bluuebunny/crossref_metadata_2025 huggingface dataset:
Actigraphy to Evaluate Changes in Physical Activity After Autologous Breast Reconstruction
Authors: Glassman Gabriella E. , Makhoul Alan T. , Zhang Michael , Johnson Shepard P. , Perdikis Galen , Drolet Brian C.
Published: January 2021

Purpose

Early ambulation and return to preoperative (baseline) ambulatory level is protective against postoperative venous thromboembolism. The duration of decreased physical activity after surgery is unknown for most procedures, as surgeons typically estimate physical recovery based on subjective patient reporting. This study aims to quantify the time it takes to return to baseline ambulatory status after breast reconstruction using actigraphy devices.

Methods

Actigraphy devices were used to evaluate preoperative and postoperative physical activity levels in patients undergoing autologous breast reconstruction at a single academic institution. Steps and resting heart rate (HR) were used as metrics of physical activity and physiological state. “Baseline” physical activity was defined by the average daily step count during the 14 days before surgery. “Return to baseline” occurred when the 7-day daily step average was greater than or equal to 95% of their baseline steps. Study participation was considered complete once a patient returned to baseline or surpassed 8 postoperative weeks.

Results

From May 2019 to April 2020, 17 patients were enrolled in the study before deep inferior epigastric perforator breast reconstruction. The mean age was 48.2 years and mean BMI was 27.6. This cohort averaged 7908 ± 3271 preoperative steps. Two patients returned to baseline activity by postoperative day 28. In total, 8 patients returned by postoperative week 8. Preoperative resting HR average was 73.5 ± 9.43 beats per minute. The average resting HR was elevated by 2.59%, 4.28%, and 2.31% at weeks 1, 2, and 3, respectively. The 7-day daily average resting HR had normalized by week 4.

Conclusions

Return to baseline physical activity after surgery may take longer than previously perceived, particularly after physiologically demanding surgeries, such as free flap breast reconstruction. These findings indicate that surgeons may underestimate the impact of surgery on physical decline and, consequently, may undertreat with venous thromboembolism prophylaxis.
An Assessment of Patient Satisfaction and Decisional Regret in Patients Undergoing Staged Free-Flap Breast Reconstruction
Authors: Shammas Ronnie L. , Sergesketter Amanda R. , Taskindoust Mahsa , Glener Adam D. , Cason Roger W. , Hollins Andrew , Atia Andrew N. , Mundy Lily R. , Hollenbeck Scott T.
Published: January 2021

Background

In the setting of radiation therapy or significant medical comorbidities, free-flap breast reconstruction may be intentionally delayed or staged with tissue expander placement (“delayed-immediate” approach). The effect of a staged approach on patient satisfaction and decisional regret remains unclear.

Methods

All patients undergoing free-flap breast reconstruction (n = 334) between 2014 and 2019 were identified. Complication rates, patient satisfaction using the BREAST-Q, and decisional regret using the Decision Regret Scale were compared between patients undergoing immediate, delayed, and staged approaches.

Results

Overall, 100 patients completed the BREAST-Q and Decision Regret Scale. BREAST-Q scores for psychosocial well-being (P = 0.19), sexual well-being (P = 0.26), satisfaction with breast (P = 0.28), physical well-being (chest, P = 0.49), and physical well-being (abdomen, P = 0.42) did not significantly vary between patients undergoing delayed, staged, or immediate reconstruction. Overall, patients experienced low regret after reconstruction (mean score, 11.5 ± 17.1), and there was no significant difference in regret scores by reconstruction timing (P = 0.09). Compared with normative BREAST-Q data, unlike immediate and delayed approaches, staged reconstruction was associated with lower sexual well-being (P = 0.006). Furthermore, a significantly higher infection rate was seen among staged patients (immediate 0%, delayed 5%, staged 20%, P = 0.01).

Conclusions

Staged free-flap breast reconstruction confers similar long-term satisfaction and decisional regret as immediate and delayed reconstruction but may be associated with worsened sexual well-being, when compared with normative data, and an increased risk of surgical site infection. When counseling patients regarding the timing of reconstruction, it is important to weigh these risks in the context of equivalent long-term satisfaction and decisional regret between immediate, delayed, and staged approaches.
Ischemic Complications After Bilateral Nipple-sparing Mastectomy and Implant-based Reconstruction
Authors: Razavi S. Amir , Hart Alexandra L. , Carlson Grant W.
Published: January 2021

Purpose

Nipple-sparing mastectomy (NSM) has a higher incidence of mastectomy skin flap necrosis (MSFN) than skin-sparing mastectomy. The purpose of this study is to analyze predisposing factors for nipple and skin necrosis after bilateral NSM with immediate implant reconstruction.

Methods

Sixty-two consecutive patients (124 breasts) from a single breast/plastic surgeon underwent bilateral NSM with immediate implant-based breast reconstruction were included. Factors influencing MSFN were analyzed.

