bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolated splenic metastasis of endometrial cancer 12 years after treatment
Authors: Teng Xiali , Jiang Min , Zhu Xiaowei , Dou Rongrong , Yuan Donglan , Huang Junxing , Yu Hong
Published: May 2022

Rationale:

The spleen is an uncommon metastatic organ for malignant solid tumors because of its special anatomy and microenvironment. Isolated splenic metastasis of endometrial cancer is an extremely rare clinical event, with only 17 cases reported in literature.

Patient concerns:

We report the case of a 58-year-old woman with abdominal distension and nausea for 7 months who had undergone surgery and chemotherapy for endometrioid adenocarcinoma 12 years previously. A space-occupying lesion in the upper pole of the spleen was observed on an abdominal ultrasound.

Diagnosis:

The spleen was resected, and splenic metastasis of endometrial adenocarcinoma was histologically confirmed.

Interventions:

Splenectomy was performed, and no lymph nodes or other metastases were observed. The patient received postoperative chemotherapy with 6 cycles of docetaxel and carboplatin.

Outcomes:

The patient recovered well 11 months postoperatively, with no evidence of recurrence or metastatic disease.

Lesson:

Since the time interval between the diagnosis of primary endometrial cancer and splenic metastasis may be very long, it may be necessary to monitor the recurrence of endometrial cancer after primary treatment.
Predictive value of postoperative serum prealbumin levels for early detection of anastomotic leak after esophagectomy
Authors: Huang Jin , Tian Lei , Wang Bin
Published: May 2022

The impact of serum prealbumin in patients with esophageal carcinoma after undergoing esophagectomy remains unclear, we speculated that serum prealbumin is associated with anastomotic leak (AL) after surgery, low serum prealbumin level may lead to AL. The aim of the study was to evaluate the relationship between serum prealbumin levels and AL after esophagectomy, to explore the value of serum prealbumin as an early predictor of AL after esophagectomy.

Between January 2014 and December 2018, 255 patients were enrolled in this study, their basic characteristics and perioperative serum prealbumin levels were retrospectively analyzed. Statistical analysis by t test, nonparametric test and logistic regression were used to analyze data for patients with and without AL. Based on a receiver operator characteristic curve, a cut-off value for serum prealbumin levels as a predictor of AL was determined.

Among the 255 patients, 18 patients were diagnosed with AL. The overall AL rate was 7.0% (18/255) including 12 cases of intrathoracic AL and 6 cases of cervical AL. By univariate analysis, we identified postoperative serum prealbumin level as a risk factor for AL (P < .001). Multivariate analysis also demonstrated postoperative serum prealbumin level (P = .028) to be an independent risk factor for AL. The best cut-off value of postoperative serum prealbumin level was 131 mg/L for predicting AL, with 83.3% sensitivity and 72.2% specificity.

Postoperative serum prealbumin level was significantly associated with AL. it may help the early prediction of postoperative AL.
Using Interprofessional Simulation with Telehealth to Enhance Teamwork and Communication in Home Care
Authors: Keiser Megan M. , Turkelson Carman , Smith Leslie M. , Yorke Amy M.
Published: May 2022

Interpersonal communication and teamwork are critical to patient safety. There is evidence supporting the effectiveness of formalized team training strategies such as simulation-based learning experiences to permit opportunities for deliberate practice and skill acquisition. However, there is a paucity of evidence examining the best method for delivery of simulation-based interprofessional education activities (Sim-IPE). The purpose of this project was to explore the effectiveness of using a Sim-IPE with a home-based patient assessment and intervention for students in undergraduate nursing, nurse practitioner, and physical therapy programs with the goal of enhancing interprofessional team communication and team performance. A mixed-methods, observational research design was used to evaluate teamwork and communication following virtual/web-based deliberate practice and a subsequent face-to-face Sim-IPE with telehealth. There were two distinct stages: (1) provision of interprofessional education elements of teamwork and communication via a virtual web-based platform to interprofessional student teams; (2) participation of all 29 student teams in a Sim-IPE activity using a standardized patient in a simulated home-based setting. Teams scored very high on an interprofessional communication and teamwork scale, and students strongly agreed that the prebriefing, scenario, and debriefing assisted in their learning. Students also valued exposure to telehealth and the ability to work with students from other health professions.
Preventing Falls and Fall-Related Injuries at Home
Authors: Powell-Cope Gail , Thomason Susan , Bulat Tatjana , Pippins Karla M. , Young Heather M.
Published: May 2022

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home.

The articles in this new installment of the series explain principles for promoting safe mobility that nurses should reinforce with family caregivers. Each article also includes an informational tear sheet—Information for Family Caregivers—that contains links to instructional videos. To use this series, nurses should read the article first, so they understand how best to help family caregivers, and then encourage the caregivers to watch the videos and ask questions. For additional information, see Resources for Nurses.
A Multilevel Approach to Investigate Relationships Between Healthcare Resources and Lung Cancer
Authors: Somayaji Darryl , Seo Young S. , Wilding Gregory E. , Noyes Ekaterina
Published: May 2022

Background

Screening for lung cancer is an evidence-based but underutilized measure to reduce the burden of lung cancer mortality. Lack of adequate data on geographic availability of lung cancer screening inhibits the ability of healthcare providers to help patients with decision-making and impedes equity-focused implementation of screening-supportive services.

