bluuebunny/crossref_metadata_2025 huggingface dataset:
Mental Health During COVID-19 Lockdown in the United Kingdom
Authors: Pieh Christoph , Budimir Sanja , Delgadillo Jaime , Barkham Michael , Fontaine Johnny R. J. , Probst Thomas
Published: October 2020

Objective

The coronavirus disease (COVID-19) pandemic and related lockdown measures have raised important questions about the impact on mental health. This study evaluated several mental health and well-being indicators in a large sample from the United Kingdom (UK) during the COVID-19 lockdown where the death rate is currently among the highest in Europe.

Methods

A cross-sectional online survey with a study sample that mirrors general population norms according to sex, age, education, and region was launched 4 weeks after lockdown measures were implemented in the UK. Measures included mental health–related quality of life (World Health Organization Quality-of-Life Brief Version psychological domain), well-being (World Health Organization Well-Being Index), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), perceived stress (Perceived Stress Scale-10), and insomnia (Insomnia Severity Index). Analyses of variances, Bonferroni-corrected post hoc tests, and t tests were applied to examine mental health indicators across different sociodemographic groups (age, sex, employment, income, physical activity, relationship status).

Results

The sample comprised n = 1006 respondents (54% women) from all regions of the UK. Approximately 52% of respondents screened positive for a common mental disorder, and 28% screened positive for clinical insomnia. Mean scores and standard deviations were as follows: Patient Health Questionnaire-9, mean = 9.0 ± 7.7; Generalized Anxiety Disorder-7, mean = 8.0 ± 6.5; Insomnia Severity Index, mean = 10.4 ± 7.0; Perceived Stress Scale-10, mean = 17.7 ± 7.9; World Health Organization Quality-of-Life Brief Version, mean = 58.6 ± 21.4; and World Health Organization Well-Being Index score, mean = 13.0 ± 6.0. Statistical analyses consistently indicated more severe mental health problems in adults younger than 35 years, women, people with no work, and people with low income (all p values < .05). Mental health indices also varied across UK regions.

Conclusions

The prevalence of depressive, anxiety, and insomnia symptoms is significantly higher in the UK relative to prepandemic epidemiological data. Further studies are needed to clarify the causes for these high rates of mental health symptoms.
Postoperative Abdominal Bulge and Hernia Rates in Patients Undergoing Abdominally Based Autologous Breast Reconstruction
Authors: Espinosa-de-los-Monteros Antonio , Frias-Frias Roberto , Alvarez-Tostado-Rivera Alejandro , Caralampio-Castro Ali , Llanes Sergio , Saldivar Alberto
Published: October 2020

Bulge and hernia may occur after abdominally based breast reconstruction. The purpose of this study is to provide an estimate of the effects that the type of flap used for breast reconstruction (ie, transverse rectus abdominis muscle [TRAM] vs muscle-sparing [MS]-2 TRAM vs DIEP) has on the postoperative development of both abdominal bulge and abdominal hernia, taking into consideration the method of donor site closure (ie, with mesh vs without mesh), based on the available literature. Twenty-eight studies met the inclusion criteria and were included in the systematic review. From these, 9 studies were comparative and suitable for meta-analysis. The results showed that, for unilateral breast reconstructions, there was no statistically significant difference in hernia/bulge rates in the following techniques: MS-2 TRAM flap without mesh, MS-2 TRAM flap with mesh, and DIEP flap without mesh, and they showed significantly lower hernia/bulge rates compared with TRAM flap without mesh, and TRAM flap with mesh, whereas for bilateral reconstructions, there was no statistically significant difference in hernia/bulge rates in the following techniques: MS-2 TRAM flaps with mesh and DIEP flaps without mesh, and they showed significantly lower hernia/bulge rates compared with TRAM flaps without mesh, TRAM flaps with mesh, and MS-2 TRAM flaps without mesh.
New Chimeric Groin Flap
Authors: Morarasu Stefan , Ghetu Nicolae , Coman Corneliu George , Boicu Daniel , Spiridon Irene Alexandra , Gardikiotis Ioannis , Danciu Mihai , Pieptu Dragos
Published: October 2020

Aim

Increased emphasis is on using tissue substitutes and stem cells to improve flap applicability and survival rates. To accomplish this, the first step is to have a versatile experimental flap, easy to harvest and use as a template. We sought to develop a reliable experimental chimeric groin flap with free mobility and reliable bloods supply that can be twisted, relocated, and integrated easily with other materials.

Materials and Methods

Ten male Wistar rats were included. The flap consists of a 2.5-cm skin paddle centered on the medial branch of the inferior epigastric artery and a 4.5/2-cm fat pad supplied by the lateral branch of the inferior epigastric artery. After being raised, flaps were resutured in their anatomical position. Flaps were followed up for 15 days. At the end of the study, the viability of flaps was analyzed by ultrahigh-frequency ultrasound, nontargeted contrast study, and histology assessment.

Results

All flaps survived without significant complications. Nontargeted microbubbles spread evenly in both the superficial and deep flap. Ultrasound assessment at day 15 showed no significant areas of necrosis or edema. Histology examination of 3 random flaps confirmed vessel patency and flap viability.

