bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences and Needs of Caregivers of Adult Patients With Hematologic Malignancies During Treatment
Authors: Husted Nielsen Iben , Piil Karin , Grønbæk Kirsten , Kjeldsen Lars , Jarden Mary
Published: January 2022

Background

Family caregivers play a vital role in providing care and support for patients with life-threatening hematologic diseases. Extensive patient care needs and long-term treatment trajectories can negatively affect the health of caregivers. Despite the importance of supporting caregivers, few studies examine family caregivers’ experiences and support needs during treatment.

Objective

To explore the role, experiences, and needs of family caregivers of patients with hematologic malignancies during treatment.

Methods

An exploratory longitudinal qualitative study using serial semistructured interviews with caregivers of hematologic patients was carried out. Data were analyzed using thematic analysis.

Results

A sample of 16 caregivers completed 47 interviews. Three themes and 2 subthemes were identified: (1) committing to an unconditional mission while adjusting to a changeable situation: developing resilience over time; (2) being an invisible and inseparable sufferer: cultivating hope one day at a time; and (3) balancing between sacrificing one’s own needs and self-care.

Conclusions

During treatment, caregivers face long-term psychological and physical distress, social isolation, and loneliness due to the extended life-threatening situation imposing shifting challenges and needs. Future research should explore the concept of social support in caregiver resilience and investigate psychosocial interventions in hematologic caregivers.

Implications for Practice

Healthcare professionals should address caregiver needs throughout the patient’s treatment and provide new supportive initiatives to lessen the burden of care in hematologic caregivers. Facilitating peer support and deploying a family-oriented approach considering the patient-caregiver dyad as a subject for care have implications for clinical nursing practice.
Effects of Clinical Nurse Educator Professional Role Development
Authors: Dagg Connie C. , Schubert Carolyn , Beckett Cynthia , Fitzgerald Elizabeth A.
Published: January 2022

Centralization of clinical nurse educators (CNEs) from medical-surgical and critical care in a rural Midwestern hospital created role confusion and poor role outcomes. An evidence-based quality improvement project was developed to integrate the Association of Nursing Professional Development’s transition to practice fellowship and practice model. Outcomes were focused on CNE self-assessed competency and three nurse-sensitive quality outcomes. Results were mixed but support that CNEs influenced patient quality outcomes and improved their self-assessed competency.
Risk Factors for Ankle Fractures in Asian Adolescents Seen in a Pediatric Emergency Department
Authors: Cher Wenqi , Quek Samuel Enci , Badron Junaidah , Feng Jasmine , Ong Gene Yong-Kwang , Lee Khai Pin , Chong Shu-Ling
Published: January 2022

Objectives

Pediatric ankle injuries remain one of the most common presenting complaints to the pediatric emergency department (PED). In this study, we aimed to describe risk factors associated with simple ankle fractures and ankle fractures that require surgery, among adolescents presenting to the PED with ankle injuries.

Methods

We analyzed a retrospective cohort study of adolescents 12 to 16 years old who presented to our PED with an acute ankle injury and received an ankle radiograph from November 1, 2016, to October 31, 2017. Demographic, anthropometric variables, physical examination findings including those of the Ottawa Ankle Rules were obtained. We recorded any surgical interventions required, as well as follow-up and to return to physical activity.

Results

Five hundred fifty-six cases of adolescent ankle injuries were reviewed, of which 109 adolescents had ankle fractures, whereas 19 had ankle fractures requiring surgery. Sports-related injuries remained the most common cause of ankle fractures. Age (adjusted odds ratio [aOR], 0.69; 95% confidence interval [CI], 0.56–0.83; P < 0.001), male sex (aOR, 2.12; 95% CI, 1.34–3.35; P < 0.001), clinical findings of tenderness over the lateral malleolus (aOR, 3.13; 95% CI, 1.74–5.64; P < 0.001) or medial malleolus (aOR, 3.55; 95% CI, 2.18–5.78; P < 0.001), and inability to walk (aOR, 3.09; 95% CI, 1.95–4.91; P < 0.001) were significant independent risk factors for ankle fractures.

