bluuebunny/crossref_metadata_2025 huggingface dataset:
466 PREVALENCE AND IMPACT OF FRAILTY IN PATIENTS HOSPITALISED WITH COVID-19. THE SALFORD EXPERIENCE IN WAVES 1 AND 2
Authors: Khan A , Espinoza F R , Kneen T , Dafnis A , Allafi H , Carter B , Narro-Vidal M , Short R , Price A , Upton R , Vilches-Moraga A
Published: June 2021

Introduction

The COVID-19 pandemic has had an extensive impact on the frail older population, with significant rates of COVID-related hospital admissions and deaths amongst this vulnerable group. There is little evidence comparing the prevalence and impact of frailty amongst patients hospitalised with COVID-19 in wave 1 vs wave 2 of the pandemic.

Methods

Prospective observational study of all consecutive patients admitted to Salford Royal NHS Foundation Trust (SRFT) between 27th February and 28th of April 2020 (wave 1), and 1st October to 10th November 2020 (wave 2) with a diagnosis of COVID-19. The primary endpoint was in-hospital mortality. Patient demographics, co-morbidities, biochemical parameters, and frailty (using the Clinical Frailty Scale, score 1–4 = not frail, score 5–9 = frail) were collected. A Cox proportional hazards model associating wave and frailty with mortality was used. A logistic regression model was used to associate patient characteristics with wave. Both models adjusted for patient characteristics.

Results

A total of 700 patients were included (N = 429, wave 1; N = 271, wave 2). In wave 1, 42% (N = 180) were female; median age was 72; 37% (N = 160) were non-survivors, 49% (N = 212) were frail (CFS 5–9). In wave 2, 38% (N = 104) were female; median age was 73; 30% (N = 80) were non-survivors, 39% (N = 106) were frail. There was a reduction in mortality in wave 2, aHR = 0.71 (95% CI 0.53–0.94). Frailty was associated with increased mortality, after adjustment for age, wave and other patient characteristics. Patients were more frail in wave 1, and the effect of frailty was more pronounced in wave 1 vs wave 2.

Conclusion

Frailty is highly prevalent amongst patients of all ages admitted to SRFT with COVID-19. Higher scores of frailty are associated with increased mortality.
483 IMPROVING THE PROVISION OF REGIONAL GERIATRIC MEDICINE TEACHING DURING THE COVID-19 PANDEMIC
Authors: Smith N , Owen C , Mankelow T
Published: June 2021

Introduction

In Wessex Deanery, prior to the COVID-19 pandemic, Geriatric Medicine trainees from 10 NHS trusts attended face-to-face regional teaching sessions. In response to the pandemic, this teaching was suspended to reduce disruption in service provision and support social distancing. There was a clear need to reintroduce teaching for continued professional development and trainee progression.

Methods

In July 2020, Geriatric Medicine trainees in Wessex completed a questionnaire survey to identify their desire for socially distanced teaching and an acceptable format for delivery. Two half-day pilot teaching sessions via MS Teams were organised in September and October 2020. Trainees provided feedback via a questionnaire survey about the relevance and quality of teaching, and to identify any barriers to attendance. Subsequently, a monthly full-day virtual teaching programme was implemented. We reported reflections of our experiences on our trainee website to support future sessions.

Results

All trainees (n = 15) were eager for regional teaching to recommence through socially distanced education. Trainees had a preference for MS Teams, which can support interactive teaching. Attendance to the pilot sessions exceeded previous face-to-face sessions. 19 trainees attended the first session; 17 provided feedback. 28 trainees attended the second session; 12 provided feedback. Feedback was overwhelmingly positive; all reported the sessions were interesting and 82% (n = 14) that they would lead to changes in their practice. Some trainees expressed that full-day sessions would enhance curriculum coverage. 94% (n = 16) were positive of the virtual platform; it reduced travel and sessions could be recorded. Local trainees attended the second session in-person, which enhanced interactivity.

Conclusion

Virtual teaching has been successful in Wessex Deanery, with high attendance and positive feedback. Trainees can engage remotely without the need for travel and disruption. After the pandemic we hope to develop a regional teaching programme integrating virtual and face-to-face sessions to improve attendance and accessibility.
499 DEVELOPING A NOVEL TEACHING PROGRAMME FOR PHYSICIAN ASSOCIATE STUDENTS WITHIN ELDERLY MEDICINE
Authors: Mottaghi-Taromsari S , Wileman L
Published: June 2021

Introduction

The Physician Associate course has been running in the North West since 2016. As such, the format and layout of clinical placements for its students are still in their relative infancy. First year students, similar to third year medical students, begin clinical placement after an intensive lecture series at the University. Placements at Wythenshawe hospital typically involved an initial and closing meeting with their supervisor with little teaching activity organised specifically for them. We therefore set out to devise a formal teaching programme within their elderly care attachment to better address their learning needs.

Methods

We devised a programme for the placement involving a formal induction, orientation and then rotation through different elements of the elderly medicine faculty. The students spent 4 weeks in total in 3 different clinical areas to obtain different experiences. Formal teaching was arranged once per week with a clinician to cover topics relevant to geriatrics and general medicine. Feedback forms were used to assess the students’ views on the quality of the induction and teaching. A pre-placement questionnaire was used at the start to assess understanding of frailty and confidence with assessing falls. This was then repeated at the end of the placement to evaluate progression.