Conclusion

We propose a simple, easy to harvest and reliable experimental flap which offers a main advantage of all-around mobility through its chimeric design. It is a suitable model for bioengineering studies as it can be used as a template for integration of tissue substitutes or stem cells, between its 2 components.
Free Vascularized Fibula Flap Reconstruction of Total and Near-total Destabilizing Resections of the Sacrum
Authors: Asaad Malke , Mericli Alexander F. , Hanasono Matthew M. , Roubaud Margaret S. , Bird Justin E. , Rhines Laurence D.
Published: October 2020

Background

Vascularized bone grafts (VBGs) are associated with improved union and fewer instrumentation complications in the mobile spine. It is not known if VBGs are similarly efficacious after sacrectomy.

Methods

We conducted a retrospective chart review of all patients who underwent total sacrectomy and immediate reconstruction with VBG between 2005 and 2019. Patient and surgical characteristics in addition to union and functional outcomes were analyzed.

Results

We identified 10 patients (6 women and 4 men) with a mean age of 42 years (range, 12–71 years). All patients received iliolumbar instrumentation as well as a free fibula flap as a VBG. There were no complications at the fibula flap donor site or specifically related to the VBG. Bony union was achieved in 7 (88%) of 8 patients with an average union time of 6.3 months (range, 2–10 months). Surgical complications occurred in 5 patients, 4 patients required reoperation for wound dehiscence, and 1 patient required conversion to a 4-rod construct and bone grafting for instrumentation loosening and partial nonunion. Instrumentation failure developed in 1 patient, but no surgical intervention was required. One patient was able to walk independently without any limitation, 5 patients required a walker, 2 were wheelchair-bound except for short (<15 ft) distances, and 2 were lost to follow-up.

Conclusions

The free vascularized fibula flap is a safe and effective option for supplementing spinal reconstruction after destabilizing sacrectomy.
The Hybrid Latissimus Dorsi Flap in Immediate Breast Reconstruction
Authors: Lee Hyung Chul , Lee Jaemin , Park Seung-Ha , Yoon Eul-Sik
Published: October 2020

Purpose

The implant-enhanced latissimus dorsi (LD) flap, or a hybrid LD flap, is widely used in certain indications, even though abdominal-based flaps are now considered the gold standard of autologous breast reconstruction. However, few articles distinguish the hybrid LD flap from traditional LD flaps, and not many articles have compared the surgical outcomes, with the abdominal-based flap procedure, especially in the area of immediate breast reconstruction. In addition, it is often overlooked that the reported esthetic comparisons are based on different populations and contralateral balancing procedures (CBPs). Thus, this study aimed to review the reconstruction outcomes and to compare the variable-matched esthetic outcomes between 2 groups.

Methods

A retrospective review of patients who underwent immediate breast reconstruction with either a hybrid LD flap or an abdominal-based free flap and had completed at least 2 years of follow-up visits was carried out. The patient demographics, oncologic data, breast parameters, and postoperative outcomes were compared across the entire patient group. The body mass index (BMI)- and CBP-matched cohort was randomly selected and assessed using the Aesthetic Outcome parameter of the Aesthetic Item Scale.

Result

Thirty-eight hybrid LD flap and 51 abdominal-based free flap procedures were included. The hybrid LD group showed a shorter operation time (330 ± 260 minutes vs 550 ± 480 minutes, respectively; P < 0.01), and fewer patients in the hybrid LD group underwent additional revision surgeries (7 [18.4%] vs 20 [39.2%], respectively; P < 0.01). Other complication rates were not significantly different between groups. A BMI- and CBP-matched esthetic analysis revealed that the hybrid LD group showed superior results in symmetry (Mann-Whitney U test, P = 0.047).

Conclusions

The LD flap in combination with an implant remains a viable option in immediate breast reconstruction and had a similar complication profile while having a shorter operative time compared with the abdominal-based autologous breast reconstruction procedure. If properly used in certain populations, hybrid LD flaps may offer superior results regarding symmetry over the abdominal-based flap procedure.
Clinical and Financial Implications of Positive Margins After Nonmelanoma Skin Cancer Resection
Authors: Ranganath Bharat , Teixeira Robert M. , Patel Tyag , Garza Ramon , Murphy Robert X.
Published: October 2020

Background

Management of positive margins after nonmelanoma skin cancer (NMSC) excision is debated in the literature. The purpose of this study is to determine the rate of residual tumor in reexcised NMSC specimens after previous excision with positive margins, to determine the rate of recurrence in patients who had positive margins but did not undergo reexcision, and to define the financial burden of negative reexcisions.

Methods

An Institutional Review Board-approved retrospective review was conducted on all patients with NMSC excision over a 15-year period. Patients who met inclusion criteria and underwent initial NMSC excision with negative frozen section margins, but had positive permanent section margins were divided into 2 groups: those who underwent reexcision for clearance of tumor (n = 161) or those who did not undergo further reexcision (n = 105). Variables collected include demographics, previous skin cancer, tumor location, cancer subtype, excision measurements, and time between first and second excisions. For those patients who did not undergo reexcision, charts were examined for recurrence.

Results

Two hundred sixty-six patients met inclusion criteria with mean follow-up of 60 months. Eighty-three (52%) of 161 patients with positive margins on initial excision had no evidence of residual cancer upon reexcision. Residual tumor on permanent section was confirmed in 48% of patients. Patients with a previous history of basal cell carcinoma were more likely to have a true-positive margin after reexcision (P = 0.02). Larger reexcisions were more likely to harbor residual cancer (5.9 cm2, P = 0.04). Patients with positive margins that did not undergo reexcision, only 7 of 105 patients (6.6%) had recurrence. No mortalities were reported from NMSC recurrence. US $247,672 was spent in reexcision for negative margins in 98 patients for an average cost of US $2984 per case.

