lowered estradiol levels, independent of BMI. This observation suggests a new metformin effect that has potential relevance to estrogen sensitive cancers.
Brain Iron Accumulation and the Formation of Calcifications After Developmental Zika Virus Infection
Authors: Snyder-Keller Abigail , Bolivar Valerie J , Zink Steven , Kramer Laura D
Published: June 2020

Intracranial calcifications (ICC) are the most common neuropathological finding in the brains of children exposed in utero to the Zika virus (ZIKV). Using a mouse model of developmental ZIKV infection, we reported widespread calcifications in the brains of susceptible mice that correlated in multiple ways with the behavioral deficits observed. Here, we examined the time course of ICC development and the role of iron deposition in this process, in 3 genetically distinct inbred strains of mice. Brain iron deposits were evident by Perls’ staining at 2 weeks post infection, becoming increasingly dense and coinciding with calcium buildup and the formation of ICCs. A regional analysis of the brains of susceptible mice (C57BL/6J and 129S1/SvImJ strains) revealed the presence of iron initially in regions containing many ZIKV-immunoreactive cells, but then spreading to regions containing few infected cells, most notably the thalamus and the fasciculus retroflexus. Microglial activation was widespread initially and later delineated the sites of ICC formation. Behavioral tests conducted at 5–6 weeks of age revealed greater deficits in mice with the most extensive iron deposition and calcification of subcortical regions, such as thalamus. These findings point to iron deposition as a key factor in the development of ICCs after developmental ZIKV infection.
Is Next-Generation Sequencing Alone Sufficient to Reliably Diagnose Gliomas?
Authors: Kam Kwok Ling , Appin Christina L , Mao Qinwen , Ikegami Sachie , Lukas Rimas V , Nikiforova Marina N , Roy Somak , Brat Daniel J , Horbinski Craig
Published: June 2020

The power and widespread use of next-generation sequencing (NGS) in surgical neuropathology has raised questions as to whether NGS might someday fully supplant histologic-based examination. We therefore sought to determine the feasibility of relying on NGS alone for diagnosing infiltrating gliomas. A total of 171 brain lesions in adults, all of which had been analyzed by GlioSeq NGS, comprised the study cohort. Each case was separately diagnosed by 6 reviewers, based solely on age, sex, tumor location, and NGS results. Results were compared with the final integrated diagnoses and scored on the following scale: 0 = either wrong tumor type or correct tumor type but off by 2+ grades; 1 = off by 1 grade; 2 = exactly correct. Histology alone was treated as a seventh reviewer. Overall reviewer accuracy ranged from 81.6% to 94.2%, while histology alone scored 87.1%. For glioblastomas, NGS was more accurate than histology alone (93.8%–97.9% vs 87.5%). The NGS accuracy for grade II and III astrocytoma and oligodendroglioma was only 54.3%–84.8% and 34.4%–87.5%, respectively. Most uncommon gliomas, including BRAF-driven tumors, could not be accurately classified just by NGS. These data indicate that, even in this era of advanced molecular diagnostics, histologic evaluation is still an essential part of optimal patient care.
Teenage Tachypnea
Authors: Croskerry Pat
Published: June 2020

This case involves a young woman sent from a psychiatric hospital to the emergency department for assessment. Her chief complaint is intermittent shortness of breath. According to the psychiatrist’s note, she has experienced frequent episodes of uncontrollable hyperventilation, associated with carpopedal spasm and loss of consciousness in the past. There is concern she may have a chest infection. A chest X-ray appears to exclude a chest infection as an explanation of her symptoms, and arrangements are made to transfer her back to the psychiatric facility with a diagnosis of exacerbation of anxiety state. Unexpectedly, there is a sudden deterioration in the patient’s condition, which proves fatal.
The English Patient
Authors: Croskerry Pat
Published: June 2020

This case discusses a stoical Englishman who presents to the emergency department of a community hospital in the early hours of the morning with a complaint of headache. The emergency physician makes a diagnosis of migraine and decides to keep the patient overnight to ensure he settles okay. He plans on discharging the patient when he is awake. In the morning, the patient is assessed by a second emergency physician, who discovers a different diagnosis. The case highlights several major biases that may have been compounded by sleep deprivation and fatigue. The concept of manifestness of disease is introduced together with a general discussion of how this feature may impact the recognition of a particular diagnosis.
A Rash Diagnosis
Authors: Croskerry Pat
Published: June 2020

This case presents a 16-year-old female with complaints of headache, abdominal pain, diarrhea, and vomiting who is brought to the emergency department by her parents. The emergency physician is struck by a petechial rash on the patient’s face, which triggers a vivid memory of a similar rash in a patient with meningococcemia that proved fatal. A lumbar puncture is quickly done, and antibiotics are initiated. The patient is subsequently transferred to another physician, who finds an alternate explanation for the patient’s symptoms and refers her to surgery.
Basaglia’s legacy and Italian mental healthcare today
Authors: Fioritti Angelo
Published: June 2020