Objectives

This analysis used data from the 2012–2016 Surveillance, Epidemiology, and End Results (SEER) Program, the Behavioral Risk Factor Surveillance System, and the county health ranking to examine (a) which cancer resources and county-level factors are associated with late-stage lung cancer at diagnosis and (b) associations between county rurality and lung cancer incidence/mortality rates.

Methods

Using the New York state SEER data, we identified 68,990 lung cancer patients aged 20–112 years; 48.3% had late-stage lung cancers, and the average lung cancer incidence and mortality rates were 70.7 and 46.2 per 100,000, respectively. There were 144 American College of Radiology-designated lung cancer screening centers and 376 Federally Qualified Health Centers identified in New York state. County rurality was associated with a higher proportion of late-stage lung cancers and higher lung cancer mortality rates.

Discussion

Visual geomapping showed the scarcity of rural counties’ healthcare resources. County rurality is a significant factor in differences in lung cancer screening resources and patient outcomes. Use of publicly available data with geospatial methods provides ways to identify areas for improvement, populations at risk, and additional infrastructure needs.
Epstein-Barr Virus-positive Mucocutanous Ulcer of the Uterine Cervix: Report of a Rare and Evolving Entity
Authors: Razack Rubina , Cariem Rabia , Irusen Semira , Mohosho Mokoena , de Jager Louis
Published: May 2022

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a newly described lymphoproliferative lesion characterized by the proliferation of EBV-positive atypical B cells in a variable inflammatory background associated with mucosal or cutaneous ulcers. Commonly involved sites include the oropharyngeal tract, skin, and gastrointestinal tract, with emerging reports describing EBVMCU of genitalia. To date, no lesions have been described of the uterine cervix. Herein, we report the first cervical EBVMCU incidentally discovered at large loop excision of the transformation zone performed for treating human papillomavirus induced high-grade squamous intraepithelial lesion. The patient was a 35-yr-old, human immunodeficiency virus-positive woman with a history of pulmonary tuberculosis. Histologic and immunohistochemical findings showed classic Hodgkin lymphoma-like features. Systemic lymphoproliferative disease was excluded by appropriate clinical and imaging modalities. This case report highlights the prototypical histologic features of cervical EBVMCU. We emphasize the importance of clinicopathologic correlation to avoid overtreatment of a lesion that can otherwise meet histologic criteria for a lymphoma. Clinicians and pathologists should familiarize themselves with this entity, as this indolent, pseudomaligant lesion typically occurs in immunocompromised patients and spontaneously regresses when the cause for the immunosuppression is addressed.
BAP1 and Claudin-4, But Not MTAP, Reliably Distinguish Borderline and Low-grade Serous Ovarian Tumors From Peritoneal Mesothelioma
Authors: Devins Kyle M. , Zukerberg Lawrence , Watkins Jaclyn C. , Hung Yin Pun , Oliva Esther
Published: May 2022

Peritoneal mesothelioma (PM) and serous neoplasms can be difficult to differentiate, particularly in small biopsies. BRCA1-associated protein 1 (BAP1) is expressed in benign tissues, but over 50% of PMs demonstrate complete loss of nuclear expression. Claudin-4, a tight junction protein, is expressed in most epithelial tumors but not in mesotheliomas. Methylthioadenosine phosphorylase (MTAP) is frequently co-deleted with cyclin-dependent kinase inhibitor 2a in mesotheliomas. These markers have proven useful in separating mesothelioma from its mimics, particularly when tumors are pleural based. In the peritoneum, BAP1 loss has been rarely reported in high-grade serous carcinomas, but overall, these markers have been minimally evaluated in ovarian serous borderline tumors and low-grade serous carcinomas. Thus, we assessed the utility of BAP1, claudin-4, and MTAP in the differential diagnosis of PM and low-grade serous neoplasms. Eighteen PM (16 epithelioid, 1 biphasic, and 1 sarcomatous), 24 low-grade serous carcinomas, and 25 serous borderline tumors were stained for BAP1, claudin-4, and MTAP. Loss of BAP1 nuclear expression was observed in 12 (67%) PM (11 epithelioid, 1 biphasic) but was retained in all serous tumors. Claudin-4 was positive in all serous tumors and negative in all PM. Complete loss of cytoplasmic MTAP was noted in 3 (17%) PMs and 1 (4%) serous borderline tumor, while all low-grade serous carcinomas showed retained expression. BAP1 loss reliably distinguishes PM from serous tumors, although it lacks sensitivity. Claudin-4 is a reliable marker to exclude PM. MTAP loss may occur in both PM and serous tumors, and thus is not useful in distinguishing these entities.
Shared Psychotic Disorder Associated With Bipolar Disorder in the Primary Case in the Context of Opioid Misuse
Authors: Livne Ofir , Sinai Omri , Lev-Ran Shaul
Published: May 2022

Bipolar disorder (BD) is a serious chronic mood disorder associated with high rates of co-occurring substance use disorders. Shared psychotic disorder (SPD) is a rare clinical phenomenon and has been reported in only a few cases of individuals diagnosed with BD. Furthermore, reports concerning SPD being induced by substance use or withdrawal are lacking. We report the case of a married couple endorsing simultaneous psychosis, a form of SPD. The primary case (the wife) had a diagnosis of BD, without any history of psychotic episodes before the current episode, while the secondary case (the husband) had a diagnosis of posttraumatic stress disorder. Both individuals were misusing prescribed synthetic opioids, and their psychosis was most likely induced by a withdrawal state. Cases of SPD involving patients with BD have rarely been reported. Considering the high rates of dual diagnoses among patients with BD, clinicians should be aware of the risk of substance-induced psychosis among these individuals and the manifestation of these psychotic episodes. This case report strengthens previous reports suggesting that SPD is a clinical entity that can occur not only in situations where the primary case involves an individual diagnosed with delusional disorder or schizophrenia, but that it may also occur when the primary case has a diagnosis of BD.
Commentary: Diagnostic Challenges
Authors: Garakani Amir
Published: May 2022

