bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusual complication of colonic carcinoma: colonopleurobronchial fistula
Authors: Sherwani Poonam , Rakesh Nirjhar Raj , Kumar Sumit , Saxena Sudhir
Published: December 2020

Colonopleurobronchial fistula (CPBF) is a rare complication which occurs due to diversified causes. Expectoration of the faecal material is the classical clinical symptom which suggests the diagnosis. Various causes include infection of pulmonary or abdominal origin, inflammatory bowel disease, colonic malignancy, diaphragmatic hernia and colonic interposition. Crohn’s disease is the frequent underlying pathology, colonic malignancy accounts for rare cause. Due to the presence of liver in right upper quadrant, most of the fistulas are on the left side. Here we describe a rare case of a 38-year-old man presented with right-sided CPBF due to underlying colonic malignancy. Bronchial block was done, however the patient succumbed to death.
Atypical hereditary spherocytosis phenotype associated with pseudohypokalaemia and a new variant in the band 3 protein
Authors: Ramasamy Indra
Published: December 2020

Red blood cell (RBC) membrane disorders are predominantly caused by mutations resulting in decreased RBC deformability and permeability. We present a family in which, the proband and his daughter presented with pseudohypokalaemia. Studies on the temperature dependence of pseudohypokalaemia suggested a maximum decrease in serum potassium when whole blood is stored at 37°C. Routine haematology suggested mild haemolysis with a hereditary spherocytosis phenotype. These two cases present a novel variant in temperature-dependent changes in potassium transport. A new variant was identified in the SLC4A1 gene which codes for band 3 protein (anion exchanger 1) in RBC membrane which may contribute to the phenotype. This is the first report of familial pseudohypokalaemia associated with changes in RBC membrane morphology. The clinical implications of pseudohypokalaemia are that it can lead to inappropriate investigation or treatment. However, many questions remain to be solved and other RBC membrane protein genes should be studied.
Non-infective supraglottitis: two cases of unusual aetiology
Authors: Kenyon Olivia , Blackabey Victoria , Talwar Rishi
Published: December 2020

Supraglottitis is an ear, nose and throat emergency where swelling of the laryngeal structures can threaten to fatally obstruct the airway. Most cases of supraglottitis are of infective origin but other rarer causes have been documented. We present two patients who presented with stridor and were found to have supraglottic oedema on fibreoptic nasolaryngoscopy. Both patients presented with odynophagia and progressive dyspnoea and were initially medically managed to stabilise their airway. This included intravenous steroids, nebulised epinephrine and intravenous antibiotics. After this initial treatment they both required investigation and optimisation of their underlying medical conditions (rheumatoid arthritis with possible systemic lupus erythematosus and nephrotic syndrome) as more definitive management.
Prevalence and correlates of depression among black and Latino stroke survivors with uncontrolled hypertension: a cross-sectional study
Authors: Ogunlade Adebayo O , Williams Stephen K , Joseph Jennifer , Onakomaiya Deborah O , Eimicke Joseph P , Teresi Jeanne A , Williams Olajide , Ogedegbe Gbenga , Spruill Tanya M
Published: December 2020

Objective

To examine the prevalence and correlates of depression in a cohort of black and Hispanic stroke survivors with uncontrolled hypertension.

Setting

Baseline survey data from 10 stroke centres across New York City.

Participants

Black and Hispanic stroke survivors with uncontrolled hypertension (n=450).

Outcome measures

Depressive symptoms were assessed with the 8-item Patient Reported Outcomes Measurement Information System (PROMIS) measure. Depression was defined as a PROMIS score ≥55. Other data collected included clinical factors, health-related quality of life (EuroQoL five dimensions (EQ-5D)), functional independence (Barthel Index, BI), stroke-related disability (Modified Rankin Score), physical function (PROMIS Physical Function) and executive functioning (Frontal Assessment Battery).

Results

The mean age was 61.7±11.1 years, 44% of participants were women and 51% were black. Poststroke depression was noted in 32% of the cohort. Examining bivariate relationships, patients with depression were observed to have poorer function and quality of life as evidenced by significantly lower PROMIS physical function scores (36.9±8.32 vs 43.4±10.19, p<0.001); BI scores (79.9±19.2 vs 88.1±15.1, p<0.001); EQ-5D scores (0.66±0.24 vs 0.83±0.17, p<0.001) and higher Rankin scores (2.10±1.00 vs 1.46±1.01, p<0.001) compared with those without depression. Multivariate (model adjusted) significant correlates of depression included lower self-reported quality of life (OR=0.02 (CI 0.004 to 0.12) being younger (OR=0.94; 95% CI 0.91 to 0.97); not married (OR=0.46; CI 0.24 to 0.89)); and foreign-born (OR=3.34, 95% CI 1.4 to 7.97). There was a trend for higher comorbidity to be uniquely associated with depression (≥3 comorbid conditions, OR=1.49, 95% CI 1.00 to 2.23).

Conclusions

Poststroke depression is common among black and Hispanic stroke survivors with higher rates noted among foreign-born patients and those with high comorbidity. These findings highlight the importance of screening for depression in minority stroke survivors.

