bluuebunny/crossref_metadata_2025 huggingface dataset:
Donor selection for multiorgan transplantation
Authors: Hsiao Stephanie , Khush Kiran K.
Published: November 2021

Purpose of review

There is limited data and guidance on donor selection for multiorgan transplantation. In this article, we review the current Organ Procurement and Transplantation Network policy on multiorgan allocation and the ideal donor criteria for each specific organ, in order to provide a framework to guide donor selection for various scenarios of multiorgan transplantation, including heart-kidney, heart-lung, heart-liver and heart-kidney-liver transplant procedures.

Recent findings

Combined heart-kidney transplantation is the most common multiorgan transplant procedure and requires the most stringent HLA matching to ensure optimal graft survival. Using the virtual crossmatch and desensitization therapies can shorten waitlist times without increasing posttransplant rejection or mortality rates. The ideal heart-lung donor tends to be younger than other multiorgan transplants, and more tolerant to HLA mismatch, but ideally requires donors with no prior history of smoking, a short period of time on mechanical ventilation, adequate oxygenation and absence of pulmonary infection. The ideal heart-liver donor is often driven by criteria specific to the donor heart. Finally, several observational studies suggest that livers are more tolerant to HLA mismatch than other organs, and offer some degree of immune protection in combined organ transplants.

Multiorgan transplantation is a steadily growing field. The required short ischemic time for the donor heart is often the limiting factor, as well as the scarcity of appropriate donors available within geographical confines. In general, as with single organ transplantation, younger age, size matching, few medical comorbidities and HLA compatibility confer the best posttransplant outcomes.
Novel biomarkers of chronic lung allograft dysfunction: is there anything reliable?
Authors: Verleden Stijn E. , Verleden Geert M.
Published: November 2021

Purpose of review

Chronic lung allograft dysfunction (CLAD) remains a major barrier preventing long-term survival following lung transplantation. As our clinical knowledge regarding its definition and presentation has significantly improved over the last years, adequate biomarkers to predict development of CLAD, phenotype of CLAD or prognosis post-CLAD diagnosis are definitely needed.

Recent findings

Radiological and physiological markers are gradually entering routine clinical practice. In-depth investigation of biological samples including broncho-alveolar lavage, biopsy and serum has generated potential biomarkers involved in fibrogenesis, airway injury and inflammation but none of these are universally accepted or implemented although progress has been made, specifically regarding donor-derived cell-free DNA and donor-specific antibodies.

Although a lot of promising biomarkers have been put forward, a very limited number has made it to routine clinical practice. Nevertheless, a biomarker that leads to earlier detection or more adequate disease phenotyping would advance the field enormously.
A National Study to Compare Effective Management of Constipation in Children Receiving Concurrent Versus Standard Hospice Care
Authors: Lindley Lisa C. , Keim-Malpass Jessica , Cozad Melanie J. , Mack Jennifer W. , Svynarenko Radion , Fornehed Mary Lou Clark , Stone Whitney , Qualls Kerri , Hinds Pamela S.
Published: November 2021

Constipation is a distressing and uncomfortable symptom children experience at end of life. There is a gap in knowledge about how different approaches to hospice care delivery might improve pediatric symptom management of constipation. The purpose of this study was to evaluate the effectiveness of pediatric concurrent hospice versus standard hospice care to manage constipation. Medicaid data (2011-2013) were analyzed. Children who were younger than 21 years enrolled in hospice care and had a hospice enrollment between January 1, 2011, and December 31, 2013, were included. Instrumental variable analysis was used to test the effectiveness of concurrent versus standard hospice care. Among the 18 152 children, approximately 14% of participants were diagnosed or treated for constipation from a nonhospice provider during hospice enrollment. A higher proportion of children received nonhospice care for constipation in concurrent hospice care, compared with standard hospice (19.5% vs 13.2%), although this was not significant (β = .22, P < .05) after adjusting for covariates. The findings demonstrated that concurrent care was no more effective than standard hospice care in managing pediatric constipation. Hospice and nonhospice providers may be doing a sufficient job ordering bowel regimens before constipation becomes a serious problem for children at end of life.
Effects of an Interprofessional Spiritual Care Education Project
Authors: Smith Christy , Lakin Tracy
Published: November 2021

Spiritual care is a critical aspect of end-of-life care that is often undervalued and underaddressed by hospice health care teams. The purpose of this quality improvement project was to determine if the implementation of an evidence-based spiritual care protocol changed practices regarding the initial assessment of spiritual needs, frequency of reassessment of needs, the inclusion of spiritual interventions, and staff perspectives on spiritual care. The preimplementation and postimplementation data evaluation displayed increased compliance with spiritual needs assessment within 5 days of admission, increased reassessment intervals, an increase in the percentage of interactions that included spiritual interventions, and improved staff perspectives on spiritual care. The findings of the study support implementation of a spiritual care protocol in hospice patients.
Palliative Wound Care
Authors: Walsh Anne
Published: November 2021