Results

From the initial pilot involving 3 cohorts (10 students total), 90% of the students rated the placement positively as a learning opportunity with 100% commending the organisation and structure of the programme. 100% of students rated the content and delivery as good for the organised teaching sessions. Understanding of frailty and confidence in assessing falls also saw marked improvements over the course of the placement.

Conclusion

We have demonstrated how a better structured teaching programme is valued by the physician associate students and will now proceed to develop and expand this model in elderly medicine and beyond.
502 OUTCOMES OF HOSPITALISED PATIENTS WITH COVID-19 SIX MONTHS AFTER INDEX ADMISSION
Authors: Tullo E , Dotchin C , Jaiswal S
Published: June 2021

Introduction

Early outcomes for hospitalised patients with covid-19, including admissions to critical care and mortality have been widely published. Less is known about the longer-term patient outcomes such as readmissions, deaths after discharge and level of care required on discharge.

Methods

Following an audit of 360 consecutive admissions of patients with covid-19 requiring level 1 inpatient care in spring 2020, we collated data about mortality, readmissions, and residential status for the same cohort at six months after index admission.

Results

The cohort had a median age of 78: 70% survived to discharge. Median length of stay was nine days (range 1–90). Of 252 patients discharged, a further 35 (14%) had died by six-month follow-up. 95 patients (38%) required at least one further hospital admission in the following six-month period. 40 (16%) of discharged patient required increased support, defined as new or increased package of care or an alternative interim or permanent change of residence. (Table 1). Table 1 emailed separately as will not transfer into this space Of the 40 patients requiring increased support on discharge, 7 (18%) died, 15 (38%) returned to their preadmission residential status, and 17 (43%) still required increased support.

Conclusions

Covid-19 has a high mortality rate in those admitted to hospital. Patients receiving level 1 care in hospital and surviving to discharge have a high risk of readmission or death in the following six-months. For those requiring increased support on discharge, the majority do not return to their pre-admission residential status.
511 DO ORAL NUTRITIONAL SUPPLEMENTS IMPROVE QUALITY OF LIFE IN THE FRAIL ELDERLY- A SYSTEMATIC REVIEW
Authors: Ryan C , Hynd I
Published: June 2021

Background

Oral nutritional supplements (ONS) are regularly used in older frail adults to help reduced oral intake, recovery from acute illness and weight gain. As, many frailer patients have limited life expectancies the priority for treatment should be improving quality of life (QoL). We set out to find if ONS increase QoL in the frail elderly adult.

Method

We searched Embase, Medline and OVID databases for using terms for ONS, frail older adults and QoL. The two authors independently reviewed all papers with any dispute was resolved by discussion. Each paper was then reviewed by both authors to extract data and determine bias before collation.

Results

The search returned 516 papers. Each paper was briefly reviewed to check for relevance leaving 65 papers for detailed review of which 8 papers were included. Two systematic reviews were included. One was unable to draw conclusions from the 3 papers (out of 17) that included QoL as the graded evidence was too poor. The other showed no impact on QoL (in the 2 out of 12 papers that included QoL) in patients post hip fracture receiving ONS. One paper interviewed frail elderly patients about the perceived benefits of their ONS. Nursing home residents perceived that ONS improved their ability to see family which was inferred as improving QoL. Three papers assessed ONS in conjunction with physical exercise. Two showed an improvement in quality of life in the ONS group despite controls also receiving a physical exercise programme. Two papers assessed the impact of ONS on patients discharged from hospital and those chronically unwell- neither showed any difference in QoL.

Discussion

Quality of life has been a neglected area of study when assessing the impact of ONS on frail elderly patients. When used in conjunction with physical exercise it seems to have a positive effect.
512 A CASE OF AN IDIOPATHIC ACQUIRED HEMOPHILIA A IN AN ELDERLY WOMAN
Authors: Phyu E E , Than H P , Hayward M
Published: June 2021

Introduction

Acquired Hemophilia is a bleeding diathesis caused by autoantibodies that interfere with factor VIII (FVIII). Reasons for autoantibodies production are not clear but may be related to gene polymorphisms and/or CD4+ T lymphocytes. 1.3 to 1.5 cases per million population per year are reported in the UK. Half of the cases are secondary to malignancy, pregnancy related conditions, connective tissue disorders or drug reactions while the rest are idiopathic.

Case Report

We report a case of an acquired hemophilia A in an 86-year-old lady with underlying type 2 diabetes, hypertension, and cognitive impairment, being treated as the left lower limb cellulitis with antibiotics. She was found to have a sudden hemoglobin drop and her CT (Abdomen) confirmed a spontaneous intra-abdominal hematoma. Clotting profile showed prolonged APTT to 168.5 seconds, being not corrected at mixing study, with normal PT and INR. The FVIII assay was reduced to 18.4 iU/dL with FVIII inhibitor concentration of 0.7 Bu. Viral and autoimmune screenings were negative. The idiopathic acquired hemophilia A was diagnosed. Red blood cell transfusions, bypassing agents (FEIBA) and oral tranexamic acid were given for acute bleeding episode. Concomitantly, oral prednisolone was used to reduce the inhibitor levels. Repeated FVIII assay showed 121 iU/dL and 199iU/dL on day 6 and 12, respectively. Steroid was continued for the next 4 weeks and then gradually tapered. No further bleeding episode was noted.