Trial registration number

http://www.clinicaltrials.gov. Unique identifier: NCT01070056.
Informant-based assessment instruments for dementia and their measurement properties in persons with intellectual disability: systematic review protocol
Authors: Zeilinger Elisabeth L , Komenda Sophie , Zrnic Irina , Franken Fabian , Woditschka Katharina
Published: December 2020

Introduction

Persons with intellectual disability (ID) are at a higher risk of developing dementia than persons without ID, with an expected earlier onset. Assessment methods for the general population cannot be applied for persons with ID due to their pre-existing intellectual and functional impairments. As there is no agreed-upon measure to assess dementia in persons with ID, multiple instruments for this purpose have been developed and adapted in the past decades. This review aimed to identify all available informant-based instruments for the assessment of dementia in persons with ID, to evaluate and compare them according to their measurement properties, and to provide a recommendation for the most suitable instruments. Additionally, an overview of the amount and quality of research on these instruments will be provided.

Methods and analysis

This review will be conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We will adhere to the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines and use a set of characteristics developed for assessment instruments for persons with ID, the Characteristics of Assessment Instruments for Psychiatric Disorders in Persons with Intellectual Developmental Disorders. Two comprehensive, systematic literature searches will be applied in 10 international databases, including ASSIA, CINAHL, Cochrane Library, ERIC, MEDLINE, PsycINFO, Scopus, Web of Science, OpenGrey and ProQuest Dissertations and Theses Global. Risk of bias and quality assessment will be done according to COSMIN guidelines. We will apply the modified Grading of Recommendations, Assessment, Development and Evaluation approach to rate the overall quality of the available evidence.

Ethics and dissemination

No ethics statement is needed for this study. The results will be submitted to a peer-reviewed journal and will be presented at international conferences.
Protocol for a systematic review and meta-analysis of respiratory rehabilitation following intensive care unit discharge for COVID-19 survivors
Authors: Wang Dan , Li Jin , Zhu Feilong , Hong Qianqin , Zhang Ming , Gao Min , Chen Wei
Published: December 2020

Introduction

Both physical and mental disorders may be exacerbated in patients with COVID-19 due to the experience of receiving intensive care; undergoing prolonged mechanical ventilation, sedation, proning and paralysis. Pulmonary rehabilitation is aimed to improve dyspnoea, relieve anxiety and depression, reduce the incidence of related complications, as well as prevent and improve dysfunction. However, the impact of respiratory rehabilitation on discharged patients with COVID-19 is currently unclear, especially on patients who have been mechanically ventilated over 24 hours. Therefore, we aim to investigate the efficacy of respiratory rehabilitation programmes, initiated after discharge from the intensive care unit, on the physical and mental health and health-related quality of life in critical patients with COVID-19.

Methods and analysis

We have registered the protocol on PROSPERO and in the process of drafting it, we strictly followed the checklist of Preferred Reporting Items for Systematic Review and Meta-Analysis Potocols. We will search the PubMed, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, WanFang, VIP information databases and Chinese Biomedical Literature Database. Additionally, ongoing trials in the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov and ISRCTN registry will be searched as well. Studies in English or Chinese and from any country will be accepted regardless of study design. Two review authors will independently extract data and assess the quality of included studies. Continuous data are described as standard mean differences (SMDs) with 95% CIs. Dichotomous data from randomised controlled trials are described as risk ratio(RR) with 95% CIs; otherwise, it is described as odds ratio(OR) with 95% CIs. I2 and the Cochrane’s Q statistic will be used to conduct heterogeneity assessment. The quality of evidence of main outcomes will be evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation(GRADE) criteria. When included studies are sufficient, we will conduct subgroup analysis and sensitivity analysis; the publication bias will be statistically analysed using a funnel plot analysis and Egger’s test.

Ethics and dissemination

Our review, planning to include published studies, does not need the request to the ethical committee. The final results of this review will be published in a peer-reviewed journal after completion.

Patient and public involvement

No patient involved.

PROSPERO registration number

CRD42020186791.
Factors affecting the use of neurally adjusted ventilatory assist in the adult critical care unit: a clinician survey
Authors: Hadfield Daniel , Rose Louise , Reid Fiona , Cornelius Victoria , Hart Nicholas , Finney Clare , Penhaligon Bethany , Harris Clare , Saha Sian , Noble Harriet , Smith John , Hopkins Philip Anthony , Rafferty Gerrard Francis
Published: December 2020

Background

Neurally adjusted ventilatory assist (NAVA) involves an intricate interaction between patient, clinician and technology. To improve our understanding of this complex intervention and to inform future trials, this survey aimed to examine clinician attitudes, beliefs and barriers to NAVA use in critically ill adults within an institution with significant NAVA experience.

Methods

A survey of nurses, doctors and physiotherapists in four Intensive Care Units (ICUs) of one UK university-affiliated hospital (75 NAVA equipped beds). The survey consisted of 39 mixed open and structured questions. The hospital had 8 years of NAVA experience prior to the survey.

Results

Of 466 distributed questionnaires, 301 (64.6%) were returned from 236 nurses (78.4%), 53 doctors (17.6%) and 12 physiotherapists (4.0%). Overall, 207/294 (70.4%) reported clinical experience. Most agreed that NAVA was safe (136/177, 76.8%) and clinically effective (99/176, 56.3%) and most perceived ‘improved synchrony’, ‘improved comfort’ and ‘monitoring the diaphragm’ to be key advantages of NAVA. ‘Technical issues’ (129/189, 68.3%) and ‘NAVA signal problems’ (94/180, 52.2%) were the most cited clinical disadvantage and cause of mode cross-over to Pressure Support Ventilation (PSV), respectively. Most perceived NAVA to be more difficult to use than PSV (105/174, 60.3%), although results were mixed when compared across different tasks. More participants preferred PSV to NAVA for initiating ventilator weaning (93/171 (54.4%) vs 29/171 (17.0%)). A key barrier to use and a consistent theme throughout was ‘low confidence’ in relation to NAVA use.