Results

The mean age was 45.7 years, and mean body mass index was 22.9. Reconstructive methods were as follows: tissue expander (TE), 76 (61.3%); and direct to implant, 48 (38.7%). Mastectomy skin flap necrosis occurred in 39 (31.5%) breasts, nipple necrosis 38 and skin flap necrosis 19. Thirty-seven breasts healed uneventfully, and 2 (1.6%) required reoperation. Cancer pathology, mastectomy weight greater than 279 g, TE reconstruction, and nipple-notch (N-N) distance greater than 23 cm were predictive of nipple necrosis on univariate analysis. The mean mastectomy weight (380.1 g vs 220.7 g, P < 0.0001), N-N distance greater than 23 cm (30 vs 0, P < 0.0001), and mean implant size (490 cm3 vs 373 cm3, P < 0.0001) were greater in the TE group. On logistic regression model controlling for all significant variables, predictors of MSFN were as follows: diagnosis of cancer (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.41–8.03; P = 0.006), TE reconstruction (OR, 2.87; 95% CI, 1.03–8.03; P = 0.04), and N-N distance (OR, 1.31; 95% CI, 1.03–1.66; P = 0.03).

Conclusions

Mastectomy skin flap necrosis after NSM and implant reconstruction is common. In this series, only 2 (1.6%) cases required surgical intervention with no implant loss. Treatment of breast cancer, TE reconstruction, and increasing N-N notch distance were positive predictors of MSFN.
Managing Vascular Anomalies in the Era of Genetics and Precision Medicine
Authors: Gu Hao , Liu Hongyuan , Cai Ren , Chen Hui , Lin Xiaoxi
Published: January 2021

The era of genetics and precision medicine has been reforming this world. How will plastic surgeons in the field of vascular anomalies conform to the trend? This article systematically reviews the identification of serum biomarkers, risk factors, specific mutations in the angiogenesis-related genes such as GNAQ, RASA1, TEK, and their impact on the diagnosis and treatment of vascular anomalies with preliminary results that have been previously reported and leading the tide. Moreover, a new disease classification for complex vascular malformations based on PIK3CA genetic evidence and various treatment breakthroughs is briefly summarized. With gene sequencing, bioinformatics, and big data, we confront the challenges of research in the vascular anomalies domain and explore possibilities of precision medicine development.
Latent Safety Threats and Countermeasures in the Operating Theater
Authors: Long Jennifer A. , Webster Craig S. , Holliday Timothy , Torrie Jane , Weller Jennifer M.
Published: January 2021

Introduction

In situ simulation provides a valuable opportunity to identify latent safety threats (LSTs) in real clinical environments. Using a national simulation program, we explored latent safety threats (LSTs) identified during in situ multidisciplinary simulation-based training in operating theaters in hospitals across New Zealand.

Method

Surgical simulations lasting between 15 and 45 minutes each were run as part of a team training course delivered in 21 hospitals in New Zealand. After surgical in situ simulations, instructors used a template to record identified LSTs in a postcourse report. We analyzed these reports using the contributory factors framework from the London Protocol to categorize LSTs.

Results

Of 103 postcourse reports across 21 hospitals, 77 contained LSTs ranging across all factors in the London Protocol. Common threats included staff knowledge and skills in emergencies, team factors, factors related to task or technology, and work environment threats. Team factors were also commonly reported as protecting against adverse events, in particular, creating a shared mental model. Examples of actions taken to address threats included replacing or repairing faulty equipment, clarifying emergency processes, correcting written information, and staff training for clinical emergencies.

Conclusions

The pervasiveness of LSTs suggests that our results have widespread relevance to surgical departments throughout New Zealand and elsewhere and that collective solutions would be valuable. In situ simulation is an effective mechanism both for identifying threats to patient safety and to prompt initiatives for improvement, supporting the use of in situ simulation in the quality improvement cycle in healthcare.
A Tribute to Chad Epps
Authors: Palaganas Janice C. , Levine Adam I. , Manos Jennifer , Maxworthy Juli , Park Christine S. , Phrampus Paul , Peterson Dawn Taylor , Watts Penni I. , Young Jarrod , Cheng Adam
Published: January 2021

Summary Statement

Dr Chad Epps' journey in healthcare simulation touched countless lives in his role as a mentor, educator, leader, collaborator, and friend. Here, we highlight Chad's lasting impact upon which we all stand today.
Intravenous Local Anesthetic Compared With Intraperitoneal Local Anesthetic in Laparoscopic Colectomy
Authors: MacFater Wiremu S. , Xia Weisi , Barazanchi Ahmed W. H. , Lightfoot Nicholas J. , Weston Maree , Svirskis Darren , Hill Andrew G.
Published: January 2021

Introduction:

Controlling perioperative pain is essential to improving patient experience and satisfaction following surgery. Traditionally opioids have been frequently utilized for postoperative analgesia. Although they are effective at controlling pain, they are associated with adverse effects, including postoperative nausea, vomiting, ileus, and long-term opioid dependency.

Following laparoscopic colectomy, the use of intravenous or intraperitoneal infusions of lidocaine (IVL, IPL) are promising emerging analgesic options. Although both techniques are promising, there have been no direct, prospective randomized comparisons in patients undergoing laparoscopic colon resection. The purpose of this study was to compare IPL with IVL.

Methods:

Double-blinded, randomized controlled trial of patients undergoing laparoscopic colonic resection. The 2 groups received equal doses of either IPL or IVL which commenced intra-operatively with a bolus followed by a continuous infusion for 3 days postoperatively. Patients were cared for through a standardized enhanced recovery after surgery program. The primary outcome was total postoperative opioid consumption over the first 3 postoperative days. Patients were followed for 60 days.