Conclusion

The diagnosis of acquired hemophilia should be considered in any elderly patient with prolonged APTT. Mixing study is to measure the presence of inhibitors of coagulation or to detect coagulation factor deficiency. Quantitative coagulation factor assays and Bethesda Assays are performed for definitive diagnosis. Immunosuppressive regimens are the mainstay treatment. However, premorbid conditions and co-morbidities should be taken into consideration before initiating the aggressive immunosuppressive therapy in the elderly patients.
513 THE INFLUENCE OF FRAILTY ON OUTCOMES FOR OLDER ADULTS ADMITTED TO HOSPITAL WITH BENIGN BILIARY AND PANCREATIC DISEASE
Authors: Thomas M , Baltatzis M , Price A , Pearce L , Fox J , Vilches-Moraga A
Published: June 2021

Introduction

The prevalence and complications of biliary disease increase with age. We describe the prevalence of frailty in older patients hospitalised with benign biliary and pancreatic disease and establish its association with mortality and duration of hospital stay.

Methods

Prospective observational cohort study of patients aged 75 years and over admitted with a diagnosis of acute biliary disease to a surgical hospital unit between 17/09/2014 and 20/03/2017. Clinical Frailty Scale (CFS) score was recorded on admission.

Results

We included 200 patients with a median age of 82 (75–99), 60% females, 89% lived in their homes, 154 (77%) were independent for personal and 99 (49.5%) for instrumental ADLs, 95% mobilised independently, 17.5% had memory impairment and 8% low mood. Acute cholecystitis was the most common diagnosis (43%) followed by acute cholangitis (36%) and acute pancreatitis (21%). 99 patients were non-frail (NF = CFS 1–4) and 101 were frail (F = CFS ≥5). 104 patients received medical treatment only. Surgery was more common in non-frail (F 2% vs. NF 11%), percutaneous drainage more frequently carried out in frail patients (15% vs. NF 5%) and endoscopic cholangiopancreatography (ERCP) was similar in both groups (F 32%vs. NF 31%). Frailty was associated with worse clinical outcomes in F vs. NF: functional deconditioning (34% vs. 11%), increased care level (19% vs 3%), length of stay (12 vs. 7 days), 90-day (8% vs. 3%) and 1 year-mortality (48% vs. 24%).

Conclusion

Half of patients in our cohort of older adults hospitalised with acute biliary disease were frail. Higher scores of frailty are associated with increased mortality. Compared with non-frail patients, individuals living with frailty were less likely to undergo surgical treatment, spent longer in hospital and were less likely to remain alive at 12 months after hospital discharge.
558 PREVALENCE AND IMPACT OF FRAILTY IN PATIENTS HOSPITALISED WITH COVID-19. THE SALFORD EXPERIENCE IN WAVES 1 AND 2
Authors: Khan A , Espinoza F R , Kneen T , Dafnis A , Allafi H , Carter B , Narro-Vidal M , Short R , Price A , Upton R , Vilches-Moraga A
Published: June 2021

Introduction

The COVID-19 pandemic has had an extensive impact on the frail older population, with significant rates of COVID-related hospital admissions and deaths amongst this vulnerable group. There is little evidence of frailty prevalence amongst patients hospitalised with COVID-19, nor the impact of frailty on their survival.

Methods

Prospective observational study of all consecutive patients admitted to Salford Royal NHS Foundation (SRFT) Trust between 27th February and 28th April 2020 (wave 1), and 1st October to 10th November 2020 (wave 2) with a diagnosis of COVID-19. The primary endpoint was in-hospital mortality. Patient demographics, co-morbidities, admission level disease severity (estimated with CRP) and frailty (using the Clinical Frailty Scale, score 1–3 = not frail, score 4–9 = frail) were collected. A Cox proportional hazards regression model was used to assess the time to mortality.

Results

A total of 693 (N = 429, wave 1; N = 264, wave 2) patients were included, 279 (N = 180, 42%, wave 1; N = 104, 38%, wave 2) were female, and the median age was 72 in wave 1 and 73 in wave 2. 318 (N = 212, 49%, wave 1; N = 106, 39%, wave 2) patients presenting were frail. There was a reduction in mortality in wave 2, adjusted Hazard ratio (aHR) = 0.60 (95%CI 0.44–0.81; p = 0.001). There was an association between frailty and mortality aHR = 1.57 (95%CI 1.09–2.26; p = 0.015).

Conclusion

Frailty is highly prevalent amongst patients of all ages admitted to SRFT with COVID-19. Higher scores of frailty are associated with increased mortality.
603 CHALLENGES IN THE MANAGEMENT OF SEVERE ORTHOSTATIC HYPOTENSION ASSOCIATED WITH SUPINE HYPERTENSION IN A PATIENT WITH AUTONOMIC DYSFUNCTION ON BACKGROUND OF NASOPHARYNGEAL CARCINOMA AND TYPE II DIABETES MELLITUS
Authors: Rachel Q M N , Mamun K , Nguyen M H
Published: June 2021

Introduction

Combined chemotherapy and radiotherapy increases long term survival in patients with nasopharyngeal carcinoma. However, radiotherapy of the carotid sinus or brain stem can evolve labile hypertension and orthostatic intolerance from chronic baroreflex failure. Diabetes would also cause this neuropathy. Management of patients with Supine hypertension-Orthostatic hypotension can be very challenging.