The 3 cases presented in this issue highlight diagnostic challenges in evaluating and treating patients with complicated presentations. The first case involved a man with mild neurocognitive disorder due to Alzheimer disease accompanied by depressive and anxiety symptoms and what appeared to be previously undiagnosed attention-deficit/hyperactivity disorder. The second case involved an unusual case of shared psychotic disorder involving a woman with a primary diagnosis of bipolar disorder and her husband with posttraumatic stress disorder. The third case involved a patient with a history of multiple diagnoses who presented with catatonic symptoms, obsessive-compulsive disorder characterized by religious scrupulosity, and some features of obsessive-compulsive personality disorder. These reports illustrate the challenges in evaluating and treating patients whose clinical presentations may not fit neatly into a diagnostic category or that have a nontraditional presentation.
Firearm Injury Prevention and Extreme Risk Protection Orders
Authors: Wortzel Hal S. , Simonetti Joseph A. , Ryan Arthur T. , Matarazzo Bridget B.
Published: May 2022

Extreme risk protection orders (ERPOs) represent a potential mechanism to facilitate firearm-related lethal means safety. ERPOs are a legal mechanism that enables law enforcement to temporarily remove firearms from, and prevent firearm purchase by, an individual who presents a significant danger to self or others, as determined by a court of law. While few jurisdictions currently allow mental health professionals to initiate ERPO petitions, it nonetheless seems important that clinicians be familiar with ERPOs, as clinicians may still serve an important role in disseminating information and facilitating judicious petitions. However, ERPO laws remain quite new, and the implications for mental health professionals when participating (directly or indirectly) in ERPOs remain unclear. This column introduces readers to ERPOs and offers resources to learn more about how ERPOs work across various jurisdictions.
How an Understanding of the Function of the Locus Coeruleus Led to Use of Dexmedetomidine to Treat Agitation in Bipolar Disorder: Example of Rational Development of Psychiatric Medications
Authors: Preskorn Sheldon H.
Published: May 2022

This column reviews >50 years of research on the functions subsumed by the locus coeruleus (LC) (also called the central adrenergic system). A major role of the LC is monitoring acid-base balance in the brain and responding by regulating blood-brain permeability to water and other small molecules and cerebral blood flow. The LC, through its downward projections, also regulates and coordinates respiratory and cardiac functions. Through its effect regionally or more globally depending on the stimulus and its magnitude, the LC can regulate the extracellular space in the brain, which in turn can alter ionic concentrations and thus the sensitivity of neurons to signaling. As a result of these far-reaching effects, the LC has been implicated in brain functions ranging from sleep and wakefulness to psychiatric conditions such as hyperarousal/hypervigilance, fear, agitation, anxiety, and panic attacks. This understanding of the brain functions subsumed by the LC has, in turn, led to the most recent development in the use of dexmedetomidine, an alpha-2 adrenergic agonist, to treat agitation in patients with bipolar disorder. This column also illustrates a theme discussed in a series of previous columns concerning the successful development of novel psychiatric/central nervous system drugs on the basis of an understanding of relatively simple circuits or mechanisms that underlie pathologic behavior.
Stages of Psychotherapy for Trauma and Stress-related Disorders
Authors: Horowitz Mardi
Published: May 2022

Psychotherapy technique should change as the stages of treatment for stress response syndromes progress. A formulation helps clinicians determine what to do at each stage. This progression should allow for integration of modalities of therapy. Configurational analysis provides 4 categories for organizing clinical inferences. It begins with an assessment of key symptoms and then the states of mind in which the symptoms vary because of degrees of emotional regulation. Unresolved emotional topics that lead to symptoms are then addressed in stages of exploring the meaning of memories. Finally, the self and relational schemas that lead to maladaptive patterns are inferred and lead toward integrative techniques for re-narrations and re-schematizations.
A Safe Nonsurgical Rhinoplasty Procedure
Authors: Radulesco Thomas , Braccini Frédéric , Kestemont Philippe , Winter Cécile , Castillo Laurent , Michel Justin
Published: May 2022

Nonsurgical rhinoplasty procedures are not without risks: although rare, intravascular injections of hyaluronic acid can lead to serious complications. Very few authors have reported using cannulas for filler injection in the nose. The purpose of this article is to describe how the authors perform nonsurgical rhinoplasty using a single entry point and cannulas, significantly reducing vascular and infection risks. The procedure described in this article can be applied to all indications of nonsurgical rhinoplasty. The key point of the authors’ procedure is the definition of a single, medial entry point. Using a 5-cm, 25-gauge, dome-shaped cannula, all nasal regions can be reached, from the anterior nasal spine to the nasion. The authors’ nonsurgical rhinoplasty procedure using cannulas reduces complications and provides results similar to those achieved with needles.
Circumferential Liposuction of the Thigh with Concomitant Fat Transplantation to the Infragluteal Region: A Promising Option for Preventing Postliposuction Gluteal Ptosis
Authors: Gu Yunpeng , Yang Mingzi , Sun Jingjing , Lv Qianwen , Qi Yue , Jin Ji , Liu Zhenjun , Qi Zuoliang , Ma Gui-e
Published: May 2022

Background:

Gluteal ptosis is a common complication of circumferential liposuction of the thigh. The authors propose a novel concept of combining circumferential liposuction of the thigh with concomitant fat transplantation to the infragluteal/posterior thigh junction region to prevent postliposuction gluteal ptosis.