Conclusions

Forty-eight percent of NMSC patients with positive margins had residual tumor upon reexcision. There were 6.6% of the patients who did not undergo resection after positive margins developed recurrence of disease at 5 years. Patients requiring larger reexcisions or those with a prior history of BCC were more likely to have residual cancer upon reexcision. This study suggests that observation is an appropriate option of care for certain patients with residual NMSC on permanent pathology.
Depression predicts long-term cognitive impairment in survivors of critical illness
Authors: Nordness Mina Faye , Bipin Patel Mayur , Erickson Caroline R. , Kiehl Amy , Jackson James C. , Raman Rameela , Pandharipande Pratik P. , Ely E. Wesley , Wilson Jo Ellen
Published: October 2020

INTRODUCTION

Intensive care unit (ICU) survivorship is associated with long-term cognitive impairment (LTCI). Our work has found post-ICU depression in up to 30% and posttraumatic stress disorder (PTSD) in up to 10% of ICU survivors. We hypothesized that post-ICU depression and PTSD are independently associated with LTCI in ICU survivors.

METHODS

This is a five-center nested prospective cohort of critically ill patients admitted to medical and surgical ICUs who underwent neuropsychological assessments at 3 and 12 months posthospital discharge. Our primary outcome was global cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Trail Making Test, Part B, a test of executive functioning, at 3- and 12-month follow-up. Our independent variables were Beck Depression Inventory II and the PTSD Checklist—Specific Version measured at 3 and 12 months. We performed multivariable linear regression models controlling for covariates such as age, years of education, preexisting cognitive impairment, comorbidities, ventilator days, hypoxemia episodes, and days of delirium or coma.

RESULTS

Of 1,047 patients in the combined cohort, 679 were alive and available for follow-up at 3 months. A total of 590 (87%) ICU survivors completed at least one 3-month assessment, and of the 554 who survived to 12 months, 519 (94%) completed both a 3- and 12-month assessment with a median age of 61 years (52–70 years) and mean daily Sequential Organ Failure Assessment score of 6 (4–8), 520 (88%) were mechanically ventilated, and 420 (71%) were with delirium. Of these, 113 (19%) had PTSD and 187 (32%) had depression at 3 months with similar rates at 12 months. Depression at 3 months was associated with lower 3-month RBANS (coefficient, −2.25; −3.10 to −1.39) and lower Trails B scores at both 3 months (odds ratio, 0.69; 0.56–0.85) and 12 months (odds ratio, 0.66; 0.52–0.84). Posttraumatic stress disorder at 3 months had no association with RBANS or Trails B scores at 3 or 12 months.

CONCLUSION

Early post-ICU depression, but not PTSD, is independently associated with coexisting LTCI, even when controlling for past ICU delirium. Treatment for early depression represents a novel intervention area for LTCI prevention in ICU survivors.

LEVEL OF EVIDENCE

Prognostic/epidemiological, level III.
Hard signs gone soft: A critical evaluation of presenting signs of extremity vascular injury
Authors: Romagnoli Anna Noel , DuBose Joseph , Dua Anahita , Betzold Richard , Bee Tiffany , Fabian Timothy , Morrison Jonathan , Skarupa David , Podbielski Jeanette , Inaba Kenji , Feliciano David , Kauvar David ,   AAST PROOVIT Study Group
Published: October 2020

BACKGROUND

Despite advances in management of extremity vascular injuries, “hard signs” remain the primary criterion to determine need for imaging and urgency of exploration. We propose that hard signs are outdated and that hemorrhagic and ischemic signs of vascular injury may be of greater clinical utility.

METHODS

Extremity arterial injuries from the American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment registry were analyzed to examine the relationships between hard signs, ischemic signs, and hemorrhagic signs of extremity vascular injury with workup, diagnosis, and management.

RESULTS

Of 1,910 cases, 1,108 (58%) had hard signs of vascular injury. Computed tomography angiography (CTA) was more commonly used as the diagnostic modality in patients without hard signs, while operative exploration was primarily used for diagnosis in hard signs. Patients undergoing CTA were more likely to undergo endovascular or hybrid repair (EHR) (10.7%) compared with patients who underwent exploration for diagnosis (1.5%). Of 915 patients presenting with hemorrhagic signs, CTA was performed 14.5% of the time and was associated with a higher rate of EHR and observation. Of the 490 patients presenting with ischemic signs, CTA was performed 31.6% of the time and was associated with higher rates of EHR and observation. Hemorrhagic signs were associated with arterial transection, while ischemic signs were associated with arterial occlusion. Patients with ischemic signs undergoing exploration for diagnosis received more units of packed red blood cells during the first 24 hours. There was no difference in amputation rate, reintervention rate, hospital length of stay, or mortality in comparing groups who underwent CTA versus exploration.

CONCLUSION

Hard signs have limitations in identification and characterization of extremity arterial injuries. A strategy of using hemorrhagic and ischemic signs of vascular injury is of greater clinical utility. Further prospective study is needed to validate this proposed redefinition of categorization of presentations of extremity arterial injury.