Conclusions

In addition to broad clinician support for NAVA, this survey describes technical concerns, low confidence and a perception of difficulty above that associated with PSV. In this context, high-quality training and usage algorithms are critically important to the design and of future trials, to clinician acceptance and to the clinical implementation and future success of NAVA.
Quantifying asymmetry of anterior cerebral arteries as a predictor of anterior communicating artery complex aneurysm
Authors: Burlakoti Arjun , Kumaratilake Jaliya , Taylor David J , Henneberg Maciej
Published: December 2020

Objectives

The aim of this study was to establish an anatomical index for early prediction of the risk of development of aneurysms in anterior communicating arterial complex (AcomAC). The asymmetric diameter of one anterior cerebral artery (ACA) to other could alter haemodynamics and may contribute to formation of aneurysms in AcomAC and be a reliable predictor of the risk of development of aneurysms.

Design and setting

This is a retrospective, observational and quantitative study, which used cerebral computed tomography angiography (CCTA) scans in South Australia.

Participants

CCTA scans of 166 adult patients of both sexes were studied.

Main outcome measures

The internal diameters of the proximal segments of ACAs (A1s) were measured. Position and presence or absence of aneurysms in AcomAC were determined. The ratio of A1 diameters was taken as a measure of A1 asymmetry.

Results

The ratio of diameters of A1s correlated with the occurrence of AcomAC aneurysms. The risk of development of aneurysms in AcomAC was much greater (80%, OR=47.3) when one A1 segment’s radius was at least 50% larger (ie, 2.25 times cross-sectional area) than the other.

Conclusion

The general information on asymmetric A1 has been published previously. The present findings have significant contribution since the A1s asymmetry ratios have been categorised in ascending order and matched with the presence of AcomAC aneurysms. The asymmetry ratio of the A1 is a good predictor for the development of AcomAC aneurysms. Reconstruction of the asymmetric A1 could be done if the technology gets advanced.
Apnoeic oxygenation was associated with decreased desaturation rates during rapid sequence intubation in multiple Australian and New Zealand emergency departments
Authors: Perera Adrian , Alkhouri Hatem , Fogg Toby , Vassiliadis John , Mackenzie John , Wimalasena Yashvi
Published: December 2020

Apnoeic oxygenation (ApOx) has been demonstrated to reduce the incidence of desaturation, although evidence of benefit has been conflicting depending on the technique used. The aim of this study was to compare the incidence of desaturation between patients who received ApOx via conventional nasal cannula (NC) and those who did not, using a large, multicentre airway registry.

Methods

This study is an analysis of 24 months of prospectively collected data in the Australia and New Zealand Emergency Department Airway Registry (June 2013–June 2015). The registry includes information on all intubated adults from 43 emergency departments. Patients intubated during cardiac arrest (n=393), those who received active ventilation prior to the first intubation attempt (n=486), and where the use of ApOx was not recorded either way (n=312) were excluded. The proportion of patients who desaturated (Sa02<93) in the group that received ApOx and those that did not were compared. To evaluate the association of ApOx with patient desaturation, a logistic regression model based on factors expected to influence desaturation was performed.

Results

Of 2519 patients analysed, 1669 (66.3%) received ApOx via NC while 850 (33.7%) did not. Desaturation in the cohort receiving ApOx was 10.4% compared with standard care (no ApOx) 13.7%. ApOx had a protective effect for desaturation (OR 0.71 95% CI 0.53 to 0.95). Single intubation attempt was associated with reduced risk of desaturation of (OR 0.10, 95% CI 0.06 to 0.17); this was increased on second attempt (OR 0.37, 95% CI 0.21 to 0.68). Desaturation was also associated with the physician recording that they had anticipated a difficult airway (OR 1.83, 95% CI 1.34 to 2.48).

Conclusion

This large multicentre registry study provides evidence that ApOx delivered through a conventional NC is associated with a lower incidence of desaturation in patients undergoing rapid sequence intubation.

Trial registration number

ACTRN12613001052729.
Physical health conditions and subsequent union separation: a couple-level register study on neurological conditions, heart and lung disease, and cancer
Authors: Metsä-Simola Niina , Einiö Elina , Peltonen Riina , Martikainen Pekka
Published: December 2020

Background

Studies that assess the role of physical health conditions on separation risk are scarce and mostly lack health information on both partners. It is unclear how the association between physical illness and separation risk varies by type of illness, gender of the ill spouse and age of the couple.

Methods

We used Finnish register data on 127 313 couples to examine how neurological conditions, heart and lung disease, and cancer are associated with separation risk. The data included information on medication, hospitalisations, separations and sociodemographic characteristics. Marital and non-marital cohabiting couples aged 40–70 years were followed from 1998 to 2003 for the onset of health conditions and subsequent separation, and Cox regression was used to examine the associations.

Results

Compared with healthy couples, the HR of separation was elevated by 43% for couples in which both spouses had a physical health condition, by 22% for couples in which only the male spouse had fallen ill, and by 11% for couples in which only the female had fallen ill. Among older couples, the associations between physical illness and separation risk were even clearer. The association with separation risk was strongest for neurological conditions, and after incidence of these conditions among males, separation risk increased over time. Adjustment for sociodemographic characteristics had little effect.