Methods:

Patients underwent circumferential liposuction of the thigh with or without concomitant fat transplantation from 2015 to 2020 and were retrospectively reviewed. The postoperative changes in the grade of gluteal ptosis, length of hospitalization, time to recovery, postoperative complications, and patient satisfaction were evaluated.

Results:

A total of 109 patients were enrolled in this study, including 46 patients in the liposuction-only group and 63 patients in the liposuction plus fat transplantation group. There was no significant difference in fat removal volume between the liposuction-only group and the liposuction plus fat transplantation group (p = 0.152). Aggravation of gluteal ptosis occurred in 43 patients (93.5 percent) in the liposuction-only group and four patients (6.3 percent) in the liposuction plus fat transplantation group (p < 0.001). The length of hospitalization and time to recovery was not significantly different between the two groups (p = 0.402 and p = 0.423, respectively). Complications were rare in both groups. With a minimum evaluation time of 6 months, patients in the liposuction plus fat transplantation group showed significantly higher satisfaction (p < 0.001).

Conclusion:

Concomitant fat transplantation to the infragluteal/posterior thigh junction region during circumferential liposuction of the thigh is effective in preventing postliposuction gluteal ptosis and improving patient satisfaction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Prescription practices for rigid ankle-foot orthoses among UK orthotists
Authors: Eddison Nicola , Gandy Michael , Charlton Paul , Chockalingam Nachiappan
Published: May 2022

Objective:

The purpose of this study was to investigate rigid ankle-foot orthosis (AFO) prescription practices for adult men among UK orthotists.

Design:

A cross-sectional study using a survey was distributed online to UK orthotists by the British Association of Prosthetists and Orthotists to its members and through social media and orthotic networks. The survey was completed between November 1, 2020, and November 29, 2020.

Main outcome measures:

Descriptive statistics of survey results include information related to the material used, the thickness of the material, positive cast rectification, AFO reinforcement, footplate design, padding, strapping system, and height of AFO.

Results:

One hundred participants completed the survey, which equates to a response rate of 30.5% of the British Association of Prosthetists and Orthotists members targeted. A clear consensus emerged on the design of a bespoke rigid AFO for the hypothetical patient in this study, which is detailed as follows: 1) 4.5 mm copolymer polypropylene, 2) no additional reinforcement, 3) full-length footplate with mediolateral trimlines terminating behind the metatarsal heads, 4) 3-point correction with parallel sides, 5) padded VELCRO straps with D-rings at the calf and heel, 6) no forefoot or other additional strapping, 7) 3-mm PORON (international Ltd) padding at the malleoli, and 8) AFO height that finishes 2 cm below the fibular head.

Conclusions:

This study has highlighted a consensus on AFO prescription/design among UK orthotists surveyed, based on the hypothetical patient described in this study.
Optimal design and 3D printing of prosthetic socket based on the interface pressure between the socket and residual limb
Authors: Tang Jianhua , Liu Xidong , Liu Ziyi , Li Wei
Published: May 2022

Background:

At present, the quantifiable pressure distribution at the interface between the socket and stump is seldom applied in the design and fabrication of the socket.

Objectives:

This study aimed to optimize the socket based on the interface pressure of residual limb–socket, thereby avoiding excessive local load on the residual limb, reducing the load on the pressure-sensitive (PS) regions and making the limb more evenly loaded.

Methods:

The residual limb was divided into the main load-bearing regions, the pressure-tolerant regions, and the PS regions according to the carrying capacity at its different regions. Based on these bearing regions, a mathematical function was developed, which applied modifications/adjustments to the socket design in a Computer Aided Design (CAD) environment by using the adjustment function. Besides, three adjusted sockets were produced by using selective laser sintering 3D printing technology.

Results:

The wearing of the 3D-adjusted printed sockets reduced the contact interface pressures in the distal tibial region and the fibular head region by 85.6% and 84.4%, respectively. In addition, the walking distance of the subject was increased by 18.34%, and the overall pressure distribution on the stump became more uniform.

Conclusions:

The pressures in the original overpressure regions and the PS regions could reduce, whereas the pressure in the low-load regions of main load-bearing or pressure-tolerant regions could increase by modifying the socket with the pressure adjustment function. At the same time, the pressure among different regions was more uniform except for the sensitive regions.
Extended Intraoperative Longitudinal 3-Dimensional Cone Beam Computed Tomography Imaging With a Continuous Multi-Turn Reverse Helical Scan
Authors: Reynolds Tess , Ma Yiqun Q. , Kanawati Andrew J. , Constantinidis Alex , Williams Zoe , Gang Grace , Dillon Owen , Russ Tom , Wang Wenying , Ehtiati Tina , Weiss Clifford R. , Theodore Nicholas , Siewerdsen Jeffery H. , Stayman Joseph W. , O'Brien Ricky T.
Published: May 2022

Objectives

Cone beam computed tomography (CBCT) imaging is becoming an indispensable intraoperative tool; however, the current field of view prevents visualization of long anatomical sites, limiting clinical utility. Here, we demonstrate the longitudinal extension of the intraoperative CBCT field of view using a multi-turn reverse helical scan and assess potential clinical utility in interventional procedures.