LEVEL OF EVIDENCE

Diagnostic, level III.
Does preoperative magnetic resonance imaging alter the surgical plan in patients with acute traumatic cervical spinal cord injury?
Authors: Buchanan Frank R. , Wang Vincent Y. , Amadio Jordan P. , Ortega-Barnett Juan R. , Brown Lawrence H. , Teixeira Pedro G. , Aydelotte Jayson D. , Leede Emily , Ali Sadia , Brown Carlos V.R.
Published: October 2020

BACKGROUND

Whether magnetic resonance imaging (MRI) adds value to surgical planning for patients with acute traumatic cervical spinal cord injury (ATCSCI) remains controversial. In this study, we compared surgeons' operative planning decisions with and without preoperative MRI. We had two hypotheses: (1) the surgical plan for ATCSCI would not change substantially after the MRI and (2) intersurgeon agreement on the surgical plan would also not change substantially after the MRI.

METHODS

We performed a vignette-based survey study that included a retrospective review of all adult trauma patients who presented to our American College of Surgeons-verified level 1 trauma center from 2010 to 2019 with signs of acute quadriplegia and underwent computed tomography (CT), MRI, and subsequent cervical spine surgery within 48 hours of admission. We abstracted patient demographics, admission physiology, and injury details. Patient clinical scenarios were presented to three spine surgeons, first with only the CT and then, a minimum of 2 weeks later, with both the CT and MRI. At each presentation, the surgeons identified their surgical plan, which included timing (none, <8, <24, >24 hours), approach (anterior, posterior, circumferential), and targeted vertebral levels. The outcomes were change in surgical plan and intersurgeon agreement. We used Fleiss' kappa (κ) to measure intersurgeon agreement.

RESULTS

Twenty-nine patients met the criteria and were included. Ninety-three percent of the surgical plans were changed after the MRI. Intersurgeon agreement was “slight” to “fair” both before the MRI (timing, κ = 0.22; approach, κ = 0.35; levels, κ = 0.13) and after the MRI (timing, κ = 0.06; approach, κ = 0.27; levels, κ = 0.10).

CONCLUSION

Surgical plans for ATCSCI changed substantially when the MRI was presented in addition to the CT; however, intersurgeon agreement regarding the surgical plan was low and not improved by the addition of the MRI.

LEVEL OF EVIDENCE

Diagnostic, level II.
Prognostic value of CT perfusion and permeability imaging in traumatic brain injury
Authors: Avsenik Jernej , Bajrović Fajko F. , Gradišek Primož , Kejžar Nataša , Šurlan Popović Katarina
Published: October 2020

BACKGROUND

Currently established prognostic models in traumatic brain injury (TBI) include noncontrast computed tomography (CT) which is insensitive to early perfusion alterations associated with secondary brain injury. Perfusion CT (PCT) on the other hand offers insight into early perfusion abnormalities. We hypothesized that adding CT perfusion and permeability data to the established outcome predictors improves the performance of the prognostic model.

METHODS

A prospective cohort study of consecutive 50 adult patients with head injury and Glasgow Coma Scale score of 12 or less was performed at a single Level 1 Trauma Centre. Perfusion CT was added to routine control CT 12 hours to 24 hours after admission. Region of interest analysis was performed in six major vascular territories on perfusion and permeability parametric maps. Glasgow Outcome Scale (GOS) was used 6 months later to categorize patients’ functional outcomes to favorable (GOS score > 3) or unfavorable (GOS score ≤ 3). We defined core prognostic model, consisting of age, motor Glasgow Coma Scale score, pupillary reactivity, and CT Rotterdam Score. Next, we added perfusion and permeability data as predictors and compared updated models to the core model using cross-validated areas under the receiver operator curves (cv-AUC).

RESULTS

Significant advantage over core model was shown by the model, containing both mean cerebral extravascular-extracellular volume per unit of tissue volume and cerebral blood volume of the least perfused arterial territory in addition to core predictors (cv-AUC, 0.75; 95% confidence interval, 0.51–0.84 vs. 0.6; 95% confidence interval, 0.37–0.74).

CONCLUSION

The development of cerebral ischemia and traumatic cerebral edema constitutes the secondary brain injury and represents the target for therapeutic interventions. Our results suggest that adding CT perfusion and permeability data to the established outcome predictors improves the performance of the prognostic model in the setting of moderate and severe TBI.

LEVEL OF EVIDENCE

Prognostic study, level III.
Dementia Incidence in the Elderly Population of Greece
Authors: Vlachos George S. , Kosmidis Mary H. , Yannakoulia Mary , Dardiotis Efthimios , Hadjigeorgiou Georgios , Tzoulaki Ioanna , Georgiou Andrea N. , Sakka Paraskevi , Anastasiou Costas A. , Stefanis Leonidas , Scarmeas Nikolaos
Published: October 2020

Objectives:

Recently a declining trend in dementia incidence rates has been reported in high-income countries. We investigated dementia incidence in a representative sample of the Greek population in the age group of 65 years and above.

Methods:

This research is part of the Hellenic Epidemiological Longitudinal Investigation of Aging and Diet (HELIAD). The incidence cohort consisted of 1072 participants who were reevaluated after a mean period of 3.09 years.

Results:

The incidence rate of dementia was 19.0 cases per 1000 person-years (age-standardized and sex-standardized incidence: 25.4/1000 person-years), of which 16.3 per 1000 person-years were attributable to Alzheimer disease. Each additional year of age increased dementia risk by 19.3% and each additional year of education decreased dementia risk by 12.1%. Apolipoprotein E (APOE)-ε4 homozygous participants were 18 times more likely to be diagnosed with dementia. A baseline diagnosis of mild cognitive decline (MCI) resulted in a risk for dementia increased by 3.7 times compared with the cognitively normal; in participants with MCI at baseline, APOE-ε4 carriage increased dementia risk by 4.5 times.