After Law 180 of 1978, universally known as ‘Basaglia Law’, Italy started a process of progressive closure of all mental hospitals and the establishment of a community mental healthcare system. Dehospitalization was completed in 1997, whilst the development of community services has continued over the last 40 years. Today, mental healthcare in Italy is within the National Health System, with liberal regulations on coercion and the lowest number of beds in general hospitals and residential facilities. However, the last decade has seen many threats challenging the system, mostly due to rapid social changes and to the financial consequences of the economic crisis. This chapter analyses the accomplishments and pitfalls of the reform process and discusses how Basaglia’s vision may continue to further the development of mental healthcare services in Italy.
The optimism of practice
Authors: Venturini Ernesto , Brandão Goulart Maria Stella , Amarante Paulo
Published: June 2020

Basaglia’s impact in Brazil has been very significant not only in social and healthcare, but also in the world of culture, art, politics, and science. Two aspects can help us to assess this impact: the law of psychiatry reform, and the popularity of Basaglia among activist patients and mental health workers. To evaluate the background to this influence, this chapter refers to three key things: Basaglia’s trips to Brazil, as documented and according to the memory of witnesses; the published book of the talks of the meetings; and the invitation expressed by Basaglia to directly know the practice of Trieste. Finally, in order to analyse the reasons for the impact, the chapter refers to the strength of collective thought, the power of critical thinking, the focus on whole life, and great communicative ability. It concludes that Basaglia’s thoughts are, at the same time, radical and democratic.
‘Visions of another world’
Authors: Marazia Chantal , Fangerau Heiner , Becker Thomas , Söhner Felicitas
Published: June 2020

This chapter explores Franco Basaglia’s relation with German psychiatry, from his early infatuation with the anthropo-phenomenological tradition to the disputes with the social psychiatric movement during the 1960s and 1970s. After an overview of Basaglia’s criticism of German psychiatric schools and institutions, the chapter focuses on his personal links, most notably with progressive psychiatrists and with the anti-psychiatric movement SPK (Sozialistisches Patientenkollektiv). Finally, it analyses Basaglia’s reception, by both the medical establishment and the actors of psychiatric reform. Contrary to the current narrative of a mutual influence, the chapter argues that Basaglia can hardly be regarded as a genuine inspiration for German psychiatric reform, and was retrospectively refashioned as such.
Borderline deinstitutionalization
Authors: Flaker Vito , Jović Vladimir , Jović Nataša Cvetković , Rafaelič Andreja
Published: June 2020

The geographical vicinity of Trieste and Gorizia yielded only a borderline effect of deinstitutionalization in Yugoslavia. After initial interest, Yugoslav official psychiatry assumed a rejecting attitude covering the void of their failing project of ‘social psychiatry’. Anti-institutional and anti-authoritarian social movements embraced the ideas and praxis born on the border, to make deinstitutionalization a part of the democratization process. Trieste was a paragon for the first community services and deinstitutionalization attempts during and after the war and ‘transition’. The Italian model of transformation was often an effective corrective to top–down, culturally invasive ways in deinstitutionalization ‘hiccups’ in post-Yugoslav countries. Basaglian conceptual triangulation of structural, existential, and interactionist facets, pragmatic interinstitutional politics, a ‘conversion model’ of transformation, and an open-coded, radically humanist approach to people’s distress still resound in the deinstitutionalization praxis in the former Yugoslavia. Even if deinstitutionalization nowadays seems to be primarily technological, it still needs to be contextualized, not only locally but also in terms of global social and political challenges.
Galaxy And Mass Assembly (GAMA): assimilation of KiDS into the GAMA database
Authors: Bellstedt Sabine , Driver Simon P , Robotham Aaron S G , Davies Luke J M , Bogue Kamran R J , Cook Robin H W , Hashemizadeh Abdolhosein , Koushan Soheil , Taylor Edward N , Thorne Jessica E , Turner Ryan J , Wright Angus H
Published: June 2020