Materials and Methods

A fixed-room robotic CBCT imaging system, with additional real-time control, was used to implement a multi-turn reverse helical scan. The scan consists of C-arm rotation, through a series of clockwise and anticlockwise rotations, combined with simultaneous programmed table translation. The motion properties and geometric accuracy of the multi-turn reverse helical imaging trajectory were examined using a simple geometric phantom. To assess potential clinical utility, a pedicle screw posterior fixation procedure in the thoracic spine from T1 to T12 was performed on an ovine cadaver. The multi-turn reverse helical scan was used to provide postoperative assessment of the screw insertion via cortical breach grading and mean screw angle error measurements (axial and sagittal) from 2 observers. For all screw angle measurements, the intraclass correlation coefficient was calculated to determine observer reliability.

Results

The multi-turn reverse helical scans took 100 seconds to complete and increased the longitudinal coverage by 370% from 17 cm to 80 cm. Geometric accuracy was examined by comparing the measured to actual dimensions (0.2 ± 0.1 mm) and angles (0.2 ± 0.1 degrees) of a simple geometric phantom, indicating that the multi-turn reverse helical scan provided submillimeter and degree accuracy with no distortion. During the pedicle screw procedure in an ovine cadaver, the multi-turn reverse helical scan identified 4 cortical breaches, confirmed via the postoperative CT scan. Directly comparing the screw insertion angles (n = 22) measured in the postoperative multi-turn reverse helical and CT scans revealed an average difference of 3.3 ± 2.6 degrees in axial angle and 1.9 ± 1.5 degrees in the sagittal angle from 2 expert observers. The intraclass correlation coefficient was above 0.900 for all measurements (axial and sagittal) across all scan types (conventional CT, multi-turn reverse helical, and conventional CBCT), indicating excellent reliability between observers.

Conclusions

Extended longitudinal field-of-view intraoperative 3-dimensional imaging with a multi-turn reverse helical scan is feasible on a clinical robotic CBCT imaging system, enabling long anatomical sites to be visualized in a single image, including in the presence of metal hardware.
Autonomic Function Tests, Heart Rate Variability, and Electrophysiological Evaluation in Patients With a Primary Episodic Headache: An Observational Study
Authors: Qavi Abdul , Jasrotia Rajani Bala , Maurya Pradeep Kumar , Singh Ajai Kumar , Kulshreshtha Dinkar , Ansari Arshi , Thacker Anup Kumar , Kanchan Arvind
Published: May 2022

Purpose:

Cranial autonomic symptoms are typically associated with the trigeminal autonomic cephalalgias and also present in substantial cases of migraine. Autonomic nervous system dysfunctions are also been reported in headache disorders and postulated to promote headache attacks. This study was aimed to evaluate the parasympathetic and sympathetic autonomic functions tests in patients with a episodic primary headache and to investigate, if any, electrophysiological abnormalities in the blink reflex test and sympathetic skin response test in these patients.

Methods:

In this cross-sectional study, a total of 100 patients, 50 patients each of migraine and tension-type headache attending the neurology OPD and fulfilling the diagnostic criteria of headache disorders were enrolled. Autonomic functions tests were performed in the Department of Physiology, whereas electrophysiological tests were powered by the Editorial Manager and ProduXion Manager from Aries Systems Corporation performed in the Department of Neurology.

Results:

Significant association (P < 0.05) was observed in “blood pressure response to sustained handgrip” (sympathetic activity) and “heart rate response to Valsalva maneuver” (parasympathetic activity) among patients with migraine. Although the mean sympathetic skin response latency of patients with migraine was within the normal range, it was significantly prolonged in comparison with the control group. “Blood pressure response to sustained handgrip” and “heart rate variability” were found to be significantly (P < 0.05) different in patients with a tension-type headache. The blink reflex test was observed to be normal in all patients with a headache. Patients with migraine showed a significant dysautonomia in category three of the Ewing battery for autonomic functional disability.

Conclusions:

Autonomic functional abnormality, both sympathetic and parasympathetic, does exist in patients with a primary episodic headache.
SARS-CoV-2 and Prevotella spp.: friend or foe? A systematic literature review
Authors: Tamanai-Shacoori Zohreh , Le Gall-David Sandrine , Moussouni Fouzia , Sweidan Alaa , Polard Elisabeth , Bousarghin Latifa , Jolivet-Gougeon Anne
Published: May 2022

During this global pandemic of the COVID-19 disease, a lot of information has arisen in the media and online without scientific validation, and among these is the possibility that this disease could be aggravated by a secondary bacterial infection such as Prevotella, as well as the interest or not in using azithromycin, a potentially active antimicrobial agent. The aim of this study was to carry out a systematic literature review, to prove or disprove these allegations by scientific arguments. The search included Medline, PubMed, and Pubtator Central databases for English-language articles published 1999–2021. After removing duplicates, a total of final eligible studies (n=149) were selected. There were more articles showing an increase of

Prevotella

abundance in the presence of viral infection like that related to Human Immunodeficiency Virus (HIV), Papillomavirus (HPV), Herpesviridae and respiratory virus, highlighting differences according to methodologies and patient groups. The arguments for or against the use of azithromycin are stated in light of the results of the literature, showing the role of intercurrent factors, such as age, drug consumption, the presence of cancer or periodontal diseases. However, clinical trials are lacking to prove the direct link between the presence of

Prevotella

spp. and a worsening of COVID-19, mainly those using azithromycin alone in this indication.
IDENTIFICATION OF GENOTYPE III OF HEPATITIS DELTA VIRUS IN ANDEAN AND AMAZONIAN COMMUNITIES OF PERU
Authors: Balbuena-Torres Johanna N. , Santos-Solis Lorena , Navarro-Oviedo Ronald D. , Cabezas Cesar
Published: May 2022

Objectives

to identify the genotypes of Hepatitis Delta Virus (HDV) circulating in populations of the inter-Andean valley of Huanta and three indigenous peoples of the Peruvian Amazon.