Patients with a weight more than 90th centile for age were at greater risk of ankle fractures requiring surgery (aOR, 2.64; 95% CI, 1.05–6.64; P = 0.04).

Conclusions

We found that younger age, male sex, and clinical findings in the Ottawa Ankle Rules correlated well with predicting ankle fractures and are well suited for application in the Southeast Asian population. Weight greater than the 90th percentile for age was a significant risk factor for ankle fractures requiring surgery.
Reducing Phlebotomy, Length of Stay, Cost
Authors: Rinnan Jean Marie A. , Latreille Jacob , Nanassy Autumn D. , Gaughan John , Lindholm Erika B. , Grewal Harsh , Kassutto Zach , Arthur L. Grier
Published: January 2022

Objectives

Blunt abdominal trauma (BAT) is a leading cause of morbidity in children with higher hemodynamic stabilities when compared with adults. Pediatric patients with BAT can often be managed without surgical interventions; however, laboratory testing is often recommended. Yet, laboratory testing can be costly, and current literature has not identified appropriate pathways or specific tests necessary to detect intra-abdominal injury after BAT. Therefore, the present study evaluated a proposed laboratory testing pathway to determine if it safely reduced draws of complete blood counts, coagulation studies, urinalysis, comprehensive metabolic panels, amylase and lipase levels orders, emergency department (ED) length of stay, and cost in pediatric BAT patients.

Methods

A retrospective review of levels I, II, and III BAT pediatric patients (n = 329) was performed from 2015 to 2018 at our level I, pediatric trauma center. Patients were then grouped based on pre-post pathway, and differences were calculated using univariate analyses.

Results

After implementation of the pathway, there was a significant decrease in the number of complete blood counts, coagulation studies, urinalysis, comprehensive metabolic panels, amylase, and lipase levels orders (P < 0.05). Postpathway patients had lower average ED lengths of stay and testing costs compared with the pre pathway patients (P < 0.05). There was no increase in rates of return to the ED within 30 days, missed injuries, or readmissions of patients to the ED.

Conclusions

Results displayed that the adoption of a laboratory testing pathway for BAT patients reduced the number of laboratory tests, ED length of stay, and associated costs pediatric patients without impacting quality care.
Selection, Confounding, and Attrition Biases in Randomized Controlled Trials of Rehabilitation Interventions
Authors: Armijo-Olivo Susan , de Oliveira-Souza Ana Izabela Sobral , Mohamad Norazlin , de Castro Carletti Ester Moreira , Fuentes Jorge , Ballenberger Nikolaus
Published: January 2022

A thorough knowledge of biases in intervention studies and how they influence study results is essential for the practice of evidence-based medicine. The objective of this review was to provide a basic knowledge and understanding of the concept of biases and associated influence of these biases on treatment effects, focusing on the area of rehabilitation research. This article provides a description of selection biases, confounding, and attrition biases. In addition, useful recommendations are provided to identify, avoid, or control these biases when designing and conducting rehabilitation trials. The literature selected for this review was obtained mainly by compiling the information from several reviews looking at biases in rehabilitation. In addition, separate searches by biases and looking at reference lists of selected studies as well as using Scopus forward citation for relevant references were used. If not addressed appropriately, biases related to intervention research are a threat to internal validity and consequently to external validity. By addressing these biases, ensuring appropriate randomization, allocation concealment, appropriate retention techniques to avoid dropouts, appropriate study design and statistical analysis, among others, will generate more accurate treatment effects. Based on their impact on clinical results, a proper understanding of these concepts is central for researchers, rehabilitation clinicians, and other stakeholders working on this field.
Effects of Stroke Lesions and Timing of Rehabilitation on the Compensatory Movement Patterns During Stroke Recovery
Authors: Lee Kyoung-hee , Jeong Eun-Hwa , Joa Kyung-Lim
Published: January 2022

Objectives

The aims of this study were to distinguish between behavioral compensation and behavioral recovery and to determine the role of stroke lesions and the optimal timing of rehabilitation in true recovery.