Conclusions

Our findings suggest that poor health may largely strain relationships through disability and associated burden of spousal care, and this should be taken into consideration when planning support services for couples with physical health conditions.
A20 regulates the therapeutic effect of anti-PD-1 immunotherapy in melanoma
Authors: Guo Weinan , Ma Jinyuan , Guo Sen , Wang Huina , Wang Sijia , Shi Qiong , Liu Lin , Zhao Tao , Yang Fengfan , Chen Shuyang , Chen Jianru , Zhao Jianhong , Yu Chen , Yi Xiuli , Yang Yuqi , Ma Jingjing , Ni Qingrong , Zhu Guannan , Gao Tianwen , Li Chunying
Published: December 2020

Background

The therapeutic effect of immune checkpoint blockers, especially the neutralizing antibodies of programmed cell death (PD-1) and its ligand programmed death ligand 1 (PD-L1), has been well verified in melanoma. Nevertheless, the dissatisfactory response rate and the occurrence of resistance significantly hinder the treatment effect. Inflammation-related molecules like A20 are greatly implicated in cancer immune response, but the role of tumorous A20 in antitumor immunity and immunotherapy efficacy remains elusive.

Methods

The association between tumorous A20 expression and the effect of anti-PD-1 immunotherapy was determined by immunoblotting, immunofluorescence staining and flow cytometry analysis of primary tumor specimens from melanoma patients. Preclinical mouse model, in vitro coculture system, immunohistochemical staining and flow cytometry analysis were employed to investigate the role of A20 in regulating the effect of anti-PD-1 immunotherapy. Bioinformatics, mass spectrum analysis and a set of biochemical analyzes were used to figure out the underlying mechanism.

Results

We first discovered that upregulated A20 was associated with impaired antitumor capacity of CD8+T cells and poor response to anti-PD-1 immunotherapy in melanoma patients. Subsequent functional studies in preclinical mouse model and in vitro coculture system proved that targeting tumorous A20 prominently improved the effect of immunotherapy through the invigoration of infiltrating CD8+T cells via the regulation of PD-L1. Mechanistically, A20 facilitated the ubiquitination and degradation of prohibitin to potentiate STAT3 activation and PD-L1 expression. Moreover, tumorous A20 expression was highly associated with the ratio of Ki-67 percentage in circulating PD-1+CD8+T cells to tumor burden.

Conclusions

Together, our findings uncover a novel crosstalk between inflammatory molecules and antitumor immunity in melanoma, and highlight that A20 can be exploited as a promising target to bring clinical benefit to melanomas refractory to immune checkpoint blockade.
Five-year results of randomized bioactive versus bare metal coils in the treatment of intracranial aneurysms: the Matrix and Platinum Science (MAPS) Trial
Authors: McDougall Cameron G , Johnston S Claiborne , Hetts Steven W , Gholkar Anil , Barnwell Stanley L , Vazquez Suarez Juan Carlos , Massó Romero Javier , Chaloupka John C , Bonafe Alain , Wakhloo Ajay K , Tampieri Donatella , Dowd Christopher F , Fox Allan J , Turk Aquilla S
Published: December 2020

Background

No randomized trial of intracranial aneurysm coiling has compared long-term efficacy of polymer-modified coils to bare metal coils (BMCs). We report 5-year results comparing Matrix2coils to BMCs. The primary objective was to compare the rates of target aneurysm recurrence (TAR) at 12 months. Secondary objectives included angiographic outcomes at TAR or 12 months and TAR at 5 years.

Methods

A total of 626 patients were randomized to BMCs or Matrix2coils. Detailed methods and 1-year results have been published previously.

Results

Of 580 patients eligible for 5-year follow-up, 431 (74.3%) completed follow-up or reached TAR. Matrix2coils were non-inferior to BMCs (P=0.8) but did not confer any benefit. Core lab reported post-treatment residual aneurysm filling (Raymond III) correlated with TAR (P<0.0001) and with aneurysm hemorrhage after treatment (P<0.008). Repeat aneurysmal hemorrhage after treatment, but before hospital discharge, occurred in three patients treated for acutely ruptured aneurysms. Additionally, two patients treated for unruptured aneurysms experienced a first hemorrhage during follow-up. All five hemorrhages resulted from aneurysms with Raymond III residual aneurysm filling persisting after initial treatment. After 5 years follow-up, 2/626 (0.3%) patients are known to have had target aneurysm rupture following hospital discharge. The annualized rate of delayed hemorrhage after coiling was 2/398/5=0.001 (0.1%) per year for unruptured aneurysms and 0 for ruptured aneurysms.

Conclusions

After 5 years Matrix2coils were non-inferior to BMCs but no benefit was demonstrated. Post-treatment residual angiographic aneurysm filling (Raymond III) is strongly associated with TAR (P<0.0001) and post-treatment aneurysmal hemorrhage (P=0.008).
Per-pass analysis of acute ischemic stroke clots: impact of stroke etiology on extracted clot area and histological composition
Authors: Fitzgerald Seán , Rossi Rosanna , Mereuta Oana Madalina , Jabrah Duaa , Okolo Adaobi , Douglas Andrew , Molina Gil Sara , Pandit Abhay , McCarthy Ray , Gilvarry Michael , Dunker Dennis , Nordanstig Annika , Ceder Erik , Redfors Petra , Jood Katarina , Dehlfors Niclas , Magoufis Georgios , Tsivgoulis Georgios , Brinjikji Waleed , Kallmes David F , O'Hare Alan , Power Sarah , Brennan Paul , Alderson Jack , Nagy András , Vadász Ágnes , Psychogios Klearchos , Szikora Istvan , Tatlisumak Turgut , Rentzos Alexandros , Thornton John , Doyle Karen M
Published: December 2020

Background

Initial studies investigating correlations between stroke etiology and clot composition are conflicting and do not account for clot size as determined by area. Radiological studies have shown that cardioembolic strokes are associated with shorter clot lengths and lower clot burden than non-cardioembolic clots.