Materials and Methods

Observational and cross-sectional study, from 582 reactive samples for anti-HBc-HBV antibodies in inhabitants of the andean province of Huanta (Ayacucho) and the Amazonian towns of Matsés, Kandozi and Chapra (Loreto). Analysis was performed for HDV infection markers: anti-HDV IgM and anti-HDV IgG by ELISA using Wantai brand kits. Anti-HDV positive samples by ELISA were processed with the nRT-PCR method for the detection of HDV RNA. HDV genotype was determined by direct Sanger-type sequencing and phylogenetic analysis of the R0 fragment. 111 reference sequences from GenBank were used. The 42 sequences of the study were edited, assembled and cut with the programs Chromas 2.6.5, Bioedit v7.2, ClustalW v.1.6 of Mega v.7.0 and the Gblocks server. Phylogenetic and evolutionary analysis was performed with the following software: Beast V2.5.2, Jmodeltest v2.1.10, Tracer v1.7.1, Tree Annotator and Figtree v1.4.4. The Bayesian Yule and Birth Death skyline serial models were used, the MCMC at 30 and 80 million respectively, with the relaxed uncorrelated Exponential molecular clock. Summary and central tendency measures were calculated using the program in STATA 14.0.

Results

The mean age was 38 years (0 to 86 years), 52.75% (N=307) were women. 582 blood samples positive for anti-HBc were analyzed for anti-HVD antibodies using the ELISA method, with 101 positive samples being found. HDV RNA was detected in 49.50% of the anti-HDV ELISA reactive samples. Phylogenetic analysis determined the presence of genotype 3.

Conclusions

The presence of HDV genotype 3 in Andean and Amazonian communities of Peru is evidenced.
Durability of the immune response to a third BNT162b2 dose; five months follow-up
Authors: Gilboa Mayan , Regev-Yochay Gili , Mandelboim Michal , Indenbaum Victoria , Asraf Keren , Fluss Ronen , Amit Sharon , Mendelson Ella , Doolman Ram , Afek Arnon , Freedman Laurence S. , Kreiss Yitshak , Lustig Yaniv
Published: May 2022

Background

Two doses of the BNT162b2 vaccine yielded high effectiveness that wanes within several months. The third dose was effective in mounting a significant humoral and cellular immune response..

Methods

We followed BNT162b2-vaccinated health-care workers monthly for IgG and neutralizing antibody (NeutAb) titers. Avidity, T-cell activation and microneutralization of sera against different variants of concern (VOC) were assessed for a sub-cohort. Linear mixed models were used to compare the durability of the second and third doses, and to assess if Omicron breakthrough infections were associated with waning dynamics.

Results

Overall 3972 participants with a third dose were followed, the rate of waning of IgG and NeutAb was slower after the third (1.32%/day and 1.32%/day, respectively) compared to the second (2.26%/per day and 3.34%/day) dose. Live-neutralization of Omicron VOC was lower compared to previous strains and demonstrated similar waning from 111 (95%CI:75-166) to 26 (95%CI:16-42) within 4 months. Mean T cell activity decreased from 98±5.4 T cells/106 PBMC to 59±9.3, within 3-5 months. Omicron breakthrough infections were associated with lower IgG peak (ratio of means 0.86 95%CI 0.80-0.91), and among participants over 65y with faster waning of both IgG and NeutAb (ratio of mean rates 1.40 95% CI 1.13-1.68 and 3.58 95% CI 1.92-6.67). No waining in IgG avidity was obsereved during 112 days after the 3rd dose.

Conclusion

The third dose is more durable than the second dose, yet Omicron is relatively resistant to direct neutralization. The level of humoral response may predict breakthrough infections.
Childhood Stunting and Its Associated Factors in Ethiopia
Authors: Gobena Woldemariam Erkalo
Published: May 2022

Child malnutrition is the root cause of nearly half (45%) of all child deaths, especially in low-income nations. Ethiopia has the highest frequency of stunting among Sub-Saharan African countries, at 38 percent. The study’s major goal was to use cluster specific models to identify risk factors for stunting in Ethiopian children under the age of five. The data was gathered from the EDHS 2016, a nationally representative survey of children aged 0 to 59 months. The research was carried out using generalized linear mixed models from the cluster specific model family. The variables child’s age, mother’s education level, mother’s BMI, place of residence, wealth index, and prior birth interval were determined to be important drivers of child malnutrition in Ethiopia as a result of the analysis. According to the findings, children with a shorter previous birth interval (less than 24 months) were more likely to be stunted than those with a longer previous birth interval. Rural Ethiopian children were more likely than urban Ethiopian children to be stunted. It is advised that in order to reduce childhood malnutrition, parents’ awareness and implementation of proper young child feeding practices, as well as frequent growth monitoring and appropriate and timely interventions, should be prioritized.
A comparison of mtDNA deletion mutant proliferation mechanisms
Authors: Holt Alan G , Davies Adrian M
Published: May 2022