Methods

A case report was done on a 71-year-old man with metastatic nasopharyngeal carcinoma status post radiation therapy who was admitted with severe supine hypertension-orthostatic hypotension. Patient was managed with both non-pharmacological and pharmacological methods, and monitored for postural symptoms, complications of severe supine hypertension—which has been linked to left ventricular hypertrophy and kidney dysfunction, and placed on 24 hour ambulatory blood pressure monitoring to aid in management so as to prevent hypertension induced organ damage.

Results

This review outlines the pathophysiology of Supine hypertension-Orthostatic hypotension, treatment complications and potential management strategies recommendations for this group of patients. It revealed the benefit of having a 24 hour ambulatory blood pressure monitoring, which provides insight on the timing and magnitude of an individual’s blood pressure fluctuations throughout the day so as to further guide management.

Conclusion

Chronic baroreflex failure is a late sequela of neck irradiation for naso-pharyngeal carcinoma due to accelerated atherosclerosis in the region of the carotid sinus baroreceptor. Treatment goal is achieved with adequate control of pre-syncopal symptoms and prevention of long term complications. Non-pharmacological interventions remain the first line of therapy, followed by pharmacological interventions as necessary. Nonetheless, management of blood pressure in these elderly patients with baroreflex dysfunction remains challenging and should be individualized. Moving forward, a prospective study on the incidence of late onset, iatrogenic baroreflex failure as a late complication of neck irradiation and its particular relationship to carotid arterial rigidity should be conducted to increase awareness, timely diagnosis and management of the condition among physicians.
The Role of Copper and Zinc in Irritable Bowel Syndrome: A Mendelian Randomization Study
Authors: Hujoel Isabel A , Hujoel Margaux L A
Published: June 2021

Irritable bowel syndrome (IBS) has been associated with copper and zinc imbalance and a zinc-deficient diet. Mendelian randomization was used in this study to evaluate if genetically determined copper and zinc levels play a causal role in the development of IBS. Three single-nucleotide polymorphisms (SNPs; rs1175550, rs2769264, and rs2769270) associated with erythrocyte copper levels, and 3 SNPs associated with erythrocyte zinc levels (rs11638477, rs1532423, and rs2120019) in the Australian Twin Study (1993–1996 and 2001–2005) were used as instrumental variables for levels of these metals. The association of these SNPs with IBS was tested using summary statistics computed from data on 340,331 individuals from the UK Biobank, 5,548 of whom had IBS (2006–2010). Genetically predicted high serum copper levels were associated with a lower risk of IBS (odds ratio = 0.89; 95% confidence interval: 0.80, 0.98). Genetically predicted, high serum zinc levels were nonsignificantly associated with a higher risk of IBS (odds ratio = 1.06; 95% confidence interval: 0.95, 1.18). Sensitivity analysis did not suggest the presence of pleiotropy. These results suggest that high erythrocyte copper levels may be protective against IBS development. Targeting higher levels, therefore, may provide an avenue to reduce the likelihood of IBS development in high-risk individuals.
Latinx Modernism and the Spirit of Latinoamericanismo
Authors: Cutler John Alba
Published: June 2021

Newspapers were the primary literary institutions of Latinx modernism, and attending more centrally to newspaper and other periodical literature changes the way we understand Latinx literary history. It demonstrates not only the generic and formal dynamism of Latinx writing but also how thoroughly embedded that writing has always been in hemispheric currents of thought and textual circulation. In this essay, I give an account of how Latinx modernism contributes to and transforms the fields of Latinx literature, modernist studies, and Latin American studies. I describe the print-cultural archive of Latinx modernism and justify my use of the term Latinx based on the transnational identifications of newspaper literature pages during this period. I then outline the problems and potentiality presented by the Latinity of Latinx writing, building on the work of Latin American decolonial theorists. Relying on examples from the archive, I show how Latinx modernism engages what I am calling the spirit of Latinoamericanismo and in the process transforms our conception of American modernity, showing it to be inextricable from coloniality. The spirit of Latinoamericanismo figures the oppositional potential of Latinx modernist literature, including its contradictions and limits.
Executive Function Assigns Value to Novel Goal-Congruent Outcomes
Authors: McDougle Samuel D , Ballard Ian C , Baribault Beth , Bishop Sonia J , Collins Anne G E
Published: June 2021

People often learn from the outcomes of their actions, even when these outcomes do not involve material rewards or punishments. How does our brain provide this flexibility? We combined behavior, computational modeling, and functional neuroimaging to probe whether learning from abstract novel outcomes harnesses the same circuitry that supports learning from familiar secondary reinforcers. Behavior and neuroimaging revealed that novel images can act as a substitute for rewards during instrumental learning, producing reliable reward-like signals in dopaminergic circuits. Moreover, we found evidence that prefrontal correlates of executive control may play a role in shaping flexible responses in reward circuits. These results suggest that learning from novel outcomes is supported by an interplay between high-level representations in prefrontal cortex and low-level responses in subcortical reward circuits. This interaction may allow for human reinforcement learning over arbitrarily abstract reward functions.
Genetic Influences on Longitudinal Trajectories of Cortical Thickness and Surface Area during the First 2 Years of Life
Authors: Xia Kai , Schmitt J Eric , Jha Shaili C , Girault Jessica B , Cornea Emil , Li Gang , Shen Dinggang , Styner Martin , Gilmore John H
Published: June 2021