Design

Single pellet reaching test has been performed to analyze both quantitative and qualitative measures of forelimb function in a stroke animal model with lesions in the motor cortex, somatosensory cortex, or sensorimotor cortex. The four gestures of compensatory movement patterns that comprised a reach were head lift, limb withdrawal, pellet chasing, and phantom grasp.

Results

Functional recovery improved in all the stroke groups after rehabilitation (P < 0.001). However, the compensatory movement patterns of the motor cortex and somatosensory cortex stroke groups initially increased and subsequently decreased (P = 0.0054), whereas those of the sensorimotor cortex stroke group increased and persisted (P = 0.0063). In the sensorimotor cortex stroke group, compensatory movement patterns significantly decreased when training was initiated 5 and 14 days after stroke (P = 0.0083, P = 0.0226, respectively), while they increased and persisted when training was initiated 1 day after stroke.

Conclusions

These findings suggest that true recovery by task-specific training after stroke depends, probably, on the lesion size and the timing of rehabilitation.
From Histoanatomy to Sonography in Myofascial Pain Syndrome
Authors: Ricci Vincenzo , Ricci Costantino , Gervasoni Fabrizio , Cocco Giulio , Andreoli Arnaldo , Özçakar Levent
Published: January 2022

Myofascial pain is a common clinical condition, whereby accurate physical examination is usually considered as the cornerstone to identify/diagnose the “trigger point complex,” that is, the characteristic finding of this syndrome. Considering the emerging role of ultrasound examination as the natural extension of physical assessment for musculoskeletal disorders, we briefly revise the histological/anatomical features of trigger points and propose a standardized, multistep sonographic approach to myofascial pain. We also imply that the integrated clinical-ultrasound evaluation could be considered as a potential tool to discriminate different phases/subsets of this challenging pathology.
The Prevalence and Incidence of Irritable Bowel Syndrome and Inflammatory Bowel Disease in Depression and Bipolar Disorder: A Systematic Review and Meta-Analysis
Authors: Nikolova Viktoriya L. , Pelton Lucy , Moulton Calum D. , Zorzato Daniele , Cleare Anthony J. , Young Allan H. , Stone James M.
Published: January 2022

Objective

The increased prevalence and incidence of affective disorders among patients with gastrointestinal disease have been well established. However, few studies have investigated the inverse relationship. We aimed to identify all pieces of evidence of the prevalence and incidence of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) in people with depression and bipolar disorder.

Methods

We conducted a systematic review of studies reporting the association between affective disorders (exposure) and IBS or IBD (outcome) in adults. Evidence was evaluated for quality using Joanna Briggs Institute Critical Appraisal tools. Where suitable data were available, meta-analyses were performed.

Results

We identified 18 studies that met the selection criteria, of which 11 provided data on IBS, 5 on IBD, and 2 on both. Overall, people with depression were significantly more likely to have comorbid IBS (risk ratio = 2.42, 95% confidence interval = 1.98–2.96) and to develop new-onset IBS (risk ratio = 1.90, 95% confidence interval = 1.41–2.56) compared with people without depression. They were also more likely to have and develop IBD, and among patients with IBD, significantly increased rates of depression were observed as early as 5 years before diagnosis. Bipolar disorder was not consistently associated with risk of either condition.

Conclusions

People with depression are at an increased risk of both having and developing lower gastrointestinal disorders. These findings have important implications for how we understand, manage, and prevent this comorbidity in clinical practice. Further studies are needed to improve our understanding of the relationship between bipolar disorder and bowel disease as well as the role of psychotropic medication, particularly selective serotonin reuptake inhibitors.
Psychological Distress During Pregnancy and the Development of Pregnancy-Induced Hypertension: A Prospective Study
Authors: Pop Victor J.M. , Boekhorst Myrthe G.B.M. , Deneer Rianne , Oei Guid , Endendijk Joyce J. , Kop Willem J.
Published: January 2022

Objective

Pregnancy-induced hypertension (PIH) is associated with serious complications in both the mother and the unborn child. We examined the possible association between trajectories of maternal psychological distress symptoms and PIH separately in primiparous and multiparous women.