The Galaxy And Mass Assembly Survey (GAMA) covers five fields with highly complete spectroscopic coverage (>95 per cent) to intermediate depths (r < 19.8 or i < 19.0 mag), and collectively spans 250 deg2 of equatorial or southern sky. Four of the GAMA fields (G09, G12, G15, and G23) reside in the European Southern Observatory (ESO) VST KiDS and ESO VISTA VIKING survey footprints, which combined with our GALEX, WISE, and Herschel data provide deep uniform imaging in the $FUV/NUV/u/g/r/i/Z/Y/J/H/K_s/W1/W2/W3/W4/P100/P160/S250/S350/S500$ bands. Following the release of KiDS DR4, we describe the process by which we ingest the KiDS data into GAMA (replacing the SDSS data previously used for G09, G12, and G15), and redefine our core optical and near-infrared (NIR) catalogues to provide a complete and homogeneous data set. The source extraction and analysis is based on the new ProFound image analysis package, providing matched-segment photometry across all bands. The data are classified into stars, galaxies, artefacts, and ambiguous objects, and objects are linked to the GAMA spectroscopic target catalogue. Additionally, a new technique is employed utilizing ProFound to extract photometry in the unresolved MIR–FIR regime. The catalogues including the full FUV–FIR photometry are described and will be fully available as part of GAMA DR4. They are intended for both standalone science, selection for targeted follow-up with 4MOST, as well as an accompaniment to the upcoming and ongoing radio arrays now studying the GAMA 23h field.
Passive spirals and shock influenced star formation in the merging cluster A3376
Authors: Kelkar Kshitija , Dwarakanath K S , Poggianti Bianca M , Moretti Alessia , Monteiro-Oliveira Rogério , Machado Rubens E G , Lima-Neto Gastão B , Fritz Jacopo , Vulcani Benedetta , Gullieuszik Marco , Bettoni Daniela
Published: June 2020

We present a detailed analysis of star formation properties of galaxies in a nearby (z ∼ 0.046) young (∼0.6 Gyr) post-merger cluster system A3376, with a moderate merger shock front (vs ∼1630 km s−1; $\mathcal {M}$ ∼ 2) observed as symmetric radio relics. Exploiting the spectroscopic data from the wide-field OmegaWINGS survey and the associated photometric information, our investigations reveal the plausible effects of the dynamic post-merger environment differing from the high-density cluster environment experienced prior to the merging activity. The remnants of the pre-merger relaxed cluster environment are realized through the existence of passive spiral galaxies located in the central regions of the cluster between the two brightest cluster galaxies. We discover A3376 to contain a population of massive (log (M*/M⊙) > 10) blue regular star-forming spirals in regions of maximum merger shock influence but exhibiting star formation rates similar to those in relaxed clusters at similar epoch. We further discover low-mass (log (M*/M⊙) ≤ 10) late-type blue post-starburst galaxies which could either be formed as a result of rapid quenching of low-mass spirals following the shock-induced star formation or due to the intense surge in the intracluster medium pressures at the beginning of the merger. With the possibility of the merger shock affecting high- and low-mass spirals differently, our results bridge the seemingly contradictory results observed in known merging cluster systems so far and establish that different environmental effects are at play right from pre- to post-merger stages.
TESS photometry of helium-rich hot subdwarfs: r modes in BD+37°442 and BD+37°1977
Authors: Jeffery C Simon
Published: June 2020

Transiting Exoplanet Survey Satellite photometry of the extremely helium-rich hot subdwarfs BD+37°442 and BD+37°1977 demonstrates multiperiodic low-amplitude variability with principal periods of 0.56 and 1.14 d, respectively, and with both first and second harmonics present. The light curves are not perfectly regular, implying additional periodic and/or non-periodic content. Possible causes are examined, including the binary hypothesis originally introduced to explain X-ray observations, differentially rotating surface inhomogeneities, and pulsations. If the principal photometric periods correspond to the rotation periods, the stars are rotating at approximately 0.7 and 0.3 × break-up, respectively. Surface Rossby waves (r modes) therefore provide the most likely solution.
AP-endonuclease 1 sculpts DNA through an anchoring tyrosine residue on the DNA intercalating loop
Authors: Hoitsma Nicole M , Whitaker Amy M , Beckwitt Emily C , Jang Sunbok , Agarwal Pratul K , Van Houten Bennett , Freudenthal Bret D
Published: June 2020

Base excision repair (BER) maintains genomic stability through the repair of DNA damage. Within BER, AP-endonuclease 1 (APE1) is a multifunctional enzyme that processes DNA intermediates through its backbone cleavage activity. To accomplish these repair activities, APE1 must recognize and accommodate several diverse DNA substrates. This is hypothesized to occur through a DNA sculpting mechanism where structural adjustments of the DNA substrate are imposed by the protein; however, how APE1 uniquely sculpts each substrate within a single rigid active site remains unclear. Here, we utilize structural and biochemical approaches to probe the DNA sculpting mechanism of APE1, specifically by characterizing a protein loop that intercalates the minor groove of the DNA (termed the intercalating loop). Pre-steady-state kinetics reveal a tyrosine residue within the intercalating loop (Y269) that is critical for AP-endonuclease activity. Using X-ray crystallography and molecular dynamics simulations, we determined the Y269 residue acts to anchor the intercalating loop on abasic DNA. Atomic force microscopy reveals the Y269 residue is required for proper DNA bending by APE1, providing evidence for the importance of this mechanism. We conclude that this previously unappreciated tyrosine residue is key to anchoring the intercalating loop and stabilizing the DNA in the APE1 active site.
Factors influencing the efficacy of nutritional interventions on muscle mass in older adults: a systematic review and meta-analysis
Authors: Martin-Cantero Aitana , Reijnierse Esmee M , Gill Benjamin M T , Maier Andrea B
Published: June 2020

Context

Nutritional interventions stimulate muscle protein synthesis in older adults. To optimize muscle mass preservation and gains, several factors, including type, dose, frequency, timing, duration, and adherence have to be considered.