Patients with advanced illness may present to palliative care or hospice with unmanaged symptoms that may be exacerbated by the presence of a wound. The wound can be a constant reminder to the patient and caregiver of the underlying illness. Distressing symptoms such as wound pain, odor, bleeding, and/or excessive exudate may impede the patients' ability to spend quality time with loved ones when they need them the most. Although patients may present with wounds of varying etiologies, the most common wounds seen in this patient population are pressure-related injuries. However, there is a shortage of both wound and palliative specialized clinicians. Telehealth and the use of other technology can be a way to address this shortage. This will grant access to a broader number of patients to ensure appropriate wound care plans are in place to meet the goals of care. Although wound healing may not always be possible in this patient population, having access to specialized wound and palliative experts can improve the quality of life for patients and their caregivers.
Posturographic Findings in Patients With Psychological Dizziness
Authors: Matsumura Yachiyo , Ito Taeko , Yamanaka Toshiaki , Kitahara Tadashi
Published: November 2021

Background:

The diagnosis and treatment of patients with psychogenic vertigo (PSY) is difficult because of the lack of reliable objective findings for this condition. We examined the characteristics of foam posturography in patients with peripheral vestibular disorders (PVD) and those with PSY. In particular, we focused on the objective findings of foam posturography in PSY.

Methods:

Between January 2010 and December 2011, 2-legged stance tasks were conducted in patients with vertigo/dizziness under 4 conditions: eyes opened with/without foam rubber and eyes closed with/without foam rubber. In terms of the velocity of movement of the center of pressure, we examined Romberg ratios, that is, the ratios of changes in visual conditions under the fixed foam rubber conditions, and foam rubber ratios, that is, the ratios of changes in foam rubber conditions under fixed visual conditions. These ratios were compared among 3 groups: healthy controls (CONT) (n=195), PVD (n=178), and PSY (n=32).

Results:

Romberg ratios using foam rubber in the PVD group were significantly higher than those in the CONT group. Those in the PSY group were significantly lower. Likewise, the foam rubber ratios in the PVD group were significantly higher than those in the CONT group when the eyes were closed. Those in the PSY group were significantly lower.

Conclusion:

Judging from scores in Romberg ratios using foam rubber and foam rubber ratios when eyes were closed, foam posturography might have the potential to differentiate PSY from PVD.
HSV-Encephalitis Resembling Acute Cerebral Infarction in a Patient With Atrial Fibrillation
Authors: Kargiotis Odysseas , Oikonomi Katerina , Geka Aliki , Psychogios Klearchos , Safouris Apostolos , Zis Panagiotis , Kararizou Evangelia , Papadionisiou Panagiotis , Tsivgoulis Georgios
Published: November 2021

Introduction:

Herpes simplex virus-1 (HSV-1) encephalitis, the most common and potentially life-threatening type of encephalitis, may rarely present as a stroke mimic. Prompt diagnosis is of paramount importance for the timely initiation of antiviral treatment and to avert intravenous thrombolysis.

Case Report:

A 60-year-old man with a history of lone paroxysmal atrial fibrillation without prior antithrombotic treatment was admitted due to mild gait unsteadiness and intermittent dysarthria of acute onset. On admission, the patient was afebrile, whereas neurological examination revealed only a mild pronator drift on the left. Brain magnetic resonance imaging (MRI) showed an extensive right temporo-occipital and thalamic lesion with restricted diffusion and 3 small-sized hemorrhagic foci. Brain MR-angiography did not show large vessel stenosis or occlusion. On the basis of careful observation and the depiction of several imaging discrepancies, such as early vasogenic edema and hemorrhagic transformation, as well as uncus involvement, but also the lack of significant neurological deficits despite the size of the brain lesion we suspected viral encephalitis which was confirmed by the detection of HSV-1 DNA in the cerebrospinal fluid.

Conclusion:

HSV-encephalitis might occasionally result in the development of unilateral brain MRI lesions with extensive cytotoxic edema, resembling an acute ischemic stroke. Therefore, HSV-encephalitis must be considered in the differential diagnosis of acute ischemic stroke with atypical presentation. The presence of a significant dissociation between the brain MRI lesion volume and the neurological deficits, as well as certain brain MRI imaging discrepancies might serve as “red flags” to extend the diagnostic workup.
MR Three-Territory Sign in Cancer-Associated Hypercoagulation Stroke (Trousseau Syndrome)
Authors: Finelli Pasquale F.
Published: November 2021

Background:

Stroke in the setting of three-territory lesion pattern on magnetic resonance-diffusion-weighted imaging “three-territory sign” (TTS) is predominately due to cancer-associated hypercoagulation (CAH). Our goal is to determine the frequency with which “TTS” is overlooked as a diagnostic feature of cancer-associated hypercoagulation stroke.

Methods:

Over a 4-year period (October 2016 to October 2020), stroke admissions with magnetic resonance imaging defined three-territory diffusion-weighted imaging lesions were identified. Patients were prospectively accrued in an observational study from the neurology service at Hartford Hospital, a 938 bed facility with a comprehensive stroke center with 2792 stroke admissions during the study period.

Results:

Twenty-two patients met selection criteria, 4 due to infectious endocarditis, 16 due to stroke from CAH and 2 with no identifiable etiology. Of the 16 CAH patients, 5 were male and 11 female, mean age=72 (range: 47 to 91). Cancer type (biopsy proven unless noted) was cholangiocarcinoma=3, adenocarcinoma of lung=3, adenocarcinoma of breast=1, pancreatic carcinoma=3 (2 biopsy, 1 ultrasound), adenocarcinoma, origin unknown=1, non−small cell carcinoma of lung=2, carcinoid=1, ovarian carcinoma=1, lung mass (not biopsied)=1. Malignancy was known in 7 and occult in 9 at stroke presentation. Consideration of malignancy-related hypercoagulation as the cause of stroke was appreciated in 1 of 16 radiology reports and in 4 of 16 neurology admission notes.