Methods

Pregnancy-specific negative affect (P-NA) and depressive symptoms were assessed prospectively at each trimester using the Tilburg Pregnancy Distress Scale pregnancy negative affect subscale (P-NA) and the Edinburgh Depression Scale (EDS). Data on PIH were collected from medical records. Growth mixture modeling analysis was used to identify trajectories of P-NA and EDS. The independent role of P-NA and EDS symptom trajectories on developing PIH was examined using multivariate logistic regression models.

Results

One hundred (7.6%) women developed PIH and were compared with 1219 women without hypertension or other complications during pregnancy. Three P-NA trajectories were identified: low stable (reference group; 90%), decreasing (5.2%), and increasing (4.8%). The latter two classes showed persistently and significantly higher P-NA symptoms during pregnancy compared with the reference group. In multiparous women, high P-NA scores (belonging to classes 2 and 3) were related to PIH (odds ratio [OR] = 6.91, 95% confidence interval [CI] = 2.26–21.2), independent of body mass index (OR = 1.17, 95% CI = 1.06–1.27) and previous PIH (OR = 14.82, 95% CI = 6.01–32.7). No associations between P-NA and PIH were found in primiparous women. EDS trajectories were not related to PIH in both primiparous and multiparous women.

Conclusions

In multiparous women, persistently high levels of P-NA symptoms but not depressive symptoms were independently associated with development of PIH.
Is Elective Nighttime Operation Associated With Adverse Outcomes? Analysis in Immediate Tissue Expander–Based Breast Reconstruction
Authors: Kim Woo-Ju , Pyon Jai-Kyong , Mun Goo-Hyun , Bang Sa-Ik , Jeon Byung-Joon , Lee Kyeong-Tae
Published: January 2022

Background

Despite the long-standing presumption that nighttime surgery could affect adverse outcomes, its association independent of patient’s general condition and disease severity remains unclear. We hypothesized that conducting elective surgery for subjects with good physical status at nighttime was not associated with increased risks of postoperative complications and aimed to examine it in tissue-expander-insertion (TEI) operation for breast reconstruction.

Method

Patients who underwent immediate unilateral TEI-based breast reconstruction between 2014 and 2019 were enrolled. They were categorized into 3 groups based on the starting time of the TEI operation: 8 am to 6 pm (group 1), 6 pm to 8 pm (group 2), and after 8 pm (group 3). The postoperative complication rates were compared among the groups. The independent associations of each variable, including the operation starting time and adverse outcomes, were analyzed.

Results

In total, 1458 patients were analyzed, including 970 in group 1, 358 in group 2, and 130 in group 3. The groups showed similar baseline characteristics regarding comorbidities and the American Society of Anesthesiologists classification. Compared with group 1, group 3 was associated with significantly increased rates of overall complications including infection, reoperation, and premature removal of the tissue expander. These differences retained influences in the multivariable analyses. Group 3 showed a significantly longer hospitalization period than the other 2 groups. The complication rates did not differ between groups 1 and 2.

Conclusions

Conducting TEI operation at nighttime seems to be associated with increased risks of adverse postoperative outcomes compared with conducting it during regular working hours.
Are Operating Rooms With Laminar Airflow a Risk for Inadvertent Perioperative Hypothermia During Ureterorenoscopic Lithotripsy Under Spinal Anesthesia? A Prospective Randomized Clinical Trial
Authors: Dagli Recai , Bağbancı Muhammet Şahin , Dadalı Mümtaz , Erşekerci Erol
Published: January 2022

Objectives

Inadvertent perioperative hypothermia (IPH), defined as a core temperature <36°C, is common during a surgical procedure and is associated with high morbidity and mortality. Laminar (LAS) and conventional airflow systems (CAS) are used frequently for clean microenvironmental surgical areas in operating rooms. In LAS, the cold airflow is directed toward the patient, unlike CAS. Does this airflow in LAS cause heat loss from the patient by convection more than CAS? We aimed to compare the IPH frequencies of these airflow systems on patients who underwent ureterorenoscopic lithotripsy (ureterorenoscopic surgery) under spinal anesthesia.