Objective

To report the relationship between stroke etiology, extracted clot area, and histological composition at each procedural pass.

Methods

As part of the multi-institutional RESTORE Registry, the Martius Scarlett Blue stained histological composition and extracted clot area of 612 per-pass clots retrieved from 441 patients during mechanical thrombectomy procedures were quantified. Correlations with clinical and procedural details were investigated.

Results

Clot composition varied significantly with procedural passes; clots retrieved in earlier passes had higher red blood cell content (H4=11.644, p=0.020) and larger extracted clot area (H4=10.730, p=0.030). Later passes were associated with significantly higher fibrin (H4=12.935, p=0.012) and platelets/other (H4=15.977, p=0.003) content and smaller extracted clot area. Large artery atherosclerotic (LAA) clots were significantly larger in the extracted clot area and more red blood cell-rich than other etiologies in passes 1–3. Cardioembolic and cryptogenic clots had similar histological composition and extracted clot area across all procedural passes.

Conclusion

LAA clots are larger and associated with a large red blood cell-rich extracted clot area, suggesting soft thrombus material. Cardioembolic clots are smaller in the extracted clot area, consistent in composition and area across passes, and have higher fibrin and platelets/other content than LAA clots, making them stiffer clots. The per-pass histological composition and extracted clot area of cryptogenic clots are similar to those of cardioembolic clots, suggesting similar formation mechanisms.
Optimising development and production of naturally fractured reservoirs using a large empirical dataset
Authors: Sun Shaoqing , Pollitt David A.
Published: December 2020

Naturally fractured reservoirs are important contributors to global petroleum reserves and production. Existing classification schemes for fractured reservoirs do not adequately differentiate between certain types of fractured reservoirs, leading to difficulty in understanding fundamental controls on reservoir performance and recovery efficiency. Three hundred naturally fractured reservoirs were examined to define a new classification scheme that is independent of the type of fracturing and describes fundamentally different matrix types, rock properties, fluid storage and flow characteristics.

This study categorises fractured reservoirs in three groups: (1) Type 1: characterized by a tight matrix where fractures and solution-enhanced fracture porosity provide both storage capacity and fluid-flow pathways; (2) Type 2: characterized by a macroporous matrix which provides the primary storage capacity where fractures and solution-enhanced fracture porosity provide essential fluid-flow pathways; and (3) Type 3: characterized by a microporous matrix which provides all storage capacity where fractures only provide essential fluid-flow pathways. Differentiation is made between controls imparted by inherent natural conditions, such as rock and fluid properties and natural drive mechanisms, and human controls, such as choice of development scheme and reservoir management practices.

The classification scheme presented here is based on reservoir and production characteristics of naturally fractured reservoirs and represents a refinement of existing schemes. This refinement allows accurate comparisons to be made between analogous fractured reservoirs, and trends and outliers in reservoir performance to be identified. Case histories provided herein demonstrate the practical application of this new classification scheme and the benefits that arise when applying it to the understanding of naturally fractured reservoirs.
Challenges of carbonate platform identification and characterization from seismic data in frontier exploration – evaluating a possible Miocene example from the SE Caribbean
Authors: Jiménez Berrocoso Álvaro , Masini Massimiliano , Salazar Josgre , Campos Antonio Olaiz , Hsieh Jean C. C.
Published: December 2020

The purpose of this study is to demonstrate that the identification of carbonate platforms in frontier exploration using seismic data remains challenging despite the variety of attributes that can be extracted from the data and their integration with other sources of information. A Miocene example from offshore Tobago (Southern Caribbean) is evaluated using 3D seismic data integrated with regional geology, potential fields, analogues and structural restoration. The data are compatible with interpreting the target as shallow-marine carbonates, and a conceptual model is presented. However, far fewer of the seismic characteristics are
diagnostic
of a carbonate platform, and despite the intensive approach and the use of published criteria for subsurface carbonate interpretation, it was impossible to conclusively identify the target as a shallow-marine carbonate. Alternative explanations such as volcaniclastics, eroded remnants of siliciclastics and basement highs are considered. The study illustrates that it is common to find situations where the origin of a prospective geobody cannot be determined beyond significant levels of uncertainty unless it is drilled. If other elements of the petroleum system are favourable, this irreducible risk has to be accepted to avoid overlooking attractive carbonate reservoirs, provided all available data are used and all possible alternative interpretations considered.
Increased cholinergic activity under conditions of low estrogen leads to adverse cardiac remodeling
Authors: Teixeira Vanessa P. , Miranda Kiany , Scalzo Sergio , Rocha-Resende Cibele , Silva Mário Morais , Tezini Geisa C. S. V. , Melo Marcos B. , Souza-Neto Fernando Pedro , Silva Kaoma S. C. , Jesus Itamar C. G. , Santos Anderson K. , de Oliveira Mauro , Szawka Raphael E. , Salgado Helio C. , Prado Marco Antonio Máximo , Poletini Maristela O. , Guatimosim Silvia
Published: December 2020