Conclusions:

The incidence rate of dementia in people 65 years and above in Greece is generally consistent with recently published rates in Europe and North America. Advancing age, baseline MCI, and APOE-ε4 homozygosity are risk factors, while higher educational attainment seems protective.
Biomarker Use for Dementia With Lewy Body Diagnosis
Authors: Armstrong Melissa J. , Irwin David J. , Leverenz James B. , Gamez Noheli , Taylor Angela , Galvin James E.
Published: October 2020

Background:

Dementia with Lewy body (DLB) diagnostic criteria define “indicative” and “supportive” biomarkers, but clinical practice patterns are unknown.

Methods:

An anonymous survey querying clinical use of diagnostic tests/biomarkers was sent to 38 center of excellence investigators. The survey included “indicative” biomarkers (dopamine transporter scan, myocardial scintigraphy, polysomnography), “supportive” biomarkers [magnetic resonance imaging (MRI)], positron emission tomography, or single-photon emission computed tomography perfusion/metabolism scans, quantitative electroencephalography), and other diagnostic tests (neuropsychological testing, cerebrospinal fluid analysis, genetics). Responses were analyzed descriptively.

Results:

Of the 22 respondents (58%), all reported the capability to perform neuropsychological testing, MRI, polysomnography, dopamine transporter scans, positron emission tomography/single-photon emission computed tomography scans, and cerebrospinal fluid analysis; 96% could order genetic testing. Neuropsychological testing and MRI were the most commonly ordered tests. Diagnostic testing beyond MRI and neuropsychological testing was most helpful in the context of “possible” DLB and mild cognitive impairment and to assist with differential diagnosis. Myocardial scintigraphy and electroencephalograpy use were rare.

Conclusions and Relevance:

Neuropsychological testing and MRI remain the most widely used diagnostic tests by DLB specialists. Other tests—particularly indicative biomarkers—are used only selectively. Research is needed to validate existing potential DLB biomarkers, develop new biomarkers, and investigate mechanisms to improve DLB diagnosis.
Sex Moderates the Relationship of Stress and Perceived Social Support With Neuropsychological Symptoms Among Community-dwelling Persons With Alzheimer Disease in Spain
Authors: Gomez-Gallego María , Gallego-Mellado María , Gómez-Gallego Juan C. , Gómez-García Juan G.
Published: October 2020

Neuropsychiatric symptoms (NPS) are common in Alzheimer disease (AD) patients, especially in women. Stress and stress-vulnerability factors (eg, poor social support) may trigger NPS. This cross-sectional study (n=196) aimed to examine the moderating effect of sex on the relationships between both perceived social support and salivary cortisol levels and NPS of AD patients. Only in women, greater cortisol levels were associated with higher scores in Neuropsychiatric Inventory mood, agitation, and frontal subscales whereas higher Psychosocial Support Questionnaire scores were related to lower scores in Neuropsychiatric Inventory mood and psychosis subscales. Given the relevance that sex differences might have on the design of preventive strategies, present findings should be confirmed in longitudinal studies.
Value of Electroconvulsive Therapy in the General Public
Authors: Ulbrich Laura , Kröger Christoph
Published: October 2020

Objective

The aims of this study were to estimate the value a population-representative sample places on electroconvulsive therapy (ECT) through willingness to pay (WTP) and to assess the effects of individual characteristics on WTP for ECT.

Methods

A German population-representative sample of 518 was presented with a hypothetical health loss scenario of depression and was asked to indicate WTP for ECT. Probit and quantile regression were used to estimate the effects of individual characteristics on the probability of stating a positive WTP and on the amount of money respondents were willing to pay.

Results

Two thirds of respondents stated that they had no knowledge about ECT. Most (56.5%) respondents indicated zero WTP for health gains through ECT treatment. Mean WTP was €5201 ($5612); median WTP was €1000 ($1079). Respondents' monthly household income had a significant effect on the probability of stating a positive WTP. Assessing WTP above zero, income showed a significant positive effect, whereas a higher score of depressive complaints showed a significant negative effect on the amount respondents were willing to pay.

Conclusion

Knowledge about ECT treatment is particularly low in the German public.
Transcranial Direct Current Stimulation for Prader-Willi Syndrome
Authors: Azevedo Caroline C. , Trevizol Alisson Paulino , Gomes July S. , Akiba Henrique , Franco Ruth R. , Simurro Paula B. , Ianni Renata M. , Grigolon Ruth B. , Blumberger Daniel M. , Dias Alvaro M.
Published: October 2020

Background

Given the limited therapeutic options for Prader-Willi syndrome (PWS), we conducted an open-label clinical trial to evaluate the effects of transcranial direct current stimulation (tDCS) for hyperphagia, food craving, and aberrant behaviors on this population.

Methods

Twelve subjects with PWS (11–35 years old) were included. The subjects underwent 10 daily 20-minute sessions of tDCS in 2 weeks. The anode was positioned over the left dorsolateral prefrontal cortex, and the cathode over the contralateral region.

Results

We observed amelioration of hyperphagic and food craving symptoms (P < 0.05), as well as amelioration of behavioral symptoms measured with the Aberrant Behavior Checklist (P < 0.05).