Objective

This systematic review and meta-analysis aimed to summarize these factors influencing the efficacy of nutritional interventions on muscle mass in older adults.

Data Sources

A systematic search was performed using the electronic databases MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and SPORTDiscus from inception date to November 22, 2017, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included randomized controlled trials, mean or median age ≥65 years, and reporting muscle mass at baseline and postintervention. Exclusion criteria included genetically inherited diseases, anabolic drugs or hormone therapies, neuromuscular electrical stimulation, chronic kidney disease, kidney failure, neuromuscular disorders, and cancer.

Data Extraction

Extracted data included study characteristics (ie, population, sample size, age, sex), muscle mass measurements (ie, method, measure, unit), effect of the intervention vs the control group, and nutritional intervention factors (ie, type, composition, dose, duration, frequency, timing, and adherence).

Data Analysis

Standardized mean differences and 95%CIs were calculated from baseline to postintervention. A meta-analysis was performed using a random-effects model and grouped by the type of intervention.

Conclusions

Twenty-nine studies were included, encompassing 2255 participants (mean age, 78.1 years; SD, 2.22). Amino acids, creatine, β-hydroxy-β-methylbutyrate, and protein with amino acids supplementation significantly improved muscle mass. No effect was found for protein supplementation alone, protein and other components, and polyunsaturated fatty acids. High interstudy variability was observed regarding the dose, duration, and frequency, coupled with inconsistency in reporting timing and adherence. Overall, several nutritional interventions could be effective to improve muscle mass measures in older adults. Because of the substantial variability of the intervention factors among studies, the optimum profile is yet to be established.

Systematic Review Registration

PROSPERO registration no. CRD42018111306.
External Fixation Devices Within the Magnetic Resonance Imaging Bore: A Safety and Radiologic Analysis
Authors: Ryan Scott , Moon Andrew S. , Gordon Matthew , Flacke Sebastian , Soni Shalin , Salzler Matthew J. , Stelma Sarah , Marcantonio Andrew
Published: June 2020

Objectives:

To (1) report the thermal changes encountered at the pin/skin interface in a cadaver with a knee-spanning external fixator inside the magnetic resonance imaging (MRI) bore and (2) report on the quality of the MRI sequences collected.

Methods:

Three commonly used external fixation systems were placed on cadaveric lower extremities to simulate knee external fixation. Fiber optic thermal probes were placed at the pin/skin interface of a femoral and tibial pin. A control probe was embedded in the soft tissues of the thigh. Full knee MRI scans were performed using a 1.5-Tesla magnet. Real-time thermal data were collected. A clinically significant increase in temperature compared with the control was defined as 2°C. Two blinded radiologists evaluated the images for image quality and overall diagnostic utility using a standardized 5-point grading scale.

Results:

There were statistically significant differences in the temperature changes between the femoral/tibial pin sites and the control probe sites during each phase of the MRI scan. However, there was only one clinically significant difference in temperature change during a single sequence of one MRI scan of one of the external fixator devices. Overall image quality was graded as a 4 for each image set with 100% interobserver agreement (k = 1.0).

Conclusions:

Despite significant differences in temperature changes between the pin sites and controls over multiple MRI sequences in commonly used external fixator devices, the differences in temperature change are likely not clinically relevant. Overall image quality and interpretability of the images were excellent.
Medical treatment of advanced malignant perivascular epithelioid cell tumors
Authors: Fabbroni Chiara , Sbaraglia Marta , Sanfilippo Roberta
Published: June 2020

Purpose of review

Malignant PEComa are rare mesenchymal tumors characterized by genetic alterations actionable by target therapy. Indeed, they harbour loss of function of TSC1/TSC2, which lead to the activation of the mammalian target of rapamycin (mTOR) pathway, which is targetable therapeutically with mTOR inhibitors like sirolimus. A small subset of malignant PEComas instead harbor TFE3 gene fusions known to be mutually exclusive with TSC1/TSC2 loss-of-function mutations; therefore, leading to different therapeutic implication.