Results:

Fifty-six patients were randomized in a 1:1 fashion to the IVL or IPL groups. Total opioid consumption over the first 3 postoperative days was significantly lower in the IPL group (70.9 mg vs 157.8 mg P < 0.05) and overall opioid consumption during the total length of stay was also significantly lower (80.3 mg vs 187.36 mg P < 0.05. Pain scores were significantly lower at 2 hours postoperatively in the IPL group, however, all other time points were not significant. There were no differences in complications between the 2 groups.

Conclusion:

Perioperative use of IPL results in a significant reduction in opioid consumption following laparoscopic colon surgery when compared to IVL. This suggests that the peritoneal cavity/compartment is a strategic target for local anesthetic administration. Future enhanced recovery after surgery recommendations should consider IPL as an important component of a multimodal pain strategy following colectomy.
Comparison of massive and emergency transfusion prediction scoring systems after trauma with a new Bleeding Risk Index score applied in-flight
Authors: Yang Shiming , Mackenzie Colin F. , Rock Peter , Lin Chienyu , Floccare Doug , Scalea Thomas , Stumpf Florian , Winans Christopher , Galvagno Samuel , Miller Catriona , Stein Deborah , Hu Peter F.
Published: January 2021

BACKGROUND

Assessment of blood consumption (ABC), shock index (SI), and Revised Trauma Score (RTS) are used to estimate the need for blood transfusion and triage. We compared Bleeding Risk Index (BRI) score calculated with trauma patient noninvasive vital signs and hypothesized that prehospital BRI has better performance compared with ABC, RTS, and SI for predicting the need for emergent and massive transfusion (MT).

METHODS

We analyzed 2-year in-flight data from adult trauma patients transported directly to a Level I trauma center via helicopter. The BRI scores 0 to 1 were derived from continuous features of photoplethymographic and electrocardiographic waveforms, oximetry values, blood pressure trends. The ABC, RTS, and SI were calculated using admission data. The area under the receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) was calculated for predictions of critical administration threshold (CAT, ≥3 units of blood in the first hour) or MT (≥10 units of blood in the first 24 hours). DeLong’s method was used to compare AUROCs for different scoring systems. p < 0.05 was considered statistically significant.

RESULTS

Among 1,396 patients, age was 46.5 ± 20.1 years (SD), 67.1% were male. The MT rate was 3.2% and CAT was 7.6%, most (92.8%) were blunt injury. Mortality was 6.6%. Scene arrival to hospital time was 35.3 ± (10.5) minutes. The BRI prediction of MT with AUROC 0.92 (95% CI, 0.89–0.95) was significantly better than ABC, SI, or RTS (AUROCs = 0.80, 0.83, 0.78, respectively; 95% CIs 0.73–0.87, 0.76–0.90, 0.71–0.85, respectively). The BRI prediction of CAT had an AUROC of 0.91 (95% CI, 0.86–0.94), which was significantly better than ABC (AUROC, 077; 95% CI, 0.73–0.82) or RTS (AUROC, 0.79; 95% CI, 0.74–0.83) and better than SI (AUROC, 0.85; 95% CI, 0.80–0.89). The BRI score threshold for optimal prediction of CAT was 0.25 and for MT was 0.28.

CONCLUSION

The autonomous continuous noninvasive patient vital signs–based BRI score performs better than ABC, RTS, and SI predictions of MT and CAT. Bleeding Risk Index does not require additional data entry or expert interpretation.

LEVEL OF EVIDENCE

Prognostic test, level III.
Diagnostic accuracy of prehospital triage tools for identifying major trauma in elderly injured patients: A systematic review
Authors: Fuller Gordon , Pandor Abdullah , Essat Munira , Sabir Lisa , Buckley-Woods Helen , Chatha Hridesh , Holt Chris , Keating Samuel , Turner Janette
Published: January 2021

BACKGROUND

Older adults with major trauma are frequently undertriaged, increasing the risk of preventable morbidity and mortality. The aim of this systematic review was to evaluate the diagnostic performance of prehospital triage tools to identify suspected elderly trauma patients in need of specialized trauma care.

METHODS

Several electronic databases (including MEDLINE, EMBASE, and the Cochrane Library) were searched from inception to February 2019. Prospective or retrospective diagnostic studies were eligible if they examined prehospital triage tools as index tests (either scored theoretically using observed patient variables or evaluated according to actual paramedic transport decisions) compared with a reference standard for major trauma in elderly adults who require transport by paramedics following injury. Selection of studies, data extraction, and risk of bias assessments using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool were undertaken independently by at least two reviewers. Narrative synthesis was used to summarize the findings.

RESULTS

Fifteen studies met the inclusion criteria, with 11 studies examining theoretical accuracy, three evaluating real-life transport decisions, and one assessing both (of 21 individual index tests). Estimates for sensitivity and specificity were highly variable with sensitivity estimates ranging from 19.8% to 95.5% and 57.7% to 83.3% for theoretical accuracy and real life triage performance, respectively. Specificity results were similarly diverse ranging from 17.0% to 93.1% for theoretical accuracy and 46.3% to 78.9% for actual paramedic decisions. Most studies had unclear or high risk of bias and applicability concerns. There were no obvious differences between different triage tools, and findings did not appear to vary systematically with major trauma prevalence, age, alternative reference standards, study designs, or setting.

CONCLUSION

Existing prehospital triage tools may not accurately identify elderly patients with serious injury. Future work should focus on more relevant reference standards, establishing the best trade-off between undertriage and overtriage, optimizing the role prehospital clinician judgment, and further developing geriatric specific triage variables and thresholds.