Discussion

To our knowledge, this is the first proof-of-concept trial to report the positive effects of increasing excitability of the left dorsolateral prefrontal cortex, using tDCS, for the behavioral, hyperphagia, and food craving symptoms in PWS, which is a low-cost, well-studied, safe alternative for brain stimulation.
Vagus Nerve Stimulation in Patients Receiving Maintenance Therapy With Electroconvulsive Therapy
Authors: Aaronson Scott T. , Goldwaser Eric L. , Kutzer Dennis J. , McAllister-Williams R. Hamish , Sackeim Harold A. , Rush A. John
Published: October 2020

Objectives

Electroconvulsive therapy (ECT) is a mainstay in both acute and long-term management of difficult-to-treat depression. However, frequent acute courses of ECT or prolonged maintenance ECT treatment may increase adverse-effect burden and/or reduce patient acceptability. Therefore, we investigated the effectiveness of adjunctive vagus nerve stimulation (VNS) therapy as an alternative strategy for long-term maintenance treatment in ECT-responsive patients.

Methods

This retrospective chart review identified maintenance ECT patients with unipolar (n = 5) and bipolar depression (n = 5) from 2 large hospital systems who had a history of ECT response, but the patients had significant residual incapacitating symptoms or increasing concerns regarding the burden associated with ECT and opted to receive adjunctive VNS therapy. The patients were followed for 2 years after VNS implantation. Response and remission were defined as Clinical Global Impression—Severity scale scores of ≤2 and 1, respectively, obtained at 1- and 2-year postimplantation compared with just before VNS implantation.

Results

One-year postimplantation, 6 of 10 had responded of which 5 met remission criteria. All 10 patients benefited from adjunctive VNS therapy with either fewer hospitalizations and/or ECT sessions. Seven of 10 stopped maintenance ECT by the end of year 1; an additional patient stopped maintenance ECT by year 2. No patients required an acute course of ECT during the 2-year follow-up. There was a statistically significant reduction (P < 0.0001) in mean (SD) Clinical Global Impression—Severity scale scores between baseline (5.4 [0.51]) and the 1-year postimplantation (2.1 [1.37]) time points, and between baseline and the 2-year postimplantation (2.3 [1.16]) time points, whereas no difference existed between the 1- and 2-year postimplantation time points.

Conclusions

Vagus nerve stimulation therapy may be a useful maintenance strategy in patients with difficult-to-treat depression receiving maintenance ECT.
Malaria parasites differentially sense environmental elasticity during transmission
Authors: Ripp Johanna , Kehrer Jessica , Smyrnakou Xanthoula , Tisch Nathalie , de Almodovar Carmen Ruiz , Frischknecht Friedrich
Published: October 2020

Transmission of malaria-causing parasites to and by the mosquito rely on active parasite migration and constitute bottlenecks in thePlasmodiumlife cycle. Parasite adaption to the biochemically and physically different environments must hence be a key evolutionary driver for transmission efficiency. To probe how subtle but physiologically relevant changes in environmental elasticity impact parasite migration, we introduce 2D and 3D polyacrylamide gels to study ookinetes, the parasite forms emigrating from the mosquito blood meal and sporozoites, the forms transmitted to the vertebrate host. We show that ookinetes adapt their migratory path but not their speed to environmental elasticity and are motile for over 24 hours on soft substrates. In contrast, sporozoites evolved more short-lived rapid gliding motility for rapidly crossing the skin. Strikingly, sporozoites are highly sensitive to substrate elasticity possibly to avoid adhesion on soft endothelial cells on their long way to the liver. Hence the two migratory stages ofPlasmodiumevolved different strategies to overcome the physical challenges posed by the respective environments and barriers they encounter.

Highlights

Plasmodiumookinetes can move for over 24 hours on very soft substrates mimicking the blood meal

Plasmodiumookinetes change their migration path according to substrate stiffness

Plasmodiumsporozoites are highly sensitive to subtle changes in substrate elasticity

Sporozoite may have evolved to not attach to the soft endothelium to help reach the liver
Assessing the Functional Impact of PfRh5 Genetic Diversity on Ex vivo Erythrocyte Invasion Inhibition
Authors: Moore Adam J. , Mangou Khadidiatou , Diallo Fatoumata , Sene Seynabou D. , Pouye Mariama N. , Sadio Bacary D. , Faye Ousmane , Mbengue Alassane , Bei Amy K.
Published: October 2020

The PfRh5-Basigin ligand-receptor interaction is an essential step in the merozoite invasion process and represents an attractive vaccine target. To reveal genotype-phenotype associations between naturally occurring allelic variants of PfRh5 and invasion inhibition, we performed ex vivo invasion inhibition assays with monoclonal antibodies targeting basigin coupled with PfRh5 next-generation amplicon sequencing. We found dose-dependent inhibition of invasion across all isolates tested, and no statistically significant difference in invasion inhibition for any single nucleotide polymorphisms. This study demonstrates that PfRh5 remains highly conserved and functionally essential, even in a highly endemic setting, supporting continued development as a strain-transcendent malaria vaccine target.
In Vivo Mitochondrial ATP Production Is Improved in Older Adult Skeletal Muscle After a Single Dose of Elamipretide in a Randomized Trial
Authors: Roshanravan Baback , Liu Sophia Z. , Shankland Eric G. , Amory John K. , Robertson H. Thomas , Marcinek David J. , Conley Kevin E.
Published: October 2020

Background

Loss of mitochondrial function contributes to fatigue, exercise intolerance and muscle weakness, and is a key factor in the disability that develops with age and a wide variety of chronic disorders. Here, we describe the impact of a first-in-class cardiolipin-binding compound that is targeted to mitochondria and improves oxidative phosphorylation capacity (Elamipretide, ELAM) in a randomized, double-blind, placebo-controlled clinical trial.