Cholinesterase inhibitors are used in postmenopausal women for the treatment of neurodegenerative diseases. Despite their widespread use in the clinical practice, little is known about the impact of augmented cholinergic signaling on cardiac function under reduced estrogen conditions. To address this gap, we subjected a genetically engineered murine model of systemic vesicular acetylcholine transporter overexpression ( Chat-ChR2) to ovariectomy and evaluated cardiac parameters. Left-ventricular function was similar between Chat-ChR2 and wild-type (WT) mice. Following ovariectomy, WT mice showed signs of cardiac hypertrophy. Conversely, ovariectomized (OVX) Chat-ChR2 mice evolved to cardiac dilation and failure. Transcript levels for cardiac stress markers atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were similarly upregulated in WT/OVX and Chat-ChR2/OVX mice. 17β-Estradiol (E2) treatment normalized cardiac parameters in Chat-ChR2/OVX to the Chat-ChR2/SHAM levels, providing a link between E2 status and the aggravated cardiac response in this model. To investigate the cellular basis underlying the cardiac alterations, ventricular myocytes were isolated and their cellular area and contractility were assessed. Myocytes from WT/OVX mice were wider than WT/SHAM, an indicative of concentric hypertrophy, but their fractional shortening was similar. Conversely, Chat-ChR2/OVX myocytes were elongated and presented contractile dysfunction. E2 treatment again prevented the structural and functional changes in Chat-ChR2/OVX myocytes. We conclude that hypercholinergic mice under reduced estrogen conditions do not develop concentric hypertrophy, a critical compensatory adaptation, evolving toward cardiac dilation and failure. This study emphasizes the importance of understanding the consequences of cholinesterase inhibition, used clinically to treat dementia, for cardiac function in postmenopausal women.
Molecular nature and physiological role of the mitochondrial calcium uniporter channel
Authors: Alevriadou B. Rita , Patel Akshar , Noble Megan , Ghosh Sagnika , Gohil Vishal M. , Stathopulos Peter B. , Madesh Muniswamy
Published: December 2020

Calcium (Ca2+) signaling is critical for cell function and cell survival. Mitochondria play a major role in regulating the intracellular Ca2+ concentration ([Ca2+]i). Mitochondrial Ca2+ uptake is an important determinant of cell fate and governs respiration, mitophagy/autophagy, and the mitochondrial pathway of apoptosis. Mitochondrial Ca2+ uptake occurs via the mitochondrial Ca2+ uniporter (MCU) complex. This review summarizes the present knowledge on the function of MCU complex, regulation of MCU channel, and the role of MCU in Ca2+ homeostasis and human disease pathogenesis. The channel core consists of four MCU subunits and essential MCU regulators (EMRE). Regulatory proteins that interact with them include mitochondrial Ca2+ uptake 1/2 (MICU1/2), MCU dominant-negative β-subunit (MCUb), MCU regulator 1 (MCUR1), and solute carrier 25A23 (SLC25A23). In addition to these proteins, cardiolipin, a mitochondrial membrane-specific phospholipid, has been shown to interact with the channel core. The dynamic interplay between the core and regulatory proteins modulates MCU channel activity after sensing local changes in [Ca2+]i, reactive oxygen species, and other environmental factors. Here, we highlight the structural details of the human MCU heteromeric assemblies and their known roles in regulating mitochondrial Ca2+ homeostasis. MCU dysfunction has been shown to alter mitochondrial Ca2+ dynamics, in turn eliciting cell apoptosis. Changes in mitochondrial Ca2+ uptake have been implicated in pathological conditions affecting multiple organs, including the heart, skeletal muscle, and brain. However, our structural and functional knowledge of this vital protein complex remains incomplete, and understanding the precise role for MCU-mediated mitochondrial Ca2+ signaling in disease requires further research efforts.
Inflammasome activation in acute lung injury
Authors: McVey Mark J. , Steinberg Benjamin E. , Goldenberg Neil M.
Published: December 2020

Inflammasomes are multiprotein complexes tasked with sensing endogenous or exogenous inflammatory signals and integrating this signal into a downstream response. Inflammasome activation has been implicated in a variety of pulmonary diseases, including pulmonary hypertension, bacterial pneumonia, COPD, and asthma. Of increasing interest is the contribution of inflammasome activation in the context of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Inflammasome activation in both the lung parenchyma and resident immune cells generates intereukin-1β (IL-1β) and IL-18, both of which drive the cascade of lung inflammation forward. Blockade of these responses has been shown to be beneficial in animal models and is a focus of translational research in the field. In this review, we will discuss the assembly and regulation of inflammasomes during lung inflammation, highlighting therapeutically viable effector steps. We will examine the importance of IL-1β and IL-18, two key products of inflammasome activation, in ALI, as well as the contribution of the pulmonary endothelial cell to this process. Finally, we will explore translational research moving toward anti-inflammasome therapies for ALI/ARDS and speculate toward future directions for the field.
Intranasal oxytocin has sympathoexcitatory effects on vascular tone in healthy males
Authors: Meusel M. , Herrmann M. , Machleidt F. , Franzen K. , Vonthein R. , Sayk F.
Published: December 2020