LEVEL OF EVIDENCE

Systematic review, level III.
Empowering the affected: Informing community-based solutions through interviews with survivors of interpersonal firearm violence—Perspectives of survivors of firearm injuries
Authors: Halimeh Bachar N. , Hughes Dorothy , Evans Blake , Emberson Julia , Turco Lauren , Zakrison Tanya L. , Winfield Robert D.
Published: January 2021

BACKGROUND

Firearm violence remains epidemic in the United States, with interpersonal gun violence leading to significant morbidity and mortality. Interpersonal violence has strong associations with social determinants of health, and community-specific solutions are needed to address root causes. We hypothesized that open-ended interviews with survivors of interpersonal firearm violence would identify themes in individual and community-level factors that contribute to ongoing violence.

METHODS

Between July 2017 and November 2019, we performed a mixed-methods study in which qualitative and quantitative data were obtained from survivors of interpersonal firearm violence admitted to our urban level I trauma center. Qualitative data were obtained through semistructured, open-ended interviews with survivors. Quantitative data were obtained via survey responses provided to these same individuals. Qualitative and quantitative data were then used to triangulate and strengthen results.

RESULTS

During the study period, 51 survivors were enrolled in the study. The most common cause of firearm violence reported by survivors was increased gang and drug activity (n = 40, 78%). The most common solution expressed was to reduce drug and gang lifestyle by offering jobs and educational opportunities to afflicted communities to improve opportunities (n = 35, 69%). Nearly half of the survivors (n = 23, 45%) believe that firearm violence should be dealt with by the affected community itself, and another group of survivors believe that it should be through partnership between the community and trauma centers (n = 19, 37%).

CONCLUSION

Interviews with survivors of firearm violence at our urban level I trauma center suggest that drug and gang lifestyle perpetuate ongoing violence and that this would best be overcome by improving access to quality education and job opportunities. To address endemic firearm violence in their communities, trauma centers should identify opportunities to partner in developing programs that provide improved education, job access, and conflict mediation.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level I.
Update on the management of status epilepticus
Authors: Rossetti Andrea O. , Alvarez Vincent
Published: January 2021

Purpose of review

Randomized controlled trials investigating the initial pharmacological treatment of status epilepticus have been recently published. Furthermore, status epilepticus arising in comatose survivors after cardiac arrest has received increasing attention in the last years. This review offers an updated assessment of status epilepticus treatment in these different scenarios.

Recent findings

Initial benzodiazepines underdosing is common and correlates with development of status epilepticus refractoriness. The recently published ESETT trial provides high-level evidence regarding the equivalence of fosphenytoin, valproate, and levetiracetam as a second-line option. Myoclonus or epileptiform transients on electroencephalography occur in up to 1/3 of patients surviving a cardiac arrest. Contrary to previous assumptions regarding an almost invariable association with death, at least 1/10 of them may awaken with reasonably good prognosis, if treated. Multimodal prognostication including clinical examination, EEG, somatosensory evoked potentials, biochemical markers, and neuroimaging help identifying patients with a chance to recover consciousness, in whom a trial with antimyoclonic compounds and at times general anesthetics is indicated.

There is a continuous, albeit relatively slow progress in knowledge regarding different aspect of status epilepticus; recent findings refine some treatment strategies and help improving patients’ outcomes. Further high-quality studies are clearly needed to further improve the management of these patients, especially those with severe, refractory status epilepticus forms.
Intrinsic dialogues between the two hemispheres in middle-aged male alcoholics: a resting-state functional MRI study
Authors: Dai Xiyong , Zhang Jianlong , Gao Lei , Yu Jinming , Li Yuanchun , Du Baoguo , Huang Xiangyi , Zhang Haibo
Published: January 2021

Background

The purpose of this study was to investigate the interhemispheric intrinsic connectivity measured by resting-state functional MRI (R-fMRI) in middle-aged male alcoholics.

Methods

Thirty male alcoholics (47.33 ± 8.30 years) and 30 healthy males (47.20 ± 6.17 years) were recruited and obtained R-fMRI data. Inter- and intrahemispheric coordination was performed by using voxel-mirrored homotopic connectivity (VMHC) and seed-based functional connectivity analysis.

Results

We found significantly decreased VMHC in a set of regions in male alcoholics patients, including lateral temporal, inferior frontal gyrus, insular/insulae operculum, precuneus/posterior cingulate gyrus, and pars triangularis (P < 0.05, corrected). Subsequent seed-based functional connectivity analysis demonstrated disrupted functional connectivity between the regions of local homotopic connectivity deficits and other areas of the brain, particularly the areas subserving the default, salience, primary somatomotor, and language systems.