In this paper we use simulation methods to investigate the proliferation of deletion mutations of mitochondrial DNA in neurons. We simulate three mtDNA proliferation mechanisms, namely, random drift, replicative advantage and vicious cycle. For each mechanism, we investigated the effect mutation rates have on neuron loss within a human host. We also compare heteroplasmy of each mechanism at mutation rates that yield the levels neuron loss that would be associated with dementia. Both random drift and vicious cycle predicted high levels of heteroplasmy, while replicative advantage showed a small number of dominant clones with a low background of heteroplasmy.
Trogocytic-molting of T-cell microvilli controls T-cell clonal expansion
Authors: Park Jeong-Su , Kim Jun-Hyeong , Soh Won-Chang , Lee Kyung-Sik , Kim Chang-Hyun , Chung Ik-Joo , Lee Sunjae , Kim Hye-Ran , Jun Chang-Duk
Published: May 2022

Internalization of the T-cell antigen receptor (TCR) is intimately linked to T-cell activation: a phenomenon thought to be related to the “exhaustion” of T-cell responses. To date, however, no report has considered that during physical interaction with cognate antigen-presenting cells, T cells release many TCRs via T-cell microvilli particles, which are derived from finger-like membrane structures (microvilli) in a combined process of trogocytosis and enzymatic vesiculation and correspond with the loss of membrane TCRs and many external membrane components. Surprisingly, in contrast to TCR internalization, this event leads to rapid upregulation of surface TCRs and remarkable metabolic reprogramming of cholesterol and fatty acids synthesis to meet the demands of clonal expansion, which drives multiple rounds of division and cell survival. We called this event “trogocytic-molting,” which represents an intrinsic molecular basis of T-cell clonal expansion by which T cells gain increased sensitivity to low antigen concentrations.

TEASER

“Trogocytic-molting,” led to the rapid upregulation of surface TCRs and tremendous metabolic reprogramming to meet the demands of clonal expansion.
Connecting single-cell ATP dynamics to overflow metabolism, cell growth and the cell cycle in Escherichia coli
Authors: Lin Wei-Hsiang , Jacobs-Wagner Christine
Published: May 2022

Adenosine triphosphate (ATP) is a universal energy-carrying molecule that cells consume and regenerate in vast amounts to support growth. Despite this high turnover, bacterial cultures maintain a similar average concentration of ATP even when the carbon source conditions lead to large differences in population growth rate. What happens in individual bacterial cells is, however, less clear. Here, we use the QUEEN-2m biosensor to quantify ATP dynamics in single Escherichia coli cells in relation to their growth rate, metabolism, cell cycle, and cell lineage. We find that ATP dynamics are more complex than expected from population studies and are associated with growth rate variability. Under a nutrient-rich condition, cells can display large fluctuations in ATP level that are partially coordinated with the cell cycle. Abrogation of aerobic acetate fermentation (overflow metabolism) through genetic deletion considerably reduces both the amplitude of ATP level fluctuations and the cell cycle trend. Similarly, growth in media in which acetate fermentation is lower or absent results in reduction of ATP level fluctuation and cell cycle trend. This suggests that overflow metabolism exhibits temporal dynamics, which contributes to fluctuating ATP levels during growth. Remarkably, at the single-cell level, growth rate negatively correlates with the amplitude of ATP fluctuation for each tested condition, linking ATP dynamics to growth rate heterogeneity in clonal populations. Our work highlights the importance of single-cell analysis in studying cellular energetics and its implication to phenotypic diversity and cell growth.
Thermal cycling hyperthermia sensitizes non-small cell lung cancer A549 cells to EGFR-tyrosine kinase inhibitor Erlotinib
Authors: Lin Guan-Bo , Chen Wei-Ting , Kuo Yu-Yi , Liu Hsu-Hsiang , Chen You-Ming , Leu Shr-Jeng , Chao Chih-Yu
Published: May 2022

Molecular targeted therapy has emerged as a mainstream treatment for non-small cell lung cancer (NSCLC), the most common lung cancer, which has been the leading cause of cancer death in both genders. Erlotinib (Erl), a targeted therapy inhibiting epidermal growth factor receptor (EGFR) pathways, has been proved to have noticeable response rate for NSCLC cells. However, limited efficacy arises due to intrinsic and acquired resistance among most NSCLC patients. Therefore, sensitizers are required to potentiate the efficacy of Erl in NSCLC treatment. The study proposed a novel thermal therapy, thermal cycling hyperthermia (TC-HT), as a supplement to amplify the effects of Erl. We found that TC-HT remarkably reduced the half-maximal inhibitory concentration (IC50) of Erl to as little as 0.5 μM and demonstrated that TC-HT could sensitize A549 NSCLC cells to Erl via the downstream of EGFR signaling cascades. Furthermore, combination treatment induced G2/M cell cycle arrest, and inhibition of cell proliferation and migration. Besides, via raising the high temperature of TC-HT slightly, TC-HT treatment alone can produce excellent antineoplastic effect without hurting the normal cells. The method is expected to be applicable to other combination therapies and may be a starter for more sophisticated, side-effect-free anticancer treatments.
Effect of Digoxin on Interstage Outcomes following Stage I Palliation for Functionally Univentricular Hearts: A Systematic Review and Meta-Analysis
Authors: Loomba Rohit S. , Rausa Jacqueline , Villarreal Enrique , Farias Juan S. , Flores Saul
Published: May 2022

Objectives

The goal of this systematic review and meta-analysis is to investigate the effects of digoxin on outcomes following stage I palliation for functionally univentricular hearts.