Conclusion:

TTS is a frequently missed diagnostic magnetic resonance feature in cancer-associated hypercoagulation stroke and often heralds occult malignancy.
Effect of the Implementation of a Local Care Pathway on the Transient Ischemic Attack Management in Emergency Departments
Authors: Chabbert Pauline , Lamboley Loic , Souquet Odile , Haesebaert Julie , Termoz Anne , Schott Anne-Marie , Lecoanet André , Douplat Marion , Benhamed Axel , Nighoghossian Norbert , Mechtouff Laura
Published: November 2021

Background:

Recent studies have demonstrated that urgent care decreases the risk of subsequent stroke after transient ischemic attack (TIA). In response to heterogeneous TIA management observed in our area, we developed a structured pathway, in accordance with current guidelines and adapted to local resources. We aim to assess the effect of local implementation of this care pathway on TIA management in emergency departments (EDs) in the Rhône area (France).

Patients and Methods:

EDs of 5 centers that had a minimum of 30 TIA/year in Lyon and Bourgoin-Jallieu participated. The first 30 consecutive patients who had a TIA as main diagnosis admitted to one of these EDs from January 1 to December 31, 2013 and from January 1 to December 31, 2016, that is, before-and-after care pathway implementation, respectively, were retrospectively included in the study. The primary outcome was the adequate management of TIA defined as having had appropriate workup and antithrombotic treatment within 24 hours.

Results:

A total of 141 patients were included in 2013 and 150 in 2016. There was a significant increase of complete (intracrania and extracranial) vessel imaging from 2013 to 2016 (n=42, 29.8% in 2013 vs. n=118, 78.7% in 2016; P<0.001). Computed tomography angiography was more often performed to assess intracranial and/or extracranial vessel imaging in 2016 compared with 2013 (n=54, 34.8% in 2013 vs. n=116, 77.3% in 2016; P<0.001). Overall, the rate of patients receiving adequate management significantly increased from 2013 to 2016 (n=36, 25.5% in 2013 vs. n=101, 67.3% in 2016; P<0.001).

Conclusions:

Implementation of a local care pathway, in accordance with current guidelines and adapted to local resources, improved TIA management in EDs, mostly by increasing the rate of vessel imaging by computed tomography angiography.
Endovascular Therapy Versus Anticoagulation for Treatment of Cerebral Venous Sinus Thrombosis
Authors: Xu Zhongmou , Li Xiang , Feng Dongxia , Wang Tianyi , Xu Xiang , Deng Ruming , Zhou Xinmin , Chen Gang
Published: November 2021

Background:

Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke that mainly affects the young. Anticoagulation (AC) with heparin is the mainstay of treatment for CVST. Although highly anticipated, endovascular therapy (ET) including local thrombolysis and mechanical thrombectomy has been controversial.

Review Summary:

To compare the effectiveness and safety of ET with AC for patients with confirmed CVST, we systematically searched PubMed, Embase, and Cochrane Library from the earliest date to February 2020. Data on the total number of patients in each treatment group and the exact number of patients for each outcome were separately extracted from 10 studies with 891 patients.

Our Results show that ET has a higher mortality rate compared with AC [odds ratio (OR)=1.95; 95% confidence interval (CI), 1.19-3.18; P=0.008<0.01] and has lower probability of good outcome (OR=0.48; 95% CI, 0.23-1.02; P=0.056). ET leads to a higher risk of complications than AC (OR=5.29; 95% CI, 1.17-23.95; P=0.030<0.05). No difference was found in recurrence rate between 2 treatments (OR=0.85; 95% CI, 0.31-2.35; P=0.761).

Conclusions:

ET is related to a higher mortality, fewer good outcome and possibly more complications compared with AC. The risks of ET should be weighed in every individualized therapeutic decision.
Comparison of Acupuncture and Sham Acupuncture in Migraine Treatment
Authors: Li Mao , Wang Weijun , Gao Wen , Yang Dongdong
Published: November 2021

Background:

Acupuncture is widely used for treating migraine; however, evidence of its efficacy when compared with sham acupuncture is equivocal. This study aimed to compare the evaluate efficacy of acupuncture versus sham acupuncture in migraine treatment.

Methods:

We searched PubMed, the Cochrane Library, Web of Science, and EMBASE databases from their inception to April 25, 2021, for randomized controlled trials. The outcome measurement included response rate, migraine days, intensity, and frequency.

Results:

Twenty randomized controlled trials involving 2725 patients were included. Pooled data suggested that acupuncture was superior to sham acupuncture [mean difference (MD)=−0.52, 95% confidence interval (CI): −0.71 to −0.34, P<0.00001] in reducing the migraine frequency after treatment and follow-up (MD=−0.51, 95% CI: −0.70 to −0.32, P<0.00001). In reducing Visual Analog Scale, acupuncture was superior to sham acupuncture (MD=−0.72, 95% CI: –1.17 to −0.27, P=0.002) after treatment, and also superior to sham acupuncture (MD=−0.82, 95% CI: −1.31 to −0.33, P=0.001) on the follow-up. As for responder rate, acupuncture’s efficacy was better than sham acupuncture (relative risk=1.28, 95% CI: 1.00-1.64, P=0.05). However, the reduction of migraine days in the acupuncture group was not significantly different from that in the sham acupuncture group after treatment (MD=−0.62; 95% CI: −1.31 to 0.08; P=0.08) and on the follow-up (MD=−0.68; 95% CI: −1.52 to 0.17; P=0.12).