Conclusions

Middle-aged male alcoholic subjects demonstrated prominent reductions in inter- and intrahemispheric functional coherence. These abnormal changes may reflect degeneration of system/network integration, particularly the domains subserving default, linguistic processing, and salience integration.
Ac-FLTD-CMK inhibits pyroptosis and exerts neuroprotective effect in a mice model of traumatic brain injury
Authors: Wang Pengfei , Pan Baogen , Tian Jun , Yang Lei , Chen Zeshang , Yang Lijun , Fan Zhenzeng
Published: January 2021

Pyroptosis has been reported to contribute to the traumatic brain injury (TBI) process. Ac-FLTD-CMK is a newly synthesized pyroptosis inhibitor. However, whether Ac-FLTD-CMK inhibits pyroptosis and plays a neuroprotective role after TBI is unknown. The present study aimed to determine the effects of Ac-FLTD-CMK on TBI in a mouse model. Male C57BL/6 mice were randomly divided into sham, TBI + vehicle, and TBI + Ac-FLTD-CMK groups. TBI was induced using a weight-drop apparatus. Intraventricular injection of Ac-FLTD-CMK was performed 30 min after TBI. Caspase-1, caspase-11, gasdermin-D (GSDMD), and caspase-3 expression in the peri-contusional cortex were assessed by western blotting. Interleukin-1β (IL-1β) and interleukin-18 (IL-18) expression in the peri-contusional cortex were measured using ELISA. Behavioral experiments, brain water content, Evans blue extravasation, lactate dehydrogenase (LDH) release, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining were also performed. The results showed that Ac-FLTD-CMK administration significantly downregulated caspase-1 p20, caspase-11 p20, GSDMD N-terminal, IL-1β, and IL-18 expression; reduced LDH release; alleviated neuronal death; attenuated brain edema and blood-brain barrier damage; and improved neurobehavioral function. These findings indicate that Ac-FLTD-CMK treatment suppresses pyroptosis and protects mice against TBI.
Pinoresinol diglucoside attenuates neuroinflammation, apoptosis and oxidative stress in a mice model with Alzheimer’s disease
Authors: Lei Shuangyuan , Wu Suli , Wang Guanzhuo , Li Bing , Liu Bin , Lei Xia
Published: January 2021

For Alzheimer’s disease (AD), there is still no effective treatment strategy. Pinoresinol diglucoside (PDG) is one of the major lignans isolated from Eucommia ulmoides. It is endowed with multiple pharmacological activities, including anti-inflammatory, antioxidant and anticancer activities. In this study, we investigated the potential neuroprotective functions of PDG in AD. Mice model with AD was established adopting stereotactic hippocampal injection of Aβ1-42 (410 pmol/mouse), and 3 days later, mice were administrated with 5 and 10 mg/kg PDG by intragastric administration every day for 3 weeks. Morris water maze and Y-maze tests demonstrated that PDG treatment could markedly reverse Aβ1-42-induced memory impairment in mice. It is found that PDG restrained the release of proinflammatory cytokines (tumor necrosis factor α and interleukin 1β), reactive oxygen species and malondialdehyde, and promoted the activity of the antioxidant enzyme (superoxide dismutase and catalase) by quantitative real-time-PCR, colorimetric method and ELISA assay. Western blot assay results have shown that PDG could also upregulate the ratio of Bcl-2/Bax and downregulate cytochrome c and cleaved caspase-3 expressions, thereby inhibiting neuronal apoptosis. Furthermore, PDG also significantly reduced the expression of Toll-like receptor 4 (TLR4) and the activation of nuclear factor-κB (NF-κB) p65, and promoted nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expressions. In conclusion, PDG can attenuate neuroinflammation, neuronal apoptosis and oxidative stress through the TLR4/NF-κB and Nrf2/HO-1 pathways, and ameliorate memory dysfunction induced by Aβ1-42 in mice.
Neural correlates of episodic memory change in increasing age: a longitudinal event-related potential study
Authors: Guerrero Lina F. , Bouazzaoui Badiâa , Isingrini Michel , Alibran Emilie , Angel Lucie
Published: January 2021

Using a longitudinal design, we examined whether event-related brain potentials (ERPs) correlates of successful episodic memory retrieval varied over a 4-year period according to the level of memory change. ERPs were recorded while participants performed a word-stem cued-recall task, and this procedure was repeated 4 years later. We compared the ERP old/new effect patterns of participants whose memory performance remained stable over time (stable group) with those of participants experiencing episodic memory decline (decline group). The pattern of change of the old/new effect differed between groups. At T1, the two groups exhibited the same pattern, with a positive frontal and parietal old/new effect. For the decline group, the old/new effect pattern did not change between T1 and T2. By contrast, for the stable group, the positive parietal old/new effect at T1 no longer appeared at T2, but a negative old/new effect was exhibited at frontal sites. This brain reorganization pattern could be a compensatory mechanism supporting strategic processes and allowing memory abilities to be maintained over time.
Expression of fibroblast growth factor 9 and its receptors in the dentate gyrus of hippocampus in poststroke depression rats
Authors: Li Aiping , Tian Jing , Yang Jianwen , Ren Xiang , Zhou Zhiwen , Zhou Wensheng
Published: January 2021

Studies have found that fibroblast growth factor 9 (FGF9) might have a negative effect in the psychiatric diseases, such as depression or anxiety, but its potential role in the pathophysiology of poststroke depression (PSD) remains uncertain. Here, we set out to investigate the expression changes of FGF9 and its receptors in PSD rats. Middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress was used to establish the PSD rat model. Then, the rats were randomly divided into four groups: control (sham-operation), MCAO, PSD and treated (fluoxetine injection by intraperitoneal). Weight measurement, sucrose preference test, open-field test and forced swim test were performed to evaluate the behavioral changes, and then Western blot and real-time quantitative PCR were used to detect the expression level of FGF9, fibroblast growth factor receptor 1 (FGFR1) and receptor 3 (FGFR3) in the dentate gyrus of rat hippocampus. We found that FGF9 protein and mRNA expression increased significantly in the MCAO and PSD groups; FGFR3 protein and mRNA expression decreased significantly in the MCAO and PSD groups; FGFR1 protein and mRNA expression decreased significantly in the PSD group, but increased in the treated group. Furthermore, the changes mentioned above were reversed obviously by fluoxetine. These results indicated that upregulated FGF9 expression and downregulated FGFR1 and FGFR3 expression may be involved in the pathogenesis of PSD, and the FGF9/FGFR signaling pathway may be considered as an attractive target for further study.
Evaluation of the hippocampal immunoreactivity of the serotonin 5-HT1A, 5-HT2 and 5-HT7 receptors in a pilocarpine temporal lobe epilepsy rat model with fast ripples
Authors: Núñez-Ochoa Miguel A. , Chiprés-Tinajero Gustavo A. , Medina-Ceja Laura
Published: January 2021