Methods

Non-invasive magnetic resonance and optical spectroscopy provided measures of mitochondrial capacity (ATPmax) with exercise and mitochondrial coupling (ATP supply per O2 uptake; P/O) at rest. The first dorsal interosseous (FDI) muscle was studied in 39 healthy older adult subjects (60 to 85 yrs of age; 46% female) who were enrolled based on the presence of poorly functioning mitochondria. We measured volitional fatigue resistance by force-time integral over repetitive muscle contractions.

Results

A single ELAM dose elevated mitochondrial energetic capacity in vivo relative to placebo (ΔATPmax; P=0.055, %ΔATPmax; P=0.045) immediately after a 2-hour infusion. No difference was found on day 7 after treatment, which is consistent with the half-life of ELAM in human blood. No significant changes were found in resting muscle mitochondrial coupling. Despite the increase in ATPmax there was no significant effect of treatment on fatigue resistance in the FDI.

Conclusions

These results highlight that ELAM rapidly and reversibly elevates mitochondrial capacity after a single dose. This response represents the first demonstration of a pharmacological intervention that can reverse mitochondrial dysfunction in vivo immediately after treatment in aging human muscle.
A One-Minute Blood Test to Monitor Immune Responses in COVID-19 Patients and Predict Clinical Risks of Developing Moderate to Severe Symptoms
Authors: Deb Chirajyoti , Salinas Allan N. , Middleton Aurea , Kern Katelyn , Penoyer Daleen , Borsadia Rahul , Hunley Charles , Mehta Vijay , Irastorza Laura , Mehta Devendra I. , Zheng Tianyu , Huo Qun
Published: October 2020

Coronavirus disease 2019 (COVID-19) has brought enormous loss and interruption to human life and the global economy since the first outbreak reported in China between late 2019 to early 2020, and will likely remain a public health threat in the months and years to come. Upon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms, however, a small percentage of the population will become severely ill, require hospitalization, intensive care, and some succumb to death. The current knowledge of COVID-19 disease progression with worsening symptom complex implicates the critical importance of identifying patients with high clinical risk compared to those who would be at lower risk for disease control and patient management with better therapeutic output. Currently no clinical test is available that can predict risk factors and immune status change at different severity scales. The immune system plays a critical role in the defense against infectious diseases. Extensive research has found that COVID-19 patients with poor clinical outcomes differ significantly in their immune responses to the virus from those who exhibit milder symptoms. We previously developed a nanoparticle-enabled blood test that can detect the humoral immune status change in animals. In this study, we applied this new test to analyze the immune response in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected statistically significant differences between COVID-19 patients with no or mild symptoms from those who developed moderate to severe symptoms. Mechanistic study suggests that these differences are associated with type 1 versus type 2 immune responses. We conclude that this new rapid test could potentially become a valuable clinical tool for COVID-19 patient risk stratification and management.
Close contact infection dynamics over time: insights from a second large-scale social contact survey in Flanders, Belgium, in 2010-2011
Authors: Van Hoang Thang , Coletti Pietro , Kiffe Yimer Wasihun , Van Kerckhove Kim , Vercruysse Sarah , Willem Lander , Beutels Philippe , Hens Niel
Published: October 2020

Background

In 2010-2011, we conducted a social contact survey in Flanders, Belgium, aimed at improving and extending the design of the first social contact survey conducted in Belgium in 2006. This second social contact survey aimed to enable, for the first time, the estimation of social mixing patterns for an age range of 0 to 99 years and the investigation of whether contact rates remain stable over this 5-year time period.

Methods

Different data mining techniques are used to explore the data, and the age-specific number of social contacts and the age-specific contact rates are modelled using a GAMLSS model. We compare different matrices using assortativeness measures. The relative change in the basic reproduction number (R0) and the ratio of relative incidences with 95% bootstrap confidence intervals (BCI) are employed to investigate and quantify the impact on epidemic spread due to differences in gender, day of the week, holiday vs. regular periods and changes in mixing patterns over the 5-year time gap between the 2006 and 2010-2011 surveys. Finally, we compare the fit of the contact matrices in 2006 and 2010-2011 to Varicella serological data.

Results

All estimated contact patterns featured strong homophily in age and gender, especially for small children and adolescents. A 30% (95% BCI [17%; 37%] ) and 29% (95% BCI [14%; 40%] ) reduction in R0 was observed for weekend versus weekdays and for holiday versus regular periods, respectively. Significantly more interactions between people aged 60+ years and their grandchildren were observed on holiday and weekend days than on regular weekdays. Comparing contact patterns using different methods did not show any substantial differences over the 5-year time period under study.