Genetic influences on cortical thickness (CT) and surface area (SA) are known to vary across the life span. Little is known about the extent to which genetic factors influence CT and SA in infancy and toddlerhood. We performed the first longitudinal assessment of genetic influences on variation in CT and SA in 501 twins who were aged 0–2 years. We observed substantial additive genetic influences on both average CT (0.48 in neonates, 0.37 in 1-year-olds, and 0.44 in 2-year-olds) and total SA (0.59 in neonates, 0.74 in 1-year-olds, and 0.73 in 2-year-olds). In addition, we found strong heritability of the change in average CT (0.49) from neonates to 1-year-olds, but not from 1- to 2–year-olds. Moreover, we found strong genetic correlations for average CT (rG = 0.92) between 1- and 2-year-olds and strong genetic correlations for total SA across all timepoints (rG = 0.96 between neonates and 1-year-olds, rG = 1 between 1- and 2-year-olds). In addition, we found CT and SA are strongly genetic correlated at birth, but weaken over time. Overall, results suggest a dynamic genetic relationship between CT and SA during first 2 years of life and provide novel insights into how genetic influences shape the cortical structure during early brain development.
Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults
Authors: Johnson Stuart , Lavergne Valéry , Skinner Andrew M , Gonzales-Luna Anne J , Garey Kevin W , Kelly Ciaran P , Wilcox Mark H
Published: June 2021

This clinical practice guideline is a focused update on management of Clostridioides difficile infection (CDI) in adults specifically addressing the use of fidaxomicin and bezlotoxumab for the treatment of CDI. This guideline was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline is intended for use by healthcare professionals who care for adults with CDI, including specialists in infectious diseases, gastroenterologists, hospitalists, pharmacists, and any clinicians and healthcare providers caring for these patients. The panel’s recommendations for the management CDI are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the management of CDI in adults. The panel followed a systematic process which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.
Estimation of nonstationary nonparametric regression model with multiplicative structure
Authors: Chen Likai , Smetanina Ekaterina , Wu Wei Biao
Published: June 2021

This paper presents a multiplicative nonstationary nonparametric regression model which allows for a broad class of nonstationary processes. We propose a three-step estimation procedure to uncover the conditional mean function and establish uniform convergence rates and asymptotic normality of our estimators. The new model can also be seen as a dimension-reduction technique for a general two-dimensional time-varying nonparametric regression model, which is especially useful in small samples and for estimating explicitly multiplicative structural models. We consider two applications: estimating a pricing equation for the US aggregate economy to model consumption growth and estimating the shape of the monthly risk premium for S&P 500 Index data.
Neurogenesis in the adult Drosophila brain
Authors: Crocker Kassi L , Marischuk Khailee , Rimkus Stacey A , Zhou Hong , Yin Jerry C P , Boekhoff-Falk Grace
Published: June 2021

Neurodegenerative diseases such as Alzheimer’s and Parkinson’s currently affect ∼25 million people worldwide. The global incidence of traumatic brain injury (TBI) is estimated at ∼70 million/year. Both neurodegenerative diseases and TBI remain without effective treatments. We are utilizing adult Drosophila melanogaster to investigate the mechanisms of brain regeneration with the long-term goal of identifying targets for neural regenerative therapies. We specifically focused on neurogenesis, i.e., the generation of new cells, as opposed to the regrowth of specific subcellular structures such as axons. Like mammals, Drosophila have few proliferating cells in the adult brain. Nonetheless, within 24 hours of a penetrating traumatic brain injury (PTBI) to the central brain, there is a significant increase in the number of proliferating cells. We subsequently detect both new glia and new neurons and the formation of new axon tracts that target appropriate brain regions. Glial cells divide rapidly upon injury to give rise to new glial cells. Other cells near the injury site upregulate neural progenitor genes including asense and deadpan and later give rise to the new neurons. Locomotor abnormalities observed after PTBI are reversed within 2 weeks of injury, supporting the idea that there is functional recovery. Together, these data indicate that adult Drosophila brains are capable of neuronal repair. We anticipate that this paradigm will facilitate the dissection of the mechanisms of neural regeneration and that these processes will be relevant to human brain repair.
Association of Markers of Inflammation, the Kynurenine Pathway and B Vitamins with Age and Mortality, and a Signature of Inflammaging
Authors: Dugué Pierre-Antoine , Hodge Allison M , Ulvik Arve , Ueland Per M , Midttun Øivind , Rinaldi Sabina , MacInnis Robert J , Li Sherly X , Meyer Klaus , Navionis Anne-Sophie , Flicker Leon , Severi Gianluca , English Dallas R , Vineis Paolo , Tell Grethe S , Southey Melissa C , Milne Roger L , Giles Graham G
Published: June 2021

Background

Inflammation is a key feature of aging. We aimed to (i) investigate the association of 34 blood markers potentially involved in inflammatory processes with age and mortality and (ii) develop a signature of “inflammaging.”

Methods

Thirty-four blood markers relating to inflammation, B vitamin status, and the kynurenine pathway were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (median age = 59 years) and follow-up (median age = 70 years). Associations with age and mortality were assessed using linear and Cox regression, respectively. A parsimonious signature of inflammaging was developed and its association with mortality was compared with 2 marker scores calculated across all markers associated with age and mortality, respectively.