Recent findings

mTOR inhibitors showed a response rate around 40% with a median PFS of 9 months both in retrospective case series than in phase 2 prospective clinical trials, therefore, representing the most active therapeutic drug. Up to now, the issue is the lack of further therapeutic lines in the advanced setting. Chemotherapy has a marginal role, while some responses were reported using Vascular endothelial growth factor-Tyrosine kynase inhibitors (VEGF-TKI) inhibitors.

Malignant PEComas display some sensitivity to mTOR inhibitors. If progression thereto, no other drugs are available. Preclinical studies are ongoing to explore the potential combination of hormonal blockade in women and the potential use of PD1 checkpoint inhibitors.
Impact of Pain, Opioids, and the Mu-opioid Receptor on Progression and Survival in Patients With Newly Diagnosed Stage IV Pancreatic Cancer
Authors: Steele Grant L. , Dudek Arkadiusz Z. , Gilmore Grace E. , Richter Sara A. , Olson Douglas A. , Eklund Justin P. , Zylla Dylan M.
Published: June 2020

Objectives:

Pancreatic adenocarcinoma is frequently associated with pain requiring opioid therapy. Opioids, however, have been implicated in causing tumor progression, ultimately shortening survival. We examined the impact of pain, opioid use, and the mu-opioid receptor (MOP-R) expression in tumor tissue on progression-free survival and overall survival of patients with metastatic pancreatic cancer.

Methods:

We identified 103 patients with metastatic pancreatic adenocarcinoma receiving chemotherapy and abstracted data from Tumor Registry, in addition to pain, opioid exposure, carbohydrate antigen 19-9 values, survival, and imaging response. MOP-R expression was evaluated using an immunohistochemistry assay. The association of variables with progression-free survival and overall survival was analyzed in univariate and multivariate models.

Results:

Patients with low opioid use (<5 mg oral morphine equivalent/d) survived longer than patients with high opioid (HO) use (≥5 mg oral morphine equivalent/d) (median overall survival of 315 vs. 150 d; hazard ratio [HR]=1.79; 95% confidence interval [CI]: 1.13, 2.84). This effect persisted on multivariate models (adjusted HR=2.76; 95% CI: 1.39, 5.48). Low opioid patients tended to respond better to treatment than HO patients, based on carbohydrate antigen 19-9. Patients with low MOP-R expression had longer median survival (230 vs. 193 d), though the HR was not significant (1.15; 95% CI: 0.71, 1.88). Baseline pain was not associated with outcomes.

Conclusion:

In patients with metastatic pancreatic adenocarcinoma, HO use is associated with decreased survival, but the severity of baseline pain and MOP-R expression score in tumor tissue does not correlate with clinical outcomes.
Comprehensive review of pelvic congestion syndrome: causes, symptoms, treatment options
Authors: Bendek Boleslaw , Afuape Nicole , Banks Elizabeth , Desai Nita A.
Published: June 2020

Purpose of review

The purpose of this publication is to review the currently available and most up-to-date information regarding the pathogenesis, diagnosis, and treatment of pelvic congestion syndrome.

Recent findings

The diagnosis of pelvic congestion syndrome is difficult to make; however, it should remain on the differential for chronic pelvic pain. The most recent available research seems to favour endovascular treatment with interventional radiology over surgical management, with high success rate and low occurrence of complications.

High-level evidence on the diagnosis and management of pelvic congestion syndrome is lacking. Only a small number of randomized controlled trials exist. More high-quality research is needed, particularly involving practicing obstetrician and gynecologists as the majority of these patients, and the clinical outcomes of any interventions implemented for pelvic congestion syndrome are ultimately managed by OB/GYN providers.
Daily Morning Blue Light Therapy Improves Daytime Sleepiness, Sleep Quality, and Quality of Life Following a Mild Traumatic Brain Injury
Authors: Raikes Adam C. , Dailey Natalie S. , Shane Bradley R. , Forbeck Brittany , Alkozei Anna , Killgore William D. S.
Published: June 2020

Objective:

Identify the treatment effects of 6 weeks of daily 30-minute sessions of morning blue light therapy compared with placebo amber light therapy in the treatment of sleep disruption following mild traumatic brain injury.

Design:

Placebo-controlled randomized trial.

Participants:

Adults aged 18 to 45 years with a mild traumatic brain injury within the past 18 months (n= 35).

Main Outcome Measures:

Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Beck Depression Inventory II, Rivermead Post-concussion Symptom Questionnaire, Functional Outcomes of Sleep Questionnaire, and actigraphy-derived sleep measures.