Data Sources

We conducted electronic searches of PubMed, Ovid and Cochrane.

Study Selection

Inclusion criteria included publication dates 1970–2018, children with functionally univentricular hearts between stage I and stage II palliation who received digoxin were compared to those who did not.

Data Extraction

We identified 148 unique citations; 5 full-text articles were included in the final review. Data from 4 studies was pooled for meta-analysis.

Data Synthesis

A total of 4 studies with 1,498 patients were included in the final analyses. Patient enrollment occurred between 2003 and 2013. A majority of patients were born full-term and approximately 25% were diagnosed with a syndrome. The most common cardiac diagnosis was hypoplastic left heart syndrome (70%). The most common initial surgical palliation was the Norwood procedure with a right ventricle to pulmonary artery conduit. The total amount of deaths was 121 (12 digoxin group versus 109 no digoxin group). The interstage mortality was reduced in the digoxin group [OR 0.25(95% CI 0.14 to 0.47)]. There was no statistically significant difference in the presence of arrhythmias or other complications.

Conclusions

This systematic review and meta-analysis suggests that digoxin significantly decreases interstage period mortality with a concurrent significant decrease in weight for age. The odds of arrhythmia or other complications are not significantly different with digoxin based on current data.
Protection against omicron severe disease 0-7 months after BNT162b2 booster
Authors: Amir Ofra , Goldberg Yair , Mandel Micha , Bar-On Yinon M. , Bodenheimer Omri , Freedman Laurence , Alroy-Preis Sharon , Ash Nachman , Huppert Amit , Milo Ron
Published: May 2022

Following a rise in cases due to the delta variant and evidence of waning immunity after 2 doses of the BNT162b2 vaccine, Israel began administering a third BNT162b2 dose (booster) in July 2021. Recent studies showed that the 3rd dose provides a much lower protection against infection with the omicron variant compared to the delta variant and that this protection wanes quickly. In this study, we used data from Israel to estimate the protection of the 3rd dose against severe disease up to 7 months from receiving the booster dose. The analysis shows that protection conferred by the 3rd dose against omicron did not wane over a 7-month period and that a 4th dose further increased protection, with a severe disease rate approximately 3-fold lower than in the 3-dose cohorts.
Structure of the RAF1-HSP90-CDC37 complex reveals the basis of RAF1 regulation
Authors: García-Alonso Sara , Mesa Pablo , de la Puente Ovejero Laura , Aizpurua Gonzalo , Lechuga Carmen G , Zarzuela Eduardo , Santiveri Clara M , Sanclemente Manuel , Muñoz Javier , Musteanu Mónica , Campos-Olivas Ramón , Martínez-Torrecuadrada Jorge , Barbacid Mariano , Montoya Guillermo
Published: May 2022

RAF kinases are RAS-activated enzymes that initiate signalling through the MAPK cascade to control cellular proliferation, differentiation, and survival. Here, we describe the structure of the full-length RAF1 protein in complex with HSP90 and CDC37 obtained by cryo-electron microscopy. The reconstruction reveals a RAF1 kinase with an unfolded N-lobe separated from its C-lobe. The hydrophobic core of the N-lobe is trapped in the HSP90 dimer while CDC37 wraps around the chaperone and interacts with the N- and C-lobes of the kinase. The structure indicates how CDC37 can discriminate between the different members of the RAF family. Our structural analysis also reveals that the folded RAF1 assembles with 14-3-3 dimers, suggesting that after folding follows a similar activation as B-RAF. Finally, disruption of the interaction between CDC37 and the DFG segment of RAF1 unveils potential vulnerabilities to attempt the pharmacological degradation of RAF1 for therapeutic purposes.
Evaluation of Cognitive Function in the Dog Aging Project: Associations with Baseline Canine Characteristics
Authors: Yarborough Sarah , Fitzpatrick Annette , Schwartz Stephen M. ,   Dog Aging Project Consortium
Published: May 2022

Canine Cognitive Dysfunction (CCD) is a neurodegenerative disease in aging dogs. It has been described previously in relatively small cohorts of dogs using multiple different rating scales. This study aimed to use a minimally modified CCD rating scale developed by previous researchers to describe the prevalence of CCD more thoroughly in a large, nationwide cohort of companion dogs participating in the Dog Aging Project (DAP). Associations between various canine characteristics, predicted lifespan quartiles, and CCD were examined using univariable and multivariable logistic regression models and Receiver Operating Curve (ROC) analysis.

When controlling for all other characteristics, the odds of CCD increased 52% with each additional year of age. Among dogs of the same age, health status, breed type, and sterilization status, odds of CCD were 6.47 times higher in dogs who were not active compared to those who were very active. When controlling for age, breed type, activity level, and other comorbidities, dogs with a history of neurological, eye, or ear disorders had higher odds of CCD. Lifespan quartile analysis showed excellent discriminating ability between CCD positive and negative dogs. Weight-based lifespan quartile estimation could therefore serve as a tool to inform CCD screening by veterinarians.