Methods

The study was a prospective, parallel-group, randomized trial. A total of 246 volunteers were included in the study and divided into group LAS (n = 123) and group CAS (n = 123). Randomization of patients was performed using the closed-envelope method (as 1:1).

The tympanic membrane temperature of patients was measured before spinal anesthesia (T
0) and then every 15 minutes (Tn
) during the procedure. The IPH ratio and the change of the tympanic temperatures (Δ
T
) were recorded (clinical trial number: IRCT20180324039145N5).

Results

In total, there were no statistical differences between the IPH ratios of group LAS and group CAS (61.2% [71 of 116] versus 49.6% [57 of 115], respectively; P = 0.075). The IPH ratio was 55.4% (128 of 231). The tympanic temperatures of patients decreased about 0.64°C (0.45°C) at the 30th minute. In both groups, Δ30 was similar (0.62; 95% confidence interval, 0.52–0.72 [P = 0.65]; 95% confidence interval, 0.55–0.74 [P = 0.236], respectively).

Conclusions

The risk for IPH of both LAS and CAS in the operating room is similar during ureterorenoscopic surgery.
Fibroblast Activation Protein Inhibitor Imaging and Therapy in a Patient With Multiple Endocrine Neoplasia Type 2A Syndrome
Authors: Barashki Somaye , Divband Ghasemali , Askari Emran , Amini Hamidreza , Aryana Kamran
Published: January 2022

A patient with multiple endocrine neoplasia type 2A syndrome who had exhausted several surgeries and radiotherapy was referred to nuclear medicine department for theranostic approaches. [68Ga]-DOTATATE PET/CT and [131I]I-mIBG SPECT/CT were performed, but the degree of uptake was insufficient for using the treatment companion of these tracers. Finally, 1 year later, [68Ga]-FAPI-46 PET/CT showed progressive disease with metastases to the lung, liver, bone, and lymph nodes with intense [68Ga]-FAPI-46 uptake. Treatment with [177Lu]Lu-FAPI-46 was done, and the patient tolerated treatment and showed evidence of clinical improvement following therapy.
68Ga-PSMA PET/CT Scan Leading to Diagnosis of PSMA-Positive Rectal Adenocarcinoma in a Patient With Prostate Cancer
Authors: Norouzi Ghazal , Rezaei Alireza , Adinehpour Zohreh , Amini Hamidreza , Vali Reza
Published: January 2022

A 59-year-old prostate cancer patient, status post radical prostatectomy, was referred to our department for restaging with 68Ga–prostate-specific membrane antigen (PSMA) PET/CT scan. Aside multiple metastatic lesions involving pelvic lymph nodes as well as the right femoral trochanter, a PSMA-positive rectal wall thickening was detected. Colonoscopy correlation and tissue diagnosis, recommended to rule out accompanying primary malignancy, confirmed the presence of rectal adenocarcinoma. This case signifies the importance of requesting pathological correlation for unexplained PSMA-positive lesions, emphasizing the potential role PSMA ligands may play in detecting occult second primary malignancies, especially synchronous/metachronous colorectal cancers.
Primary Adrenal Sarcomatoid Carcinoma Detected by 18F-FDG PET/CT
Authors: Zhang Jinxin , Gong Weidong , Zhang Wenwen , Zhang Chunyin , Zhang Guoxu
Published: January 2022