Results:

Following treatment, moderate to large improvements were observed with individuals in the blue light therapy group reporting lower Epworth Sleepiness Scale (Hedges'g= 0.882), Beck Depression Inventory II (g= 0.684), Rivermead Post-concussion Symptom Questionnaire chronic (g= 0.611), and somatic (g= 0.597) symptoms, and experiencing lower normalized wake after sleep onset (g= 0.667) than those in the amber light therapy group. In addition, individuals in the blue light therapy group experienced greater total sleep time (g= 0.529) and reported improved Functional Outcomes of Sleep Questionnaire scores (g= 0.929) than those in the amber light therapy group.

Conclusion:

Daytime sleepiness, fatigue, and sleep disruption are common following a mild traumatic brain injury. These findings further substantiate blue light therapy as a promising nonpharmacological approach to improve these sleep-related complaints with the added benefit of improved postconcussion symptoms and depression severity.
Mitochondrial dysfunction in critical illness during acute metabolic stress and convalescence: consequences for nutrition therapy
Authors: Moonen Hanneke Pierre Franciscus Xaverius , Van Zanten Arthur Raymond Hubert
Published: June 2020

Purpose of review

Mitochondrial dysfunction is associated with increased morbidity and mortality during and after critical illness. The concept of adaptive mitochondrial metabolic-bio-energetic downregulation rather than bio-energetic failure during the acute phase of critical illness has gained traction. As mitochondria are not able to utilize substrate during adaptive hibernation and aggressive feeding induces further harm, this condition has consequences for nutrition therapy.

Recent findings

Meeting resting energy expenditure in early critical illness is associated with enhanced oxidative stress and attenuation of autophagy, as is hyperglycemia. The negative effect of early high protein administration remains unclear, whereas fat appears bio-energetically inert. Although antioxidant micronutrients are essential to mitochondrial function, high-dosage studies of single vitamins (C and D) failed to show benefit. Convalescence probably requires increased micronutrient and macronutrient administration to aid anabolism and restore mitochondrial function, although robust data on requirements and actual intake are lacking.

Optimal nutrition therapy in the early phase of critical illness should avoid overfeeding and preserve (adaptive) mitochondrial function. Micronutrient supplementation probably requires a strategic cocktail instead of a high dosage of a single nutrient. Focus on identification of distinct metabolic phases to adapt nutrition during and after critical illness is essential.
Artificial intelligence in transplantation (machine-learning classifiers and transplant oncology)
Authors: Ivanics Tommy , Patel Madhukar S. , Erdman Lauren , Sapisochin Gonzalo
Published: June 2020

Purpose of review

To highlight recent efforts in the development and implementation of machine learning in transplant oncology – a field that uses liver transplantation for the treatment of hepatobiliary malignancies – and particularly in hepatocellular carcinoma, the most commonly treated diagnosis in transplant oncology.

Recent findings

The development of machine learning has occurred within three domains related to hepatocellular carcinoma: identification of key clinicopathological variables, genomics, and image processing.

Machine-learning classifiers can be effectively applied for more accurate clinical prediction and handling of data, such as genetics and imaging in transplant oncology. This has allowed for the identification of factors that most significantly influence recurrence and survival in disease, such as hepatocellular carcinoma, and thus help in prognosticating patients who may benefit from a liver transplant. Although progress has been made in using these methods to analyse clinicopathological information, genomic profiles, and image processed data (both histopathological and radiomic), future progress relies on integrating data across these domains.
Application of Suprafascially Harvested Anterolateral Thigh Perforator Flap for the Reconstruction of Oral and Maxillofacial Defects
Authors: Zhang Shanshan , Li Panchun , Liu Chang , Wu Hanjiang , Gong Zhaojian
Published: June 2020

Purpose:

The aim of this study was to evaluate the feasibility and efficacy of the suprafascially elevated anterolateral thigh (ALT) perforator flap for reconstructing oral and maxillofacial defects.

Patients and Methods:

The authors analyzed a retrospective case series of 15 patients who underwent reconstruction of oral and maxillofacial defects with the suprafascially raised ALT perforator flap from June 2015 through January 2017 at the Second Xiangya Hospital. The flap harvest and the methods for defect reconstruction are described, and the reconstructive efficacy is reported.

Results:

Of the 15 patients, 12 were men, and 3 were women, with an average age of 49.5 years. Postoperatively, all flaps survived completely, without vascular compromise or major wound complications. All patients were followed for approximately 1 to 37 months, and they were satisfied with the esthetic and functional results of the recipient- and donor- sites after the reconstruction.

Conclusions:

Because of the reduced donor-site complications, satisfactory esthetic and functional results, and high success rate of flap transplantation, the use of suprafascially harvested ALT perforator flap is a good choice for the reconstruction of oral and maxillofacial defects, in cases in which the fascia lata is not needed.
Cardiopexy at the Time of Sleeve Gastrectomy as a Preventive Measure for Reflux
Authors: Moon Rena C. , Teixeira Andre F. , Treto Jessica , Jawad Muhammad A.
Published: June 2020

Background:

One of the most significant concerns after laparoscopic sleeve gastrectomy (LSG) is the new-onset or worsening of gastroesophageal reflux disease (GERD). Some patients with LSG undergo a conversion to Roux-en-Y gastric bypass (RYGB) because of severe GERD. Cardiopexy at the time of LSG may help prevent GERD. This study aims to examine the safety and effectiveness of cardiopexy at the time of LSG.