Fast ripples (FRs) are found in the hippocampus of epileptic brains, and this fast electrical activity has been described as a biomarker of the epileptogenic process itself. Results from our laboratory, such as the observation of decreased seizure rates and FR incidence at a specific citalopram dose, have suggested that serotonin (5-HT) may play a key role in the FR generation process. Therefore, to gather more details about the state of the serotoninergic system in the hippocampus under an epileptogenic process, we studied the immunoreactivity of three 5-HT receptors (5-HT1A, 5-HT2 and 5-HT7) as well as the extracellular levels of 5-HT in the hippocampal tissue of epileptic rats with FR. Wistar rats (210–300 g) were injected with a single dose of pilocarpine hydrochloride (2.4 mg/2 µl) in the right lateral ventricle and video-monitored 24 h/d to detect spontaneous and recurrent seizures; microelectrodes were implanted in the dentate gyrus (DG) and CA3 and CA1 regions of these rats ipsilateral to the pilocarpine injection site 1 day after the first spontaneous seizure was observed, and only rats who suffered FR events were used in this work. Thirty-three days after the first spontaneous seizure, an immunostaining procedure and high performance liquid chromatography were performed to measure the 5-HT levels. A general depletion of the 5-HT and 5-HIIA levels in hippocampal tissue from epileptic animals compared with those in controls was observed; in addition, a general decrease in immunoreactivity for the three receptors was found, especially in the DG, which may support the establishment of an excitatory/inhibitory imbalance in the trisynaptic circuit that underlies the FR generation process.
Salivary markers and coronavirus disease 2019: insights from cross-talk between the oral microbiome and pulmonary and systemic low-grade inflammation and implications for vascular complications
Authors: AbdelMassih Antoine , Hassan Alaa A. , Abou-Zeid Aya S. , Hassan Aya , Hussein Engy , Gadalla Mahenar , Hussein Mahinour , Eid Maryam A. , Elahmady Maryam , El Nahhas Nadine , Emad Nadine , Zahra Nihal , Aboushadi Nour , Ibrahim Nourhan , Mokhtar Sherouk , Ismail Habiba-Allah , El-Husseiny Nadine , Moharam Reham Khaled , Menshawey Esraa , Menshawey Rahma
Published: January 2021

To date, coronavirus disease 2019 (COVID-19) has affected over 6.2 million individuals worldwide, including 1.46 million deaths. COVID-19 complications are mainly induced by low-grade inflammation-causing vascular degeneration. There is an increasing body of evidence that suggests that oral dysbiotic taxa are associated with worse prognosis in COVID-19 patients, especially the Prevotella genus, which was retrieved from nasopharyngeal and bronchoalveolar lavage samples in affected patients. Oral dysbiosis may act by increasing the likelihood of vascular complications through low-grade inflammation, as well as impairing respiratory mucosal barrier mechanisms against SARS-CoV-2. Salivary markers can be used to reflect this oral dysbiosis and its subsequent damaging effects on and the lungs and vasculature. Salivary sampling can be self-collected, and is less costly and less invasive, and thus may be a superior option to serum markers in risk stratification of COVID-19 patients. Prospective studies are needed to confirm such hypothesis.

Video Abstract: http://links.lww.com/CAEN/A28
Prognostic significance of BMI after PCI treatment in ST-elevation myocardial infarction A cohort study from the Swedish Coronary Angiography and Angioplasty Registry
Authors: Jamaly Shabbar , Redfors Björn , Omerovic Elmir , Carlsson Lena , Karason Kristjan
Published: January 2021

Background

Obesity along with clustering of cardiovascular risk factors is a promoter for coronary artery disease. On the other hand, a high BMI appears to exert a protective effect with respect to outcomes after a coronary artery event, termed the obesity paradox.

Methods

The Swedish Coronary and Angiography and Angioplasty registry (SCAAR) collects information on all patients who undergo percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in Sweden along with demographic- and procedure-related data. We studied the predictability of four categories of BMI for 1-year all-cause mortality in people with STEMI undergoing PCI.

Results

Among 25,384 patients, mean (SD) age 67.7 (12.1) years and 71.1% male, who underwent PCI for STEMI a total of 5,529 (21.8%) died within one year. Using normal-weight (BMI 18.5-24.9 kg/m2) as a reference, subjects with obesity (BMI ≥30 kg/m2) had a low 1-year all-cause mortality risk in unadjusted analysis, HR 0.59 (95% CI 0.53– 0.67). However, after adjustment for age, sex and other covariates the difference became non-significant, HR 0.88 (95% CI: 0.75-1.02). Patients with overweight (BMI 25.0-29.9 kg/m2) had the lowest 1-year mortality risk in analysis adjusted for age, sex and other covariates, HR 0.87 (95% CI 0.79-0.95), whereas those with underweight (BMI <18.5 kg/m2) had the highest mortality in both unadjusted HR 2.22 (95% CI 1.69–2.92) and adjusted analysis, HR 1.72 (95% CI: 1.31-2.26).