Results

The majority of markers (30/34) were associated with age, with stronger associations observed for neopterin, cystatin C, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), several markers of the kynurenine pathway and derived indices KTR (kynurenine/tryptophan ratio), PAr index (ratio of 4-pyridoxic acid and the sum of pyridoxal 5′-phosphate and pyridoxal), and HK:XA (3-hydroxykynurenine/xanthurenic acid ratio). Many markers (17/34) showed an association with mortality, in particular IL-6, neopterin, C-reactive protein, quinolinic acid, PAr index, and KTR. The inflammaging signature included 10 markers and was strongly associated with mortality (hazard ratio [HR] per SD = 1.40, 95% CI: 1.24–1.57, p = 2 × 10−8), similar to scores based on all age-associated (HR = 1.38, 95% CI: 1.23–1.55, p = 4 × 10−8) and mortality-associated markers (HR = 1.43, 95% CI: 1.28–1.60, p = 1 × 10−10), respectively. Strong evidence of replication of the inflammaging signature association with mortality was found in the Hordaland Health Study.

Conclusion

Our study highlights the key role of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. A signature of inflammaging based on 10 markers was strongly associated with mortality.
Sex-Specific Difference in Dynamic Balance Following Total Hip Replacement
Authors: Queen Robin M , Schmitt Daniel
Published: June 2021

Background and Objectives

Total hip arthroplasty (THA) is a common surgical procedure in older adults (65 years or older). THA has high patient satisfaction, but little is known about balance and mobility limitations after surgery and if outcomes are sex-specific. This study was aimed to evaluate post-THA asymmetry during unilateral standing and a dynamic balance and reach test and test the hypotheses that balance performance would be decreased on the surgical limb and that balance deficits would be greater in women than in men.

Research Design and Methods

Primary, unilateral THA (70 male, 57 female) patients completed a bilateral 10-s single-leg stance test. Sixty male but only 34 female participants could maintain unilateral balance for 10 s or greater. The cohort who successfully completed the 10-s single-limb stance test then completed a Lower Quarter Y-Balance Test in which the maximum anterior (ANT), posteromedial (PM), and posterolateral reach distances were obtained bilaterally and used to calculate the asymmetry score. All variables were compared using a mixed-model repeated-measures analysis of variance (sex by limb), while independent samples t tests were used to assess sex-specific asymmetry.

Results

Women failed single-leg stance at a higher rate than men (85.7% vs 59.6%; p = .001). Reach distance was different between limbs for all reach directions (p < .004) with greater reach distance on the nonoperative limb for all patients. Men had a greater reach distance in the ANT (p = .004) and PM (p = .006) directions.

Discussion and Implications

These results indicate that post-THA, the operative limb and female patients have greater balance limitations. These results are novel and reveal sex-specific patterns that emphasize the need for sex-specific postoperative rehabilitation programs to improve long-term outcomes, especially in older adults with muscle weakness and balance deficits.
Maximum covariance direction method for unconventional seismic sources
Authors: Zhu Juan , Chen Xiaohan , Wen Lianxing
Published: June 2021

We propose a new array covariance matrix analysis method, named ‘maximum covariance direction method’ (MCD method), to detect and locate unconventional seismic sources of weak signals without clear onsets. The MCD method builds a normalized-covariance matrix of time-shifted seismic waveforms recorded in a seismic array and determines the existence of source based on the consistency of the maximum covariance direction with the theoretical prediction. Synthetic tests demonstrate effectiveness of the MCD method in detecting one and multiple isolated sources with low signal-to-noise ratios. As a data application, we study 1-hr long-period tremors (LPTs) around Aso Volcano of Japan in 2014 November 24. A total of 26 LPTs are detected near the Naka-dake first crater of Aso Volcano, with the uncertainties of source location of about 7 km. Using the recorded background noise at the seismic stations, we show that the MCD method can detect LPTs even when the LPT signals are buried in the background noise and become indiscernible in the seismic data. Unlike traditional methods that employ the coherent features of seismic signals for source detection, the MCD method places emphases on both the coherence of seismic signals and consistency of the direction of the coherent signals from a potential source location. The synthetic tests and data application indicate that the MCD method provides a good alternative to other traditional methods for detecting and locating unconventional seismic sources, with a major improvement of avoiding source misidentification in the presence of strong incoherent signals.
Novel xylan degrading enzymes from polysaccharide utilizing loci of Prevotella copri DSM18205
Authors: Linares-Pastén Javier A , Hero Johan Sebastian , Pisa José Horacio , Teixeira Cristina , Nyman Margareta , Adlercreutz Patrick , Martinez M Alejandra , Karlsson Eva Nordberg
Published: June 2021

Prevotella copri is a bacterium that can be found in the human gastrointestinal tract. The role of P. copri in the GIT is unclear, and elevated numbers of the microbe have been reported both in dietary fiber-induced improvement in glucose metabolism but also in conjunction with certain inflammatory conditions. These findings raised our interest in investigating the possibility of P. copri to grow on xylan, and identify the enzyme systems playing a role in digestion of xylan-based dietary fibers. Two xylan degrading polysaccharide utilizing loci (PUL10 and 15) were found in the genome, with three and eight glycoside hydrolase (GH) -encoding genes, respectively. Three of them were successfully produced in Escherichia coli: One extracellular enzyme from GH43 (subfamily 12, in PUL10, 60 kDa) and two enzymes from PUL15, one extracellular GH10 (41 kDa), and one intracellular GH43 (subfamily 137 kDa). Based on our results we propose that in PUL15, GH10 (1) is an extracellular endo-1,4-β-xylanase, that hydrolyses mainly glucuronosylated xylan polymers to xylooligosaccharides (XOS); while, GH43_1 in the same PUL, is an intracellular β-xylosidase, catalysing complete hydrolysis of the XOS to xylose. In PUL10, the characterized GH43_12 is an arabinofuranosidase, with a role in degradation of arabinoxylan, catalysing removal of arabinose-residues on xylan.
Sexual Selection and Introgression in Avian Hybrid Zones: Spotlight onManacus
Authors: Bennett Kevin F P , Lim Haw Chuan , Braun Michael J
Published: June 2021