Conclusions

The second social contact survey in Flanders, Belgium, endorses the findings of its 2006 predecessor and adds important information on the social mixing patterns of people older than 60 years of age. Based on this analysis, the mixing patterns of people older than 60 years exhibit considerable heterogeneity, and overall, the comparison of the two surveys shows that social contact rates can be assumed stable in Flanders over a time span of 5 years.
Epidemiological and clinical characteristics of COVID-19 in Brazil using digital technology
Authors: Hajar Faissal N. , Fernandes-Silva Miguel M. , Pereira da Cunha Gustavo S. , Hamud Ali B. , Herrera Geny H. , Azevedo Valderílio F.
Published: October 2020

Background

Brazil has the third-highest number of Coronavirus disease 2019 (COVID-19) cases worldwide. Understanding the epidemiology of COVID-19 from reported cases is challenging due to heterogeneous testing rates. We estimated the number of COVID-19 cases in Brazil on a national and regional level using digital technology.

Methods

We used a web-based application to perform a population-based survey from March 21st to August 29th, 2020 in Brazil. We obtained responses from 243 461 individuals across all federative units, who answered questions on COVID-19-related symptoms, chronic diseases and address of residence. COVID-19 was defined as at least one of the following: fever, cough, dyspnea and nasal flaring, associated with a history of close contact with a suspect or confirmed COVID-19 case in the previous 14 days. A stratified two-stage weighted survey analysis was performed to estimate the population level prevalence of COVID-19 cases.

Results

After calibration weighing, we estimated that 10 339 461 cases of COVID-19 occurred, yielding a 2.75 estimated infection per officially reported case. Estimated/reported ratios varied across Brazilian states and were higher in states with lower human development indexes. Areas with lower income levels displayed higher rates of COVID-19 cases (66 vs 38 cases/1000 people in the lowest and highest income strata respectively, p<0.001), but presented lower rates of COVID-19 testing.

Conclusion

In this population-based survey using digital technology in Brazil, we estimated that the COVID-19 case rates were 2.75 times higher than officially reported. The estimated per reported case ratios were higher in areas with worse socioeconomic status.
Tumor cell total mRNA expression shapes the molecular and clinical phenotype of cancer
Authors: Cao Shaolong , Wang Jennifer R. , Ji Shuangxi , Yang Peng , Montierth Matthew D. , Guo Shuai , Shen John Paul , Zhao Xiao , Chen Jingxiao , Lee Jaewon James , Guerrero Paola A , Spetsieris Nicholas , Engedal Nikolai , Taavitsainen Sinja , Yu Kaixian , Livingstone Julie , Bhandari Vinayak , Hubert Shawna M , Daw Najat C. , Futreal P. Andrew , Efstathiou Eleni , Lim Bora , Viale Andrea , Zhang Jianjun , Nykter Matti , Czerniak Bogdan A , Msaouel Pavlos , Maitra Anirban , Kopetz Scott , Campbell Peter , Speed Terence P. , Boutros Paul C. , Zhu Hongtu , Urbanucci Alfonso , Demeulemeester Jonas , Van Loo Peter , Wang Wenyi
Published: October 2020

Cancers can vary greatly in their transcriptomes. In contrast to alterations in specific genes or pathways, differences in tumor cell total mRNA content have not been comprehensively assessed. Technical and analytical challenges have impeded examination of total mRNA expression at scale across cancers. To address this, we developed a model for quantifying tumor-specific total mRNA expression (TmS) from bulk sequencing data, which performs transcriptomic deconvolution while adjusting for mixed genomes. We used single-cell RNA sequencing data to demonstrate total mRNA expression as a feature of tumor phenotype. We estimated and validated TmS in 5,015 patients across 15 cancer types identifying significant inter-individual variability. At a pan-cancer level, high TmS is associated with increased risk of disease progression and death. Cancer type-specific patterns of genetic alterations, intra-tumor genetic heterogeneity, as well as pan-cancer trends in metabolic dysregulation and hypoxia contribute to TmS. Taken together, our results suggest that measuring cell-type specific total mRNA expression offers a broader perspective of tracking cancer transcriptomes, which has important biological and clinical implications.
Automatic Measurement of Inner Ear in Different Mammals1
Authors: Du Yi , Qin Han-dai , Liu Chen , Liu Da , Yuan Shuo-long , Jiang Qing-qing , Yang Jun , Li Gang , Xie Hong-lan , Zhao Jian-guo , Yu Ning , Yang Shi-ming
Published: October 2020

Objective

The aim of this research is to develop an accurate and automatic measuring method based on the aid of centerline to construct three dimensional models of inner ear in different mammals and to assess the morphological variations.

Methods

Three adult healthy mice, three adult guinea pigs, three adult mini pigs and one left temporal bone of human were included in this research. All 18 animal specimens and the human sample were scanned with the use of Micro-CT. After being segmented, three-dimensional models of the inner ear in different mammals were reconstructed using Mimics. A novel method with the use of centerline was established to estimate the properties of 3D models and to calculate the length, volume and angle parameters automatically.

Results

Morphological models of inner ears in different mammals have been built, which describe detailed shape of cochlear, vestibule, semicircular canals and common crus. Mean value of lengths and volumes of the cochlear, lateral semicircular canal, superior semicircular canal and posterior semicircular canal, tended to increase with the body size of the mammals, showed the proximity to the human data in mini pig. The angles between the semicircular canal planes showed differences between mammals. The mean values of semicircular canals of mice and mini pigs closely resembled to human data in numerical assessment.

Conclusion

The automatic measurement of the inner ear based on centerline builds an effective way to assess lengths, volumes and angles of three-dimensional structures. This study provides a theoretical basis for mechanical analysis of inner ear in different mammals and proves the similarity between mini pig and human.