Conclusions:

Acupuncture appears to be an effective treatment modality for migraine. Compared with sham acupuncture, acupuncture had greater improvements in migraine frequency, Visual Analog Scale, and responder rate, but there was no statistically significant difference for the number of migraine days.
Easy-To-Perform Dual Immunohistochemistry Can Solve Problems in Hematopathology
Authors: Poveda Julio , Cassidy Daniel P. , Zhou Yi , Chapman Jennifer
Published: November 2021

Immunohistochemical analysis has become an integral component in the diagnostic work up of hematopoietic neoplasms. It is not uncommon that visualization of single protein expression by immunohistochemistry among cells of interest may become a difficult task. Common scenarios of such include extensive colonization of germinal centers in the differential diagnosis of marginal zone lymphoma and follicular lymphoma, low-level bone marrow involvement by lymphoma and paucity of neoplastic lymphocytes in the setting of numerous background reactive lymphocytes, among others. For this reason, we have developed a variety of easy-to-employ dual-color dual-antibody immunohistochemical assays to aid in solving these diagnostic dilemmas. Herein, we share examples of our use of dual immunohistochemistry to illustrate its beneficial and practical objective.
The Korea National Patient Safety Incidents Inquiry Survey: Characteristics of Adverse Events Identified Through Medical Records Review in Regional Public Hospitals
Authors: Kim Min Ji , Seo Hee Jung , Koo Hong Mo , Ock Minsu , Hwang Jee-In , Lee Sang-Il
Published: November 2021

Objectives

In 2019, the Korean National Patient Safety Incidents Inquiry was conducted in the Republic of Korea to identify the national-level incidence of adverse events. This study determined the incidence and detailed the characteristics of adverse events at 15 regional public hospitals in the Republic of Korea.

Methods

Medical records data of 500 randomly selected patients (discharged in 2016) were extracted from each of the 15 studied hospitals and reviewed in 3 stages. First, for each hospital, 2 nurses independently reviewed the medical records, using 41 screening criteria. Second, 2 physicians independently reviewed the records of those patients with at least 1 screening criterion from the first stage for adverse events occurrence and their characteristics. Third, a 9-member committee conducted a final review and compiled the final adverse event report.

Results

Among 7500 patients, 4159 (55.5%) had at least 1 screening criterion; 745 (9.9%) experienced 901 adverse events (incidence, 12.0%). By type of institution, adverse event incidence varied widely from 1.2% to 45.6%. In 1032 adverse events, the majority (33.5%) were “patient care–related.” By severity, the majority (638; 70.8%) were temporary, requiring intervention, whereas 38 (4.2%) resulted in death. The preventability score was high for “patient care–related” and “diagnosis-related” adverse events. Duration of hospitalization was extended for 463 (44.9%) adverse events, with “diagnosis-related” (30.8%) and “surgery/procedural-related” (30.1%) types extended by at least 21 days.

Conclusions

A review of medical records aids in identifying adverse events in medical institutions with varying characteristics, thus helping prioritize interventions to reduce their incidence.
Reliability and validity of the Turkish version of the satisfaction module of the Orthotics and Prosthetics Users' Survey
Authors: Demirdel Senem , Ulaş Kardem , Erol Çelik Seher , Karahan Sevilay , Topuz Semra
Published: November 2021

Background:

Evaluation of prosthesis and orthosis (P&O) devices and service satisfaction in patients using P&O are important to understand the patient perspective and improve the quality of devices and the services.

Objective:

The aim of this study was to translate the original Orthotics and Prosthetics Users' Survey (OPUS) satisfaction module into Turkish and examine its psychometric properties in lower limb P&O users.

Study Design:

Cross-sectional study.

Methods:

The Turkish versions of the OPUS-Client Satisfaction with Device (CSD) and Service (CSS) modules were applied to 157 individuals using a lower limb prosthesis or orthosis. The retest of the survey was applied 5–7 days later. Intraclass correlation coefficient was used to determine test–retest reliability, and Cronbach alpha was used to determine internal consistency. Criterion validity was evaluated using the Nottingham Health Profile. Exploratory factor analysis was used to examine the factor structure of the Turkish version of the OPUS satisfaction module.

Results:

The test–retest correlation (intraclass correlation coefficient = 0.92 for CSD and 0.91 for CSS) and internal consistency (Cronbach's alpha = 0.84 for CSD and 0.95 for CSS) were high. A statistically significant correlation was found between the OPUS CSD and CSS modules and the Nottingham Health Profile (r = −0.325 for CSD module, r = −0.381 for CSS module, P < 0.001). The factor analysis revealed one-factor structure for both modules.