Hybrid zones offer a window into the processes and outcomes of evolution, from species formation or fusion to genomic underpinnings of specific traits and isolating mechanisms. Sexual selection is believed to be an important factor in speciation processes, and hybrid zones present special opportunities to probe its impact. The manakins (Aves, Pipridae) are a promising group in which to study the interplay of sexual selection and natural hybridization: they show substantial variation across the family in the strength of sexual selection they experience, they readily hybridize within and between genera, and they appear to have formed hybrid species, a rare event in birds. A hybrid zone between two manakins in the genus Manacus is unusual in that plumage and behavioral traits of one species have introgressed asymmetrically into populations of the second species through positive sexual selection, then apparently stalled at a river barrier. This is one of a handful of documented examples of asymmetric sexual trait introgression with a known selective mechanism. It offers opportunities to examine reproductive isolation, introgression, plumage color evolution, and natural factors enhancing or constraining the effects of sexual selection in real time. Here, we review previous work in this system, propose new hypotheses for observed patterns, and recommend approaches to test them.
All the World’s a Stage: US Presidential Narcissism and International Conflict
Authors: Harden John P
Published: June 2021

How do leaders matter? What do leaders want? Grandiose narcissism provides a pathway to understanding how personality can impact a leader’s preference formation and foreign policy behavior. More narcissistic leaders will focus their efforts on maintaining their inflated self-image by selecting how they will fight on the world stage and who they will fight against. While most leaders will divert attention to easier won battles, more narcissistic leaders will prefer to fight against high-status states by themselves. This article introduces a new measure of US’ presidential narcissism, and finds support for the argument that more narcissistic US presidents prefer unilaterally initiating Great Power disputes using data from 1897–2008. A brief review of Theodore Roosevelt’s handling of the Venezuela Crisis of 1902–1903 is used as a plausibility probe of the theory’s causal mechanisms.
Sensitive Screening of New Psychoactive Substances in Serum Using Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry
Authors: Kleis Jan-Niklas , Hess Cornelius , Germerott Tanja , Roehrich Joerg
Published: June 2021

Analysis of new psychoactive substances (NPS) still poses a challenge for many institutions due to the number of available substances and the constantly changing drug market. Both new and well-known substances keep appearing and disappearing on the market, making it hard to adapt analytical methods in a timely manner. In this study we developed a qualitative screening approach for serum samples by means of liquid chromatography--quadrupole time-of-flight mass spectrometry. Samples were measured in data-dependent auto tandem mass spectrometry mode and identified by fragment spectra comparison, retention time and accurate mass. Approximately 500 NPS, including 195 synthetic cannabinoids, 180 stimulants, 86 hallucinogens, 26 benzodiazepines and 7 others were investigated. Serum samples were fortified to 1 ng/mL and 10 ng/mL concentrations to estimate approximate limits of identification (LOIs). Samples were extracted using solid-phase extraction with non-endcapped C18 material and elution in two consecutive steps. Benzodiazepines were eluted in the first step, while substances of other NPS subclasses were distributed among both extracts. To determine LOIs, both extracts were combined. Ninety-six percent (470/492) of investigated NPS were detected in 10 ng/mL samples and 88% (432/492) were detected in 1 ng/mL samples. Stimulants stood out with higher LOIs, possibly due to instability of certain methcathinone derivatives. However, considering relevant blood concentrations, the method provided sufficient sensitivity for stimulants as well as other NPS subclasses. Data-dependent acquisition was proven to provide high sensitivity and reliability when combined with an information-dependent preferred list, without losing its untargeted operation principle. Summarizing, the developed method fulfilled its purpose as a sensitive untargeted screening for serum samples and allows uncomplicated expansion of the spectral library to include thousands of targets.
Brassinolide inhibits flavonoid biosynthesis and red-flesh coloration via the MdBEH2.2–MdMYB60 complex in apple
Authors: Wang Yicheng , Mao Zuolin , Jiang Huiyan , Zhang Zongying , Wang Nan , Chen Xuesen
Published: June 2021