Conclusion

The protective effect of obesity with respect to 1-year mortality after coronary intervention became non-significant after adjusting for age, sex and relevant co-variates. Instead, overweight people displayed the lowest risk and underweight individuals the highest risk for adjusted all-cause mortality
Hidden Parameters Impacting Resurgence of SARS-CoV-2 Pandemic*
Authors: Zhang Yi , Kapoor Sanjiv
Published: January 2021

The spread of the COVID-19 virus has had an enormous impact on the world’s health and socioeconomic system. While lockdowns, which severely limit the movement of the population, have been implemented in March 2020 and again recently, the psychological and economic cost are severe. Removal of these restrictions occurred with varying degrees of success.

To study the resurgence of the virus in some communities we consider an epidemiological model, SIR-SD-L, that incorporates introduction of new population due to the removal of lockdown and identify parameters that impact the spread of the virus. This compartmental model of the epidemic incorporates a social distance metric based on progression of the infections; it models the dynamic propensity of infection spread based on the current infections relative to the susceptible population. The model is validated using data on growth of infections, hospitalizations and death, considering 24 counties in multiple US states and a categorization of the lockdown removal policies after the first lockdown. Model parameters, which include a compartment for the isolated population, are used to determine the rate at which the susceptible population increases to fit the rate of infections. Along with social distancing mandates, we identify active infections and the susceptible population as important factors in the resurgence of infections. We measure the efficacy of the lockdown removal policy via a ratio, PIR, which evaluates to less than 1 for counties where social distancing measures were mandated and which delayed complete re-opening of closed spaces like bars and restaurants. For other counties this ratio is greater than 1.

We also studied infection growth in the 24 US counties with respect to a release policy derived from CDC guidelines and compared against strategies that delay the removal of lockdown.

Our results illustrate that guidelines for deciding when lockdown rules are to be relaxed should consider the current state of the infectious population and the remaining susceptible population, hidden parameters that are deducible from models such as SIR-SD-L, and not limit policy considerations to the rate of new infections alone. This is especially true for counties where the growth rate of the virus is initially slow and misleading. Emphasis on social distancing is critical.
Factors associated with deaths due to COVID-19 versus other causes: population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform
Authors: Bhaskaran K , Bacon SCJ , Evans SJW , Bates CJ , Rentsch CT , MacKenna B , Tomlinson L , Walker AJ , Schultze A , Morton CE , Grint D , Mehrkar A , Eggo RM , Inglesby P , Douglas IJ , McDonald HI , Cockburn J , Williamson EJ , Evans D , Curtis HJ , Hulme WJ , Parry J , Hester F , Harper S , Spiegelhalter D , Smeeth L , Goldacre B
Published: January 2021

Background

Mortality from COVID-19 shows a strong relationship with age and pre-existing medical conditions, as does mortality from other causes. However it is unclear how specific factors are differentially associated with COVID-19 mortality as compared to mortality from other causes.

Methods

Working on behalf of NHS England, we carried out a cohort study within the OpenSAFELY platform. Primary care data from England were linked to national death registrations. We included all adults (aged ≥18 years) in the database on 1st February 2020 and with >1 year of continuous prior registration, the cut-off date for deaths was 9th November 2020. Associations between individual-level characteristics and COVID-19 and non-COVID deaths were estimated by fitting age- and sex-adjusted logistic models for these two outcomes.

Results

17,456,515 individuals were included. 17,063 died from COVID-19 and 134,316 from other causes. Most factors associated with COVID-19 death were similarly associated with non-COVID death, but the magnitudes of association differed. Older age was more strongly associated with COVID-19 death than non-COVID death (e.g. ORs 40.7 [95% CI 37.7-43.8] and 29.6 [28.9-30.3] respectively for ≥80 vs 50-59 years), as was male sex, deprivation, obesity, and some comorbidities. Smoking, history of cancer and chronic liver disease had stronger associations with non-COVID than COVID-19 death. All non-white ethnic groups had higher odds than white of COVID-19 death (OR for Black: 2.20 [1.96-2.47], South Asian: 2.33 [2.16-2.52]), but lower odds than white of non-COVID death (Black: 0.88 [0.83-0.94], South Asian: 0.78 [0.75-0.81]).

Interpretation

Similar associations of most individual-level factors with COVID-19 and non-COVID death suggest that COVID-19 largely multiplies existing risks faced by patients, with some notable exceptions. Identifying the unique factors contributing to the excess COVID-19 mortality risk among non-white groups is a priority to inform efforts to reduce deaths from COVID-19.