Adrenal sarcomatoid carcinoma is extremely rare. A 53-year-old man was admitted to our hospital due to pain in the upper right abdomen for 1 month. Abdominal CT revealed a huge mass in the right adrenal gland, and a malignancy was suspected. 18F-FDG PET/CT showed a mass in the right adrenal gland with intense FDG uptake. Finally, postoperative pathology confirmed the diagnosis of adrenal sarcomatoid carcinoma.
First-in-Human Intrathoracic Implantation of Multidrug-Eluting Microdevices for In Situ Chemotherapeutic Sensitivity Testing as Proof of Concept in Nonsmall Cell Lung Cancer
Authors: Tsai Lillian L. , Phillips William W. , Hung Yin P. , Dominas Christine , Deans Kyle , Ahn Sebastian , Ferland Benjamin , Weiss Kathleen , Lanuti Michael , Auchincloss Hugh , Schumacher Lana , Jonas Oliver , Colson Yolonda L.
Published: January 2022

Objective:

To evaluate the safety and feasibility of implantation and retrieval of a novel implantable microdevice (IMD) in NSCLC patients undergoing operative resection.

Background:

Adjuvant therapy has limited impact on postsurgical outcomes in NSCLC due to the inability to predict optimal treatment regimens.

Methods:

An IMD measuring 6.5 mm by 0.7 mm, containing micro-reservoirs allowing for high-throughput localized drug delivery, was developed and loaded with 12 chemotherapeutic agents. Five patients with peripheral lung lesions larger than 1.0 cm were enrolled in this phase 1 clinical study. IMDs were inserted into tumors intraoperatively under direct vision, removed with the resected specimen, and retrieved in pathology. Surrounding tissues were sectioned, stained, and analyzed for tissue drug response to the IMD-delivered microdoses of these agents by a variety of pharmacodynamic markers.

Results:

A total of 14 IMDs were implanted intraoperatively with 13 (93%) successfully retrieved. After technique refinement, IMDs were reliably inserted and retrieved in open, Video-Assisted Thoracoscopic Surgery, and robotic cases. No severe adverse reactions were observed. The one retained IMD has remained in place without movement or any adverse effects. Analysis of patient blood revealed no detection of chemotherapeutic agents. We observed differential sensitivities of patient tumors to the drugs on the IMD.

Conclusions:

A multi-drug IMD can be safely inserted and retrieved into lung tumors during a variety of surgical approaches. Future studies will encompass preoperative placement to better examine specific tumor responsiveness to therapeutic agents, allowing clinicians to tailor treatment regimens to the microenvironment of each patient.
Advanced bleeding control in combat casualty care: An international, expert-based Delphi consensus
Authors: Vrancken Suzanne M. , Borger van der Burg Boudewijn L.S. , DuBose Joseph J. , Glaser Jacob J. , Hörer Tal M. , Hoencamp Rigo
Published: January 2022

BACKGROUND

Hemorrhage from truncal and junctional injuries is responsible for the vast majority of potentially survivable deaths in combat casualties, causing most of its fatalities in the prehospital arena. Optimizing the deployment of the advanced bleeding control modalities required for the management of these injuries is essential to improve the survival of severely injured casualties. This study aimed to establish consensus on the optimal use and implementation of advanced bleeding control modalities in combat casualty care.

METHODS

A Delphi method consisting of three rounds was used. An international expert panel of military physicians was selected by the researchers to complete the Delphi surveys. Consensus was reached if 70% or greater of respondents agreed and if 70% or greater responded.

RESULTS

Thirty-two experts from 10 different nations commenced the process and reached consensus on which bleeding control modalities should be part of the standard equipment, that these modalities should be available at all levels of care, that only trained physicians should be allowed to apply invasive bleeding control modalities, but all medical and nonmedical personnel should be allowed to apply noninvasive bleeding control modalities, and on the training requirements for providers. Consensus was also reached on the necessity of international registries and guidelines, and on certain indications and contraindications for resuscitative endovascular balloon occlusion of the aorta (REBOA) in military environments. No consensus was reached on the role of a wound clamp in military settings and the indications for REBOA in patients with chest trauma, penetrating axillary injury or penetrating neck injury in combination with thoracoabdominal injuries.