Conclusions:

This study demonstrated the reliability and validity of the Turkish version of the OPUS satisfaction module, and it provides a useful starting point for future studies on this survey.
The role of Gram-negative bacteria in skin and soft tissue infections
Authors: Russo Alessandro , Trecarichi Enrico Maria , Torti Carlo
Published: November 2021

Purpose of review

Skin and soft tissue infections (SSTIs) are a leading cause of morbidity, emergency department visits and hospitalization. In recent years, the spread of carbapenem-resistant gram-negative bacteria (GNB) is also increasing in SSTIs. However, the armamentarium of available drugs is recently expanding as well. In this review, we reported the most recent data and about management and treatment of SSTIs caused by GNB, mainly for the treatment of carbapenem-resistant Enterobacterales (CRE), Pseudomonas spp and Acinetobacter spp.

Recent findings

The increasing incidence of carbapenem-resistant GNB is challenging for management and treatment, considering the high rate of inappropriate empiric and targeted antimicrobial treatments. The role of new antibiotics, mainly licensed for the treatment of other infections, is an object of continuous debate. As a matter of fact, no specific clinical trials on SSTIs have been performed for new drugs; however, recent data about the use in real life of new compounds in clinical practice are available.

Some recently approved drugs are actually considered the backbone of targeted therapy in patients with severe infections caused by susceptible carbapenem-resistant GNB strains. Prompt diagnosis of cSSTIs is crucial and, when necessary, surgical debridement for source control of infection is the milestone of the treatment. The physicians should be confident to identify patients at high risk for multidrug-resistant pathogens to minimize inappropriate empiric therapy.
Spasticity, Pain, and Fatigue
Authors: Bhimani Rozina , Chappuis Diane , Mathiason Michelle A. , Anderson Lisa Carney
Published: November 2021

Purpose

The purpose of this study was to determine whether spasticity, pain, and fatigue symptoms were related to functional outcomes in people with stroke.

Design

A longitudinal correlation design was used.

Methods

Twenty-two stroke patients experiencing spasticity, pain, and fatigue were followed for 7 days over 6 weeks: 3 days in acute rehabilitation units, 3 days postdischarge to home/community, and an additional 1 day at 1 month postdischarge. Demographics, numeric ratings, and PROMIS tools were used to determine associations over time.

Results

Pain was related to fine motor activities on admission. Fatigue was significantly associated with activities of daily living, motor functions, mobility, and ability to perform physical tasks at 1 month. Spasticity was significantly related to activities of daily living, pain experiences and fatigue at 1 month.

Conclusions

Symptoms of spasticity, pain, and fatigue were associated with functional outcomes in this sample of patients.

Clinical Relevance to Rehabilitation Nursing

Symptoms can influence physical recovery; therefore, nurses could improve care through recognition of suspected correlation of symptoms in people with stroke.
MicroRNA-31 inhibits traumatic brain injury-triggered neuronal cell apoptosis by regulating hypoxia-inducible factor-1A/vascular endothelial growth factor A axis
Authors: Qian Yan , Li Xin , Fan Raofei , Li Qiaofen , Zhang Yang , He Xiaona , Yang Wei , Sun Wei , Lv Shaokun
Published: November 2021

MicroRNAs are dysregulated in traumatic brain injury and are involved in neuronal cell behaviors. Previous studies identified miR-31 as a spinal cord injury-related microRNA, while its role in traumatic brain injury remains indistinct. Herein, we explored the participation of miR-31 in traumatic brain injury. Traumatic brain injury model was established after traumatic neuron injury. Neurocytes were transfected with miR-31 mimic or inhibitor. Cell counting kit-8, lactate dehydrogenase assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, and western blot were applied to examine cell viability, lactate dehydrogenase releasing, apoptosis, and apoptosis-related protein. The binding between miR-31 and hypoxia-inducible factor-1A was verified by luciferase assay. Quantitative reverse transcription-PCR was used to detect the regulation of traumatic neuron injury or hypoxia-inducible factor-1A overexpression on vascular endothelial growth factor A level. The effects of hypoxia-inducible factor-1A or vascular endothelial growth factor A on neuronal cell injury were examined. Additionally, phosphatidylinositol 3kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway was also examined using western blot. Downregulation of miR-31 promoted traumatic neuron injury-induced neuronal cell injury, and its overexpression did the opposite. Hypoxia-inducible factor-1A acted as a downstream mRNA of miR-31 and its downregulation was involved in miR-31-regulated neuronal cell injury. Vascular endothelial growth factor A level was elevated by traumatic neuron injury or hypoxia-inducible factor-1A overexpression. Hypoxia-inducible factor-1A enhanced neuronal cell injury via promoting vascular endothelial growth factor A expression. Furthermore, miR-31/hypoxia-inducible factor-1A/vascular endothelial growth factor A regulated PI3K/AKT/mTOR pathway in neuronal cells. Our study demonstrated miR-31 inhibited neuronal cell apoptosis via regulating hypoxia-inducible factor-1A/vascular endothelial growth factor A axis.
PEG-PEI/siROCK2 inhibits Aβ42-induced microglial inflammation via NLRP3/caspase 1 pathway
Authors: Liu Yunyun , Zhang Han , Peng Anping , Cai Xiaodong , Wang YuZhou , Tang Ke , Wu Xiuqin , Liang Yanran , Wang Limin , Li Zhong
Published: November 2021

Objectives

There is an urgent need to develop therapeutic strategies to improve the treatment outcome of Alzheimer’s disease. The treatment strategy of gene therapy mediated by nanocarrier systems brings new hope for the treatment of Alzheimer’s disease. ROCK2 is involved in various pathological processes of Alzheimer’s disease and may be a potential target for the treatment of Alzheimer’s disease. Our previous study indicated that PEG-PEI/siROCK2 [polyethyleneglycol-polyethyleneimine deliver ROCK2-siRNA, (PPSR)] prevented Aβ42-induced neurotoxicity and showed a promising prospect for the treatment of Alzheimer’s disease. However, whether PPSR has an effect on the microglial inflammation in Alzheimer’s disease is still unclear.