Funding

Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.
Estimating the effects of non-pharmaceutical interventions on the number of new infections with COVID-19 during the first epidemic wave
Authors: Banholzer Nicolas , van Weenen Eva , Lison Adrian , Cenedese Alberto , Seeliger Arne , Kratzwald Bernhard , Tschernutter Daniel , Salles Joan Puig , Bottrighi Pierluigi , Lehtinen Sonja , Feuerriegel Stefan , Vach Werner
Published: January 2021

The novel coronavirus (SARS-CoV-2) has rapidly developed into a global epidemic. To control its spread, countries have implemented non-pharmaceutical interventions (NPIs), such as school closures, gathering bans, or even stay-at-home orders. Here we study the effectiveness of seven NPIs in reducing the number of new infections, which was inferred from the reported cases of COVID-19 using a semi-mechanistic Bayesian hierarchical model. Based on data from the first epidemic wave ofn= 20 countries (i.e., the United States, Canada, Australia, the EU-15 countries, Norway, and Switzerland), we estimate the relative reduction in the number of new infections attributed to each NPI. Among the NPIs considered, event bans were most effective, followed by venue and school closures, whereas stay-at-home orders and work bans were least effective. With this retrospective cross-country analysis, we provide estimates regarding the effectiveness of different NPIs during the first epidemic wave.
Sensitivity of Estimated Tacrolimus Population Pharmacokinetic Profile to Inaccurate Assumptions about Dose Timing and Absorption: An Investigation in Real-World and Simulated Data
Authors: Williams Michael L. , Weeks Hannah L. , Beck Cole , Choi Leena
Published: January 2021

A population pharmacokinetic (PK) study with 363 subjects was performed using real-world data extracted from electronic heath records (EHRs) to estimate the tacrolimus population PK profile. As population PK studies for oral medications performed using EHR data often assume a regular dosing schedule as prescribed without incorporating exact dosing time, we assessed the sensitivity of the PK parameter estimates to assumptions about dose timing using last-dose times extracted by our own natural language processing system, medExtractR. We also investigated the sensitivity of estimations to absorption rate constants that are often fixed at a published value in tacrolimus population PK analysis. There was no appreciable difference in parameters estimates with vs. without last-dose time incorporated in the data and our sensitivity analysis revealed little difference between parameters estimated assuming a range of absorption rate constants. We also conducted simulation studies to investigate how drug PK profiles and experimental designs such as concentration measurements affects sensitivity to incorrect assumptions about dose timing and absorption rates. Our findings suggest that drugs with a slower elimination rate (or a longer half-life) are less sensitive to dose timing errors and that experimental designs which only allow for trough blood concentrations are usually insensitive to deviation in absorption rate.
The impact of Spike mutations on SARS-CoV-2 neutralization
Authors: Rees-Spear C , Muir L , Griffith SA , Heaney J , Aldon Y , Snitselaar JL , Thomas P , Graham C , Seow J , Lee N , Rosa A , Roustan C , Houlihan CF , Sanders RW , Gupta R , Cherepanov P , Stauss H , Nastouli E , Doores KJ , van Gils MJ , McCoy LE
Published: January 2021

Multiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike. Antibodies from SARS-CoV-2 infection neutralize the virus by focused targeting of Spike and there is limited serum cross-neutralization of the closely-related SARS-CoV. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, 501Y.V2 and P.1 lineages, it is critical to understand if antibody responses induced by infection with the original SARS-CoV-2 virus or the current vaccines will remain effective against virus variants. In this study we evaluate neutralization of a series of mutated Spike pseudotypes including a B.1.1.7 Spike pseudotype. The analyses of a panel of Spike-specific monoclonal antibodies revealed that the neutralizing activity of some antibodies was dramatically reduced by Spike mutations. In contrast, polyclonal antibodies in the serum of patients infected in early 2020 remained active against most mutated Spike pseudotypes. The majority of serum samples were equally able to neutralize the B.1.1.7 Spike pseudotype, however potency was reduced in a small number of samples (3 of 36) by 5–10-fold. This work highlights that changes in the SARS-CoV-2 Spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.
Saccades along spatial neural circuit discontinuities
Authors: Malevich Tatiana , Hafed Ziad M.
Published: January 2021

Saccades are realized by six extraocular muscles that define the final reference frame for eyeball rotations. However, upstream of the nuclei innervating the eye muscles, eye movement commands are represented in two-dimensional retinocentric coordinates, as is the case in the superior colliculus (SC). In such spatial coordinates, the horizontal and vertical visual field meridians, relative to the line of sight, are associated with neural tissue discontinuities due to routing of binocular retinal outputs when forming retinotopic sensory-motor maps. At the level of the SC, a functional discontinuity along the horizontal meridian was additionally discovered, beyond the structural vertical discontinuity associated with hemifield lateralization. How do such neural circuit discontinuities influence purely cardinal saccades? Using thousands of saccades from 3 rhesus macaque monkeys and 14 human subjects, we show how the likelihood of purely horizontal or vertical saccades is infinitesimally small, nulling a discontinuity problem. This does not mean that saccades are sloppy. On the contrary, saccades exhibit remarkable direction and amplitude corrections to account for small initial eye position deviations due to fixational variability: “purely” cardinal saccades can deviate, with an orthogonal component of as little as 0.03 deg, to correct for tiny target position deviations from initial eye position. In humans, probing perceptual target localization additionally revealed that saccades show different biases from perception when targets deviate slightly from purely cardinal directions. These results demonstrate a new functional role for fixational eye movements in visually-guided behavior, and they motivate further neurophysiological investigations of saccade trajectory control in the brainstem.

New and Noteworthy

Purely cardinal saccades are often characterized as being straight. We show how a small amount of curvature is inevitable, alleviating an implementational problem of dealing with neural circuit discontinuities in the representations of the visual meridians. The small curvature functionally corrects for minute variability in initial eye position due to fixational eye movements. Saccades are far from sloppy; they deviate by as little as <1% of the total vector size to adjust their landing position.