Methods:

A retrospective chart review was performed on 161 consecutive patients who underwent LSG between May 1, 2017 and April 30, 2018. Of these, 79 underwent cardiopexy at the time of LSG. Weight, comorbidities, and complications were recorded at 6 months after LSG.

Results:

Baseline characteristics were similar between the cardiopexy and noncardiopexy groups of patients. In the cardiopexy group, 8 (10.1%) patients reported having GERD at the time of LSG, whereas 12 (14.6%) patients did in the noncardiopexy group. At 6 months after the procedure, 5 (8.9%) patients in the cardiopexy group reported symptoms of GERD, whereas 14 (17.7%) patients did in the noncardiopexy group (P=0.15). One (1.3%) patient in the cardiopexy group and 2 (2.4%) patients in the noncardiopexy group were converted to an RYGB because of severe reflux (P=0.58). The percentage of excess body mass index loss and the percentage of total weight loss were similar between the 2 groups.

Conclusion:

Cardiopexy was not associated with a reduced rate of symptomatic GERD and conversion to RYGB after 6 months.
COVID-19 Trend and Forecast in India: A Joinpoint Regression Analysis
Authors: Chaurasia Aalok Ranjan
Published: June 2020

This paper analyses the trend in daily reported confirmed cases of COVID-19 in India using joinpoint regression analysis. The analysis reveals that there has been little impact of the nation-wide lockdown and subsequent extension on the progress of the COVID-19 pandemic in the country and there is no empirical evidence to suggest that relaxations under the third and the fourth phase of the lockdown have resulted in a spike in the reported confirmed cases. The analysis also suggests that if the current trend continues, in the immediate future, then the daily reported confirmed cases of COVID-19 in the country is likely to increase to 21 thousand by 15 June 2020 whereas the total number of confirmed cases of COVID-19 will increase to around 422 thousand. The analysis calls for a population-wide testing approach to check the increase in the reported confirmed cases of COVID-19.
The Aging Slow Wave: A Shifting Amalgam of Distinct Slow Wave and Spindle Coupling Subtypes Define Slow Wave Sleep Across the Human Lifespan
Authors: McConnell Brice V. , Kronberg Eugene , Teale Peter D. , Fishback Grace M. , Kaplan Rini I. , Sillau Stefan H. , Fought Angela J. , Dhanasekaran A. Ranjitha , Berman Brian D. , Ramos Alberto R. , McClure Rachel L. , Bettcher Brianne M.
Published: June 2020

Study Objectives

Slow wave and spindle coupling supports memory consolidation, and loss of coupling is linked with cognitive decline and neurodegeneration. Coupling is proposed to be a possible biomarker of neurological disease, yet little is known about the different subtypes of coupling that normally occur throughout human development and aging. Here we identify distinct subtypes of spindles within slow wave upstates and describe their relationships with sleep stage across the human lifespan.

Methods

Coupling within a cross-sectional cohort of 582 subjects was quantified from stages N2 and N3 sleep across ages 6-88 years old. Results were analyzed across the study population via mixed model regression. Within a subset of subjects, we further utilized coupling to identify discrete subtypes of slow waves by their coupled spindles.

Results

Two different subtypes of spindles were identified during the upstates of (distinct) slow waves: an “early-fast” spindle, more common in stage N2 sleep, and a “late-fast” spindle, more common in stage N3. We further found stages N2 and N3 sleep are composed of two discrete subtypes of slow waves, each identified by their unique coupled-spindle timing and frequency. The relative contribution of coupling subtypes shifts across the human lifespan, and a deeper sleep phenotype prevails during old age.

Conclusions

Distinct subtypes of slow waves and coupled spindles form the composite of slow wave sleep. Our findings support a model of sleep-dependent synaptic regulation via discrete slow wave/spindle coupling subtypes and advance a conceptual framework for the development of coupling-based biomarkers in age-associated neurological disease.