Materials and methods

3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay was used to detect the cytotoxicity of PEG-PEI and PPSR in primary microglial cells. Real-time PCR and western blotting were used to assess the expression of ROCK2 and nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/caspase 1 pathway in primary microglial cells. ELISA assay was used to measure the effect of PPSR on attenuating the lipopolysaccharide (LPS) + Aβ-induced increase in IL-1β.

Results

PEG-PEI concentration less than 20 μg/ml and the N/P (molar ratio of PEG-PEI amino/siRNA phosphate) ratio of PPSR less than 50 showed no significant cytotoxicity in primary microglia cells. PPSR could effectively inhibit the expression of ROCK2 in primary microglial cells. A further study revealed that PPSR attenuates the LPS+Aβ-induced increase in IL-1β without affecting cell viability. In addition, we found that PPSR suppressed the Aβ-induced NLRP3/caspase 1 pathway in primary microglial cells.

Conclusion

PPSR inhibits Aβ42-induced microglial inflammation via NLRP3/caspase 1 pathway.
The effect of Iridoids effective fraction of Valeriana jatamansi Jones on movement function in rats after acute cord injury and the related mechanism
Authors: Xiong Deqi , Liu Hao , Pang Rizhao , Yan Zhiyong , Sun Nianyi , Liu Jiancheng , Zheng Jinqi , Zhu Jiali , Lu Jiachun , Wang Wenchun , Zhang Anren
Published: November 2021

Objectives

Spinal cord injury (SCI) is a disastrous central nervous system (CNS) disorder, which was intimately associated with oxidative stress. Studies have confirmed that Iridoids Effective Fraction of Valeriana jatamansi Jones (IEFV) can scavenge reactive oxygen species. This study aimed to confirm the efficacy of IEFV in ameliorating SCI.

Methods

For establish the SCI model, the Sprague-Dawley rats underwent a T10 laminectomy with transient violent oppression by aneurysm clip. Then, the rats received IEFV intragastrically for 8 consecutive weeks to evaluate the protective effect of IEFV on motor function, oxidative stress, inflammation and neurotrophic factors in SCI rats.

Results

Basso, Beattie and Bresnahan scores, hematoxylin and eosin (H&E) staining and transmission electron microscopy experiments found IEFV protected motor function and alleviated neuron damage. Meanwhile, IEFV treatment decreased the release of malondialdehyde, interleukin-6 (IL-6), cyclooxygenase-2 and tumor necrosis factor-α. Moreover, IEFV treatment elevated the expression levels of brain-derived neurotrophic factor and nerve growth factor of SCI rats. Finally, administration of IEFV significantly inhibited the expression of p-p65 and toll-like receptor 4 (TLR4).

Conclusions

This study suggests that IEFV could attenuate the oxidative stress and inflammatory response of the spinal cord after SCI, which was associated with inhibition of the TLR4/nuclear factor-kappaB signaling pathway.
Host life-history traits influence the distribution of prophages and the genes they carry
Authors: Pattenden Tyler , Eagles Christine , Wahl Lindi M.
Published: November 2021

Bacterial strains with a short minimal doubling time—‘fast-growing’ hosts—are more likely to contain prophages than their slow-growing counterparts. Pathogenic bacterial species are likewise more likely to carry prophages. We develop a bioinformatics pipeline to examine the distribution of prophages in fast- and slow-growing lysogens, and pathogenic and non-pathogenic lysogens, analysing both prophage length and gene content for each class. By fitting these results to a mathematical model of the evolutionary forces acting on prophages, we predict whether the observed differences can be attributed to different rates of lysogeny among the host classes, or other evolutionary pressures. We also test for significant differences in gene content among prophages, identifying genes that are preferentially lost or maintained in each class. We find that fast-growing hosts and pathogens have a greater fraction of full-length prophages, and our analysis predicts that induction rates are significantly reduced in slow-growing hosts and non-pathogenic hosts. Consistent with previous results, we find that several proteins involved in the packaging of new phage particles and lysis are preferentially lost in cryptic prophages.