CONCLUSION

Consensus was reached on the contents of a standard bleeding control toolbox, where it should be available, providers and training requirements, international registries and guidelines, and potential indications for REBOA in military environments.
Influence of Calcineurin Inhibitor Choice on Outcomes in Kidney Transplant Recipients Aged ≥60 Y: A Collaborative Transplant Study Report
Authors: Echterdiek Fabian , Döhler Bernd , Latus Joerg , Schwenger Vedat , Süsal Caner
Published: January 2022

Background.

Patients aged ≥60 y represent the fastest growing population among kidney transplant recipients and waitlist patients. They show an elevated infection risk and are frequently transplanted with multiple human leukocyte antigen mismatches. Whether the choice of calcineurin inhibitor influences graft survival, mortality, or key secondary outcomes such as infections in this vulnerable recipient population is unknown.

Methods.

A total of 31 177 kidney transplants from deceased donors performed between 2000 and 2019 at European centers and reported to the Collaborative Transplant Study were analyzed using multivariable Cox and logistic regression analyses. All recipients were ≥60 y old and received tacrolimus (Tac) or cyclosporine A on an intention-to-treat basis, combined with mycophenolic acid or azathioprine plus/minus steroids.

Results.

The risk of 3-y death-censored graft loss and patient mortality did not differ significantly between Tac- and cyclosporine A-treated patients (hazard ratio 0.98 and 0.95, P = 0.74 and 0.20, respectively). No difference was found in the overall risk of hospitalization for infection (hazard ratio = 0.95, P = 0.19); however, a lower incidence of rejection treatment (hazard ratio = 0.81, P < 0.001) was observed in Tac-treated patients. Assessment of pathogen-specific hospitalizations revealed no difference in the risk of hospitalization due to bacterial infection (odds ratio = 1.00, P = 0.96), but a significantly higher risk of hospitalization due to human polyomavirus infection was found among Tac-treated patients (odds ratio = 2.45, P = 0.002). The incidence of de novo diabetes was higher for Tac-based immunosuppression (odds ratio = 1.79, P < 0.001).

Conclusions.

Calcineurin inhibitor selection has no significant influence on death-censored graft survival, mortality, and overall infection risk in ≥60-y-old kidney transplant recipients.
Neuropathology and epilepsy surgery
Authors: Hoffmann Lucas , Blümcke Ingmar
Published: January 2022

Purpose of review

Neurosurgical treatment of patients suffering from drug-resistant focal epilepsy is recognized as a successful, yet underutilized medical treatment option. By searching PubMed for articles published between January 2020 and September 2021 with the broad search terms ‘neuropathology’ AND ‘epilepsy surgery’, this review highlights the active field of etiology-based epilepsy research in human tissue.

Recent findings

All papers addressing the most common epileptogenic human brain disease entities, i.e. focal cortical dysplasia (FCD), brain tumors or hippocampal sclerosis, and written in English language were eligible for our review. We can conclude from this review that etiology-based studies are of foremost interest for (1) the development of prediction models for postsurgical seizure outcome; (2) decipher genetic and molecular alterations to better define disease entities and underlying molecular pathomechanisms, and (3) the translation of human tissue-derived biomarker into clinically useful diagnostics or novel therapeutic targets in the near future.

Highlighting FCD brain somatic gain-of-function variants in mammalian target of Rapamycin are a leading pathway to better classify FCD. An integrated genotype-phenotype analysis enables to classify the broad spectrum of low-grade and epilepsy-associated brain tumors. Further DNA-methylation-based disease classification will increase the mechanistic understanding and diagnostic precision of difficult to classify pathologies in the future.
Does pollen limitation limit plant ranges? Evidence and implications
Authors: Dawson-Glass Emma , Hargreaves Anna L.
Published: January 2022