Statement of Significance

Slow waves of nonrapid eye movement sleep couple with sleep spindles in a process hypothesized to support memory functions. This coupling has recently gained interest as a possible biomarker of cognitive aging and onset of Alzheimer’s disease. Most studies have been limited by an assumption that all slow waves (and coupled spindles) are fundamentally the same physiological events. Here we demonstrate that distinct subtypes of slow waves and their coupled spindles can be identified in human sleep. A mixture of different slow wave and spindle subtypes shifts in composition during lighter versus deeper sleep, and aging favors the deep sleep subtypes. These data should inform any future attempts to use slow wave sleep as a biomarker or clinical interventional target.
Evaluating the impact of demographic, socioeconomic factors, and risk aversion on mobility during COVID-19 epidemic in France under lockdown: a population-based study
Authors: Pullano Giulia , Valdano Eugenio , Scarpa Nicola , Rubrichi Stefania , Colizza Vittoria
Published: June 2020

On March 17, 2020, French authorities implemented a nationwide lockdown to respond to COVID-19 epidemic and curb the surge of patients requiring critical care, similarly to other countries. Evaluating the impact of lockdown on population mobility is essential to quantify achievable reductions and identify the factors driving the changes in social dynamics that affected viral diffusion. We used temporally resolved travel flows among 1,436 administrative areas of mainland France reconstructed from mobile phone trajectories. We measured mobility changes before and during lockdown at both local and country scales. Lockdown caused a 65% reduction in countrywide number of displacements, and was particularly effective in reducing work-related short-range mobility, especially during rush hours, and recreational trips. Geographical heterogeneities showed anomalous increases in long-range movements even before lockdown announcement that were tightly localized in space. During lockdown, mobility drops were unevenly distributed across regions. They were strongly associated with active population, workers employed in sectors highly impacted by lockdown, and number of hospitalizations per region, and moderately associated with socio-economic level of the region. Major cities largely shrank their pattern of connectivity, reducing it mainly to short-range commuting. Lockdown was effective in reducing population mobility across scales. Caution should be taken in the timing of policy announcements and implementation, as anomalous mobility followed policy announcements that may act as seeding events. On the other hand, risk aversion may be beneficial in further decreasing mobility in largely affected regions. Socio-economic and demographic constraints to the efficacy of restrictions were also identified. The unveiled links between geography, demography, and timing of the response to mobility restrictions may help design interventions that minimize invasiveness while contributing to the current epidemic response.

Funding

ANR projects EVALCOVID-19 (ANR-20-COVI-0007) and DATAREDUX (ANR-19-CE46-0008-03); EU H2020 grants RECOVER (H2020-101003589) and MOOD (H2020-874850); REACTing COVID-19 modeling grant.
Determinants of self-reported symptoms and testing for COVID in Canada using a nationally representative survey
Authors: Wu Daphne C , Jha Prabhat , Lam Teresa , Brown Patrick , Gelband Hellen , Nagelkerke Nico , Birnboim H. Chaim , Reid Angus
Published: June 2020

In April 2020, the first-ever nationally representative survey in Canada polled 4,240 adults age 18 years and older about their COVID experience in March, early in the epidemic. We examined determinants of COVID symptoms, defined as fever plus difficulty breathing/shortness of breath, dry cough so severe that it disrupts sleep, and/or loss of sense of smell; and testing for SARS-CoV-2 by respondents and/or household members. About 8% of Canadians reported that they and/or one or more household members experienced COVID symptoms. Symptoms were more common in younger than older adults, and among visible minorities. Overall, only 3% of respondents and/or household members reported testing for SARS-CoV-2. Being tested was associated with having COVID symptoms, Indigenous identity, and living in Quebec. Periodic nationally representative surveys—including high-risk older populations—of symptoms, as well as SARS-CoV-2 antibodies, are required in many countries to understand the pandemic and prepare for the future.
Perceptual gating of a brainstem reflex facilitates speech understanding in human listeners
Authors: Hernandez-Perez Heivet , Mikiel-Hunter Jason , McAlpine David , Dhar Sumitrajit , Boothalingam Sriram , Monaghan Jessica J.M. , McMahon Catherine M.
Published: June 2020

Navigating “cocktail party” situations by enhancing foreground sounds over irrelevant background information is typically considered from a cortico-centric perspective. However, subcortical circuits, such as the medial olivocochlear (MOC) reflex that modulates inner ear activity itself, have ample opportunity to extract salient features from the auditory scene prior to any cortical processing. To understand the contribution of auditory subcortical nuclei and the cochlea, physiological recordings were made along the auditory pathway while listeners differentiated non(sense)-words and words. Both naturally-spoken and intrinsically-noisy, vocoded speech — filtering that mimics processing by a cochlear implant—significantly activated the MOC reflex, whereas listening to speech-in-background noise revealed instead engagement of midbrain and cortical resources. An auditory periphery model reproduced these speech degradation-specific effects, providing a rationale for goal-directed gating of the MOC reflex to enhance representation of speech features in the auditory nerve. Our data reveals the co-existence of two strategies in the auditory system that may facilitate speech understanding in situations where the speech signal is either intrinsically degraded or masked by extrinsic auditory information.