This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.
Gene sharing among plasmids and chromosomes reveals barriers for antibiotic resistance gene transfer
Authors: Wang Yiqing , Batra Aditi , Schulenburg Hinrich , Dagan Tal
Published: November 2021

The emergence of antibiotic resistant bacteria is a major threat to modern medicine. Rapid adaptation to antibiotics is often mediated by the acquisition of plasmids carrying antibiotic resistance (ABR) genes. Nonetheless, the determinants of plasmid-mediated ABR gene transfer remain debated. Here, we show that the propensity of ABR gene transfer via plasmids is higher for accessory chromosomal ABR genes in comparison with core chromosomal ABR genes, regardless of the resistance mechanism. Analysing the pattern of ABR gene occurrence in the genomes of 2635 Enterobacteriaceae isolates, we find that 33% of the 416 ABR genes are shared between chromosomes and plasmids. Phylogenetic reconstruction of ABR genes occurring on both plasmids and chromosomes supports their evolution by lateral gene transfer. Furthermore, accessory ABR genes (encoded in less than 10% of the chromosomes) occur more abundantly in plasmids in comparison with core ABR genes (encoded in greater than or equal to 90% of the chromosomes). The pattern of ABR gene occurrence in plasmids and chromosomes is similar to that in the totalEscherichiagenome. Our results thus indicate that the previously recognized barriers for gene acquisition by lateral gene transfer apply also to ABR genes. We propose that the functional complexity of the underlying ABR mechanism is an important determinant of ABR gene transferability.

This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.
Intraspecific antagonism through viral toxin encoded by chronicSulfolobusspindle-shaped virus
Authors: DeWerff Samantha J. , Zhang Changyi , Schneider John , Whitaker Rachel J.
Published: November 2021

Virus–host interactions evolve along a symbiosis continuum from antagonism to mutualism. Long-term associations between virus and host, such as those in chronic infection, will select for traits that drive the interaction towards mutualism, especially when susceptible hosts are rare in the population. Virus–host mutualism has been demonstrated in thermophilic archaeal populations whereSulfolobusspindle-shaped viruses (SSVs) provide a competitive advantage to their hostSulfolobus islandicusby producing a toxin that kills uninfected strains. Here, we determine the genetic basis of this killing phenotype by identifying highly transcribed genes in cells that are chronically infected with a diversity of SSVs. We demonstrate that these genes alone confer growth inhibition by being expressed in uninfected cells via aSulfolobusexpression plasmid. Challenge of chronically infected strains with vector-expressed toxins revealed a nested network of cross-toxicity among divergent SSVs, with both broad and specific toxin efficacies. This suggests that competition between viruses and/or their hosts could maintain toxin diversity. We propose that competitive interactions among chronic viruses to promote their host fitness form the basis of virus–host mutualism.

This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.
Native American Ancestry and Pigmentation Allele Contributions to Skin Color in a Caribbean Population
Authors: Ang Khai C , Canfield Victor A , Foster Tiffany C , Harbaugh Thaddeus D , Early Kathryn A , Harter Rachel L , Reid Katherine P , Leong Shou Ling , Kawasawa Yuka I , Liu Dajiang J , Hawley John W , Cheng Keith C
Published: November 2021

Our interest in the genetic basis of skin color variation between populations led us to seek a Native American population with African admixture but low frequency of European light skin alleles. Analysis of 458 genomes from individuals residing in the Kalinago territory of the Commonwealth of Dominica showed approximately 55% Native American, 32% African, and 12% European ancestry, the highest Native American ancestry among Caribbean populations to date. Skin pigmentation ranged from 20 to 80 melanin units, averaging 46. Three albino individuals were determined to be homozygous for a causative multi-nucleotide polymorphismOCA2NW273KVcontained within a haplotype of African origin; its allele frequency was 0.03 and single allele effect size was -8 melanin units. Derived allele frequencies ofSLC24A5A111TandSLC45A2L374Fwere 0.14 and 0.06, with single allele effect sizes of -6 and -4, respectively. Native American ancestry by itself reduced pigmentation by more than 20 melanin units (range 24 - 29). The responsible hypopigmenting genetic variants remain to be identified, since none of the published polymorphisms predicted in prior literature to affect skin color in Native Americans caused detectable hypopigmentation in the Kalinago.
Prioritizing interventions for preventing COVID-19 outbreaks in military basic training
Authors: España Guido , Perkins T. Alex , Pollett Simon , Smith Morgan E. , Moore Sean M. , Kwon Paul O. , Hall Tara L. , Beagle Milford H. , Murray Clinton K. , Hakre Shilpa , Peel Sheila , Modjarrad Kayvon , Scott Paul T.
Published: November 2021

Like other congregate living settings, military basic training has been subject to outbreaks of COVID-19. We sought to identify improved strategies for preventing outbreaks in this setting using an agent-based model of a hypothetical cohort of trainees on a U.S. Army post. Our analysis revealed unique aspects of basic training that require customized approaches to outbreak prevention, which draws attention to the possibility that customized approaches may be necessary in other settings, too. In particular, we showed that introductions by trainers and support staff may be a major vulnerability, given that those individuals remain at risk of community exposure throughout the training period. We also found that increased testing of trainees upon arrival could actually increase the risk of outbreaks, given the potential for false-positive test results to lead to susceptible individuals becoming infected in group isolation and seeding outbreaks in training units upon release. Until an effective transmission-blocking vaccine is adopted at high coverage by individuals involved with basic training, need will persist for non-pharmaceutical interventions to prevent outbreaks in military basic training. Ongoing uncertainties about virus variants and breakthrough infections necessitate continued vigilance in this setting, even as vaccination coverage increases.