Flavonoid content, which is an important indicator of the nutritional value of fruits and vegetables, directly determines the marketability of many fruit crops, including apple (Malus domestica). Brassinosteroids (BRs) are steroid hormones that affect flavonoid biosynthesis in plants, but the underlying regulatory mechanism remains unclear. In this study, treatments with brassinolide (the most active BR) and brassinazole (a BR biosynthesis inhibitor) decreased and increased, respectively, the flavonoid, anthocyanin, and proanthocyanidin (PA) content in red-fleshed apple seedlings and calli. We subsequently demonstrated that a BZR (BRI1-EMS-suppressor (BES)/brassinazole-resistant) family transcription factor, MdBEH2.2, participates in BR-regulated flavonoid biosynthesis. Specifically, MdBEH2.2 inhibits the accumulation of flavonoids, anthocyanins, and PAs in apple seedlings; however, brassinazole treatment weakens the inhibitory effect. Additionally, we confirmed that a BR-induced MYB TF, MdMYB60, interacts with MdBEH2.2. The resulting MdBEH2.2–MdMYB60 complex further enhances the inhibitory effect of MdBEH2.2 or MdMYB60 on the transcription of flavonoid biosynthesis-related genes. These results indicate that brassinolide decreases flavonoid content through the MdBEH2.2–MdMYB60 regulatory module. Our findings further clarify the molecular mechanism mediating the regulation of flavonoid biosynthesis by BR signals in horticultural crops.
Multiomics analysis of kernel development in response to short-term heat stress at the grain formation stage in waxy maize
Authors: Guo Jian , Gu Xiaotian , Lu Weiping , Lu Dalei
Published: June 2021

Understanding the adaptive changes in maize kernels under high-temperature stress during grain formation stage is critical for developing strategies to alleviate the negative effects on yield and quality. In this study, we subjected waxy maize (Zea mays L. sinensis Kulesh) to four different temperature regimes from 1–15 d after pollination (DAP), namely normal day/normal night (control), hot day/normal night, normal day/hot night, and hot day/hot night. Compared to the control, the three high-temperature treatments inhibited kernel development and starch deposition. To understand how the kernels responded to high-temperature stress, their transcriptomes, proteomes, and metabolomes were studied at 10 DAP and 25 DAP. This showed that genes and proteins related to kernel development and starch deposition were up- and down-regulated, respectively, at 10 DAP, but this pattern was reversed at 25 DAP. Metabolome profiling under high-temperature stress showed that the accumulation patterns of metabolites at 10 DAP and 25 DAP were inversely related. Our multiomics analyses indicated that the response to high-temperature stress of signaling pathways mediated by auxin, abscisic acid, and salicylic acid was more active at 10 DAP than at 25 DAP. These results confirmed that high-temperature stress during early kernel development has a carry-over effect on later development. Taken together, our multiomics profiles of developing kernels under high-temperature stress provide insights into the processes that underlie maize yield and quality under high-temperature conditions.
The CaM1-associated CCaMK–MKK1/6 cascade positively affects lateral root growth via auxin signaling under salt stress in rice
Authors: Yang Jun , Ji Lingxiao , Liu Shuang , Jing Pei , Hu Jin , Jin Deming , Wang Lingqiang , Xie Guosheng
Published: June 2021

Ca2+/calmodulin (CaM)-dependent protein kinases (CCaMKs) and mitogen-activated protein kinase kinases (MAPKKs) are two types of kinases that regulate salt stress response in plants. It remains unclear, however, how they cooperatively affect lateral root growth under salt stress. Here, two conserved phosphorylation sites (S102 and T118) of OsCaM1 were identified, and found to affect the ability to bind to Ca2+in vitro and the kinase activity of OsCCaMK in vivo. OsCCaMK specifically interacted with OsMKK1/6 in a Ca2+/CaM-dependent manner. In vitro kinase and in vivo dual-luciferase assays revealed that OsCCaMK phosphorylated OsMKK6 while OsMKK1 phosphorylated OsCCaMK. Overexpression and antisense-RNA repression expression of OsCaM1-1, and CRISPR/Cas9-mediated gene editing mutations of OsMKK1, OsMKK6, and OsMKK1/6 proved that OsCaM1-1, OsMKK1, and OsMKK6 enhanced the auxin content in roots and lateral root growth under salt stress. Consistently, OsCaM1-1, OsMKK1, and OsMKK6 regulated the transcript levels of the genes of this cascade, and salt stress-related and lateral root growth-related auxin signaling under salt stress in rice roots. These findings demonstrate that the OsCaM1-associated OsCCaMK–OsMKK1/6 cascade plays a critical role in recruiting auxin signaling in rice roots. These results also provide new insight into the regulatory mechanism of the CaM-mediated phosphorylation relay cascade to auxin signaling in lateral root growth under salt stress in plants.
Detailed characterization of the UMAMIT proteins provides insight into their evolution, amino acid transport properties, and role in the plant
Authors: Zhao Chengsong , Pratelli Réjane , Yu Shi , Shelley Brett , Collakova Eva , Pilot Guillaume
Published: June 2021

Amino acid transporters play a critical role in distributing amino acids within the cell compartments and between plant organs. Despite this importance, relatively few amino acid transporter genes have been characterized and their role elucidated with certainty. Two main families of proteins encode amino acid transporters in plants: the amino acid–polyamine–organocation superfamily, containing mostly importers, and the UMAMIT (usually multiple acids move in and out transporter) family, apparently encoding exporters, totaling 63 and 44 genes in Arabidopsis, respectively. Knowledge of UMAMITs is scarce, based on six Arabidopsis genes and a handful of genes from other species. To gain insight into the role of the members of this family and provide data to be used for future characterization, we studied the evolution of the UMAMITs in plants, and determined the functional properties, the structure, and localization of the 47 Arabidopsis UMAMITs. Our analysis showed that the AtUMAMITs are essentially localized at the tonoplast or the plasma membrane, and that most of them are able to export amino acids from the cytosol, confirming a role in intra- and intercellular amino acid transport. As an example, this set of data was used to hypothesize the role of a few AtUMAMITs in the plant and the cell.