Sexual reproduction often declines towards range edges, reducing fitness, dispersal and adaptive potential. For plants, sexual reproduction is frequently limited by inadequate pollination. While case studies show that pollen limitation can limit plant distributions, the extent to which pollination commonly declines towards plant range edges is unknown. Here, we use global databases of pollen-supplementation experiments and plant occurrence data to test whether pollen limitation increases towards plant range edges, using a phylogenetically controlled meta-analysis. While there was significant pollen limitation across studies, we found little evidence that pollen limitation increases towards plant range edges. Pollen limitation was not stronger towards the tropics, nor at species' equatorward versus poleward range limits. Meta-analysis results are consistent with results from targeted experiments, in which pollen limitation increased significantly towards only 14% of 14 plant range edges, suggesting that pollination contributes to range limits less often than do other interactions. Together, these results suggest pollination is one of the rich variety of potential ecological factors that can contribute to range limits, rather than a generally important constraint on plant distributions.

This article is part of the theme issue ‘Species’ ranges in the face of changing environments (part I)’.
Pseudomonas canavaninivorans sp. nov., isolated from bean rhizosphere
Authors: Hauth Franziskus , Buck Hiltrun , Hartig Jörg S.
Published: January 2022

A novel canavanine-degrading bacterium, strain HB002T, was isolated from rhizosphere soil of a catch crop field collected from the island of Reichenau in Konstanz, Germany, and characterized by using polyphasic taxonomy. The facultative aerobe, rod-shaped, Gram-stain-negative bacterium was oxidase- and catalase-positive. The isolate was able to grow on canavanine as a sole carbon and nitrogen source. Results of phylogenetic analysis based on 16S rRNA gene sequences revealed highest similarities to

Pseudomonas bijieensis

(L22-9T, 99.93 %),

Pseudomonas brassicacearum

subsp.

neoaurantiaca

(ATCC 49054T, 99.76 %),

Pseudomonas brassicacearum

subsp.

brassicacearum

(DBK 11T, 99.63 %),

Pseudomonas thivervalensis

(DSM 13194T, 99.51 %),

Pseudomonas kilonensis

(DSM 13647T, 99.39 %) and

Pseudomonas corrugata

(ATCC29736T, 99.39 %). Marker gene analysis placed the strain in the intrageneric group of

Pseudomonas fluorescens

, subgroup

P. corrugata

. In silico DNA–DNA hybridization and average nucleotide identity values were both under the recommended thresholds for species delineation. The predominant fatty acids of strain HB002T were C16 : 0, C17 : 0 cyclo ω7c and C18 : 1 ω7c. The major respiratory quinone was Q9, followed by Q8 and minor components of Q7 and Q10. Results from the phenotypic characterization showd the strain's inability to hydrolyse gelatin and to assimilate N-acetyl glucosamide and a positive enzymatic activity of acid phosphatase and naphthol-AS-BI phosphohydrolase that distinguish this strain from closely related type strains. Taken together, these results show that strain HB002T represents a novel species in the genus

Pseudomonas

, for which the name Pseudomonas canavaninivorans sp. nov. is proposed. The type strain is HB002T (=DSM 112525T=LMG 32336T).
Mycoplasma miroungirhinis sp. nov. and Mycoplasma miroungigenitalium sp. nov., isolated from northern elephant seals (Mirounga angustirostris), Mycoplasma phocoenae sp. nov., isolated from harbour porpoise (Phocoena phocoena), and Mycoplasma phocoeninasale sp. nov., isolated from harbour porpoise and California sea lions (Zalophus californianus)
Authors: Volokhov Dmitriy V. , Furtak Vyacheslav A. , Blom Jochen , Zagorodnyaya Tatiana A. , Gao Yamei , Gulland Frances M.
Published: January 2022

Seven novel independent strains of

Mycoplasma

species were isolated from northern elephant seals (ES2806-NAST, ES2806-GENT, ES3157-GEN-MYC and ES3225-GEN-MYC), a harbour porpoise (C264-GENT and C264-NAST), and a California sea lion (CSL7498). These strains were phenotypically and genetically characterized and compared to the known

Mycoplasma

species. Four strains (C264-GENT, C264-NAST, CSL7498 and ES2806-NAST) hydrolysed arginine but not urea and did not produce acid from carbohydrates. Strains