Significance Statement

COVID-19 has presented enormous disruptions to society. Militaries are not immune to these disruptions, with outbreaks in those settings posing threats to national security. We present a simulation model of COVID-19 outbreaks in a U.S. Army basic training setting to inform improved approaches to prevention there. Counterintuitively, we found that outbreak risk is driven more by virus introductions from trainers than the large number of trainees, and that outbreak risk is highly sensitive to false-positive results during entry testing. These findings suggest practical ways to improve prevention of COVID-19 outbreaks in basic training and, as a result, maintain the flow of new soldiers into the military. This work highlights the need for bespoke modeling to inform prevention in diverse institutional settings.
Understanding the burden and mitigating risks in the utilisation of the Emergency Medical Services in the management of community mental health emergencies
Authors: Howard Ian , Castle Nicholas , Shaikh Loua Al , Owen Robert
Published: November 2021

Introduction

Mental health disorders are highly prevalent globally with access to appropriate care oftentimes problematic. The Emergency Medical Services (EMS) have been suggested as a potential solution to improve access, however, it is unclear whether these services provide the most appropriate response with respect to the needs of patients experiencing a mental health emergency.

Methods

A multi-method study was conducted to assess the current burden and potential risks associated with the transportation of patients experiencing a mental health emergency by EMS. Part 1 utilised a cross-sectional study of routinely collected clinical data for the period January 2018 to December 2019. Part 2 employed a systematic risk identification methodology focused on identifying the hazards associated with the transportation of this patient cohort, to identify key action plans towards mitigating their occurrence.

Results

Patients experiencing a mental health emergency were transported at an average rate of 11.96 per 1000 transports. Approximately 7% were administered prehospital sedation, with Ketamine administered as the most common sedative. Altogether, 50 potential hazards were identified involving the transportation of patients experiencing a mental health emergency. The Patient Assessment subprocess contained the most potential hazards/failure points (n=13). Risks categorized as occasional (n=33) and moderate (n=16) made up the majority.

Conclusion

The burden of mental health emergencies on EMS is considerable, with the potential for several significant risks. Despite this, there was unequal focus on the development of care pathways and clinical guidance for this patient cohort compared with the more “traditional” case types serviced by EMS. Consequently, we identified several strategic-level action plans to mitigate these hazards and improve the delivery of care for these patients in the community.
Random clonal expansion as a limiting factor in transplantable in vivo CRISPR/Cas9 screens
Authors: Lee Tet Woo , Hunter Francis W. , Wilson William R. , Jamieson Stephen M.F.
Published: November 2021

Transplantable in vivo CRISPR/Cas9 knockout screens, in which cells are transduced in vitro and inoculated into mice to form tumours in vivo, offer the opportunity to evaluate gene function in a cancer model that incorporates the multicellular interactions of the tumour microenvironment. In this study, we sought to develop a head and neck squamous cell carcinoma (HNSCC) tumour xenograft model for whole-genome screens that could maintain high gRNA representation during tumour initiation and progression. To achieve this, we sought early-passage HNSCC cell lines with a high frequency of tumour initiation-cells, and identified the pseudodiploid UT-SCC-54C line as a suitable model from 23 HNSCC lines tested based on a low tumourigenic dose for 50% takes (TD50) of 1100 cells in NSG mice. On transduction with the GeCKOv2 whole-genome gRNA library (119,461 unique gRNAs), high (80-95%) gRNA representation was maintained in early (up to 14 d) UT-SCC-54C tumours in NSG mice, but not in UT-SCC-74B tumours (TD50=9200). However, loss of gRNA representation was observed in UT-SCC-54C tumours following growth for 38-43 days, which correlated with a large increase in bias among gRNA read counts due to stochastic expansion of clones in the tumours. Applying binomial thinning simulations revealed that the UT-SCC-54C model would have 40-90% statistical power to detect drug sensitivity genes with log2 fold change effect sizes of 1-2 in early tumours with gRNA libraries of up to 10,000 gRNAs and modest group sizes of 5 tumours. In large tumours, this model would have had 45% power to detect log2 fold change effect sizes of 2-3 with libraries of 2,000 gRNAs and 14 tumours per group. Based on our findings, we conclude that gRNA library size, sample size and tumour size are all parameters that can be individually optimised to ensure transplantable in vivo CRISPR screens can successfully evaluate gene function.
The gradient model of brain organization in decisions involving ‘empathy for pain’
Authors: Labek Karin , Sittenberger Elisa , Kienhöfer Valerie , Rabl Luna , Messina Irene , Schurz Matthias , Stingl Julia C. , Viviani Roberto
Published: November 2021

Influential models of cortical organization propose a close relationship between heteromodal association areas and highly connected hubs in the default mode network. The ‘gradient model’ of cortical organization proposes a close relationship between these areas and highly connected hubs in the default mode network, a set of cortical areas deactivated by demanding tasks. Here, we used a decision-making task and representational similarity analysis with classic ‘empathy for pain’ stimuli to probe the relationship between high-level representations of imminent pain in others and these areas. High-level representations were co-localized with task deactivations or the transitions from activations to deactivations. These loci belonged to two groups: those that loaded on the high end of the principal cortical gradient and were associated by meta-analytic decoding with the default mode network, and those that appeared to accompany functional repurposing of somatosensory cortex in the presence of visual stimuli. In contrast to the nonspecific meta-analytic decoding of these loci, low-level representations, such as those of body parts involved in pain or of pain itself, were decoded with matching topics terms. These findings suggest that task deactivations may set out cortical areas that host high-level representations. We anticipate that an increased understanding of the cortical correlates of high-level representations may improve neurobiological models of social interactions and psychopathology.