Oxytocin appears to be involved in the neuroendocrine regulation of sympathetic blood pressure (BP) homeostasis. In animals, intracerebral administration of oxytocin induces BP-relevant sympathetic activation. In humans, central nervous effects of oxytocin on BP regulation remain unclear. Intranasal administration supposedly delivers oligopeptides such as oxytocin directly to the brain. We investigated the effects of intranasal oxytocin on sympathetic vascular baroreflex function in humans using microneurographic techniques. In a balanced, double-blind crossover design, oxytocin or placebo was administered intranasally to 12 lean, healthy males (age 25 ± 4 yr). Muscle sympathetic nerve activity (MSNA) was assessed microneurographically before (presubstance), 30–45 min (postsubstance I), and 105–120 min (postsubstance II) after oxytocin administration. Baroreflex was challenged via graded infusions of vasoactive drugs, and correlation of BP with MSNA and heart rate (HR) defined baroreflex function. Experiments were conducted in the afternoon after a 5-h fasting period. After oxytocin, resting MSNA (burst rate and total activity) showed significant net increases from pre to postsubstance II compared with placebo [Δincrease = +4.3 ± 1.2 (oxytocin) vs. +2.2 ± 1.4 bursts/min (placebo), ANOVA; P < 0.05; total activity = 184 ± 11.5% (oxytocin) vs. 121 ± 14.3% (placebo), ANOVA; P = 0.01). This was combined with a small but significant net increase in resting diastolic BP, whereas systolic and mean arterial BP or HR as well as baroreflex sensitivity at vasoactive drug challenge were not altered. Intranasally administered oxytocin induced vasoconstrictory sympathoactivation in healthy male humans. The concomitant increase of diastolic BP was most likely attributable to increased vascular tone. This suggests oxytocin-mediated upward resetting of the vascular baroreflex set point at centers superordinate to the mere baroreflex-feedback loop.
Blunted sweating does not alter the rise in core temperature in people with multiple sclerosis exercising in the heat
Authors: Chaseling Georgia K. , Filingeri Davide , Allen Dustin , Barnett Michael , Vucic Steve , Davis Scott L. , Jay Ollie
Published: December 2020

The purpose of this study is to determine whether thermoregulatory capacity is altered by multiple sclerosis (MS) during exercise in the heat. Sixteen MS participants (EDSS: 2.9 ± 0.9; 47 ± 8 yr; 77.6 ± 14.0 kg) and 14 healthy control (CON) participants (43 ± 11 yr; 78.6 ± 17.0 kg) cycled at a heat production of 4 W·kg−1 for 60 min at 30°C, 30% relative humidity (RH) (Warm). A subset of eight MS (EDSS: 2.6 ± 0.5; 44 ± 8 yr; 82.3 ± 18.2 kg) and 8 CON (44 ± 12 yr; 81.2 ± 21.1 kg) also exercised at 35°C, 30% RH (Hot). Rectal temperature (Tre), mean skin (Tsk) temperature, and local sweat rate (LSR) on the upper back (LSRback) and forearm (LSRarm) were measured. All CON, and only 9 of 16 and 7 of 8 MS participants completed 60 min of exercise in Warm and Hot trials, respectively. All MS participants who were unable to complete exercise stopped with a ΔTre between 0.2 and 0.5°C. The time to reach a ΔTre of 0.2°C was similar (MS: 28 ± 15 min, CON: 32 ± 18 min; P = 0.51). For MS participants, completing 60-min of exercise in Warm, ΔTre ( P = 0.13), ΔTsk ( P = 0.45), LSRback ( P = 0.69), and LSRarm ( P = 0.54) was similar to CON, but ΔTb (body temperature) (MS: 0.16 ± 0.13°C, CON: 0.07 ± 0.06°C; P = 0.02) and onset time (MS: 16 ± 10 min, CON: 8 ± 5 min; P = 0.02) for sweating were greater in MS. Similarly, in Hot, ΔTre ( P = 0.52), ΔTsk ( P = 0.06), LSRback ( P = 0.59), and LSRarm ( P = 0.08) were similar, but ΔTb (MS: 0.19 ± 0.16°C, CON: 0.06 ± 0.04°C; P = 0.04) and onset time (MS: 13 ± 7 min, CON: 6 ± 3 min; P = 0.02) for sweating were greater in MS. Even at 35°C, a delayed sweating onset did not alter heat loss to sufficiently affect exercise-induced rises in core temperature. Heat intolerance with MS does not seem attributable to thermoregulatory impairments.
The complex role of prostaglandin E2-EP receptor signaling in wound healing
Authors: Gilman Kristy E. , Limesand Kirsten H.
Published: December 2020

Prostaglandins are critical lipid mediators involved in the wound healing response, with prostaglandin E2 (PGE2) being the most complex and exhibiting the most diverse physiological outputs. PGE2 signals via four G protein-coupled receptors, termed EP-receptors 1-4 that induce distinct signaling pathways upon activation and lead to an array of different outputs. Recent studies examining the role of PGE2 and EP receptor signaling in wound healing following various forms of tissue damage are discussed in this review.
Pre-locus coeruleus neurons in rat and mouse
Authors: Gasparini Silvia , Resch Jon M. , Gore Anuradha M. , Peltekian Lila , Geerling Joel C.
Published: December 2020

Previously, we identified a population of neurons in the hindbrain tegmentum, bordering the locus coeruleus (LC). We named this population the pre-locus coeruleus (pre-LC) because in rats its neurons lie immediately rostral to the LC. In mice, however, pre-LC and LC neurons intermingle, making them difficult to distinguish. Here, we use molecular markers and anterograde tracing to clarify the location and distribution of pre-LC neurons in mice, relative to rats. First, we colocalized the transcription factor FoxP2 with the activity marker Fos to identify pre-LC neurons in sodium-deprived rats and show their distribution relative to surrounding catecholaminergic and cholinergic neurons. Next, we used sodium depletion and chemogenetic activation of the aldosterone-sensitive HSD2 neurons in the nucleus of the solitary tract (NTS) to identify the homologous population of pre-LC neurons in mice, along with a related population in the central lateral parabrachial nucleus. Using Cre-reporter mice for Pdyn, we confirmed that most of these sodium-depletion-activated neurons are dynorphinergic. Finally, after confirming that these neurons receive excitatory input from the NTS and paraventricular hypothalamic nucleus, plus convergent input from the inhibitory AgRP neurons in the arcuate hypothalamic nucleus, we identify a major, direct input projection from the medial prefrontal cortex. This new information on the location, distribution, and input to pre-LC neurons provides a neuroanatomical foundation for cell-type-specific investigation of their properties and functions in mice. Pre-LC neurons likely integrate homeostatic information from the brainstem and hypothalamus with limbic, contextual information from the cerebral cortex to influence ingestive behavior.
Variable but not random: temporal pattern coding in a songbird brain area necessary for song modification
Authors: Palmer S. E. , Wright B. D. , Doupe A. J. , Kao M. H.
Published: December 2020

This paper shows that bursts of spikes in the songbird brain during practice carry information about the output motor pattern. The brain’s code for song changes with social context, in performance versus practice. Synergistic combinations of spiking and silence code for time in the bird’s song. This is one of the first uses of information theory to quantify neural information about a motor output. This activity may guide changes to the song.
Sensitivity of express saccades to the expected value of the target
Authors: Shams-Ahmar Mohammad , Thier Peter
Published: December 2020

Express saccades are the fastest visually driven way of shifting gaze to targets of interest. We examined whether the pathway underlying these saccades has access to information on the value of saccade targets. We found that not only regular saccades but also express saccades occur earlier in case of higher expectations of reward. Yet, the sensitivity of express saccades to reward decreases linearly when approaching the earliest possible reaction time.
The effects of a spaceflight analog with elevated CO2 on sensorimotor adaptation
Authors: Banker Lauren A. , Salazar Ana Paula , Lee Jessica K. , Beltran Nichole E. , Kofman Igor S. , De Dios Yiri E. , Mulder Edwin , Bloomberg Jacob J. , Mulavara Ajitkumar P. , Seidler Rachael D.
Published: December 2020

This is the first bed rest campaign examining sensorimotor adaptation and savings in response to the combined effect of HDBR + CO2 and to observe signs of spaceflight-associated neuro-ocular syndrome (SANS) in HDBR participants. Our findings suggest that HDBR + CO2 alters the way that individuals engage in sensorimotor processing. Individuals who developed signs of SANS seem to rely more on implicit rather than cognitive processing of adaptive behaviors than subjects who did not present signs of SANS.
Using asymmetry to your advantage: learning to acquire and accept external assistance during prolonged split-belt walking
Authors: Sánchez Natalia , Simha Surabhi N. , Donelan J. Maxwell , Finley James M.
Published: December 2020

Split-belt treadmill adaptation can be seen as a process where people learn to acquire positive work from the treadmill to reduce energetic cost. Though we know what people should do to reduce energetic cost, this strategy is not observed during adaptation studies. We extended the duration of adaptation and show that people continuously adapt their gait to acquire positive work from the treadmill to reduce energetic cost. This process requires longer exposure than traditionally allotted.
Closed-Loop neuromodulation for clustering neuronal populations
Authors: Faramarzi Sadegh , Netoff Théoden I.
Published: December 2020

Here, we present a closed-loop controller to desynchronize neurons in brain slices by inducing clusters using a single electrode using calcium imaging feedback. Phase of neurons are estimated in real time, and from the phase response curve stimulation is applied to achieve target phase differences. This method is an alternative to coordinated reset and is a novel therapy that could be used to disrupt synchronous neuronal oscillations thought to be the mechanism underlying Parkinson’s disease.
Vestibular function modulates the impact of nGVS on postural control in older adults
Authors: Nooristani Mujda , Bigras Charlotte , Lafontaine Louise , Bacon Benoit-Antoine , Maheu Maxime , Champoux François
Published: December 2020

The present study is the first study to investigate the impact of vestibular function on the improvement of postural control induced by nGVS in older adults and to compare the improvement of postural control of older adults with and without vestibular impairment. Our results also suggest that nGVS is beneficial for all older adults, and even more for those with a vestibular impairment. Therefore, it could be an approach to reduce falls.
Evidence for sparse C-tactile afferent innervation of glabrous human hand skin
Authors: Watkins Roger Holmes , Dione Mariama , Ackerley Rochelle , Backlund Wasling Helena , Wessberg Johan , Löken Line S.
Published: December 2020

Human touch is encoded by low-threshold mechanoreceptors, including myelinated Aβ afferents and unmyelinated C-tactile (CT) afferents. CTs are abundant in hairy skin and are thought to code gentle, stroking touch that signals positive affective interactions. CTs have never been described in human glabrous skin, yet we show evidence of their existence on the hand, albeit at a relatively low density. Glabrous skin CTs may provide modulatory reinforcement of gentle tactile interactions during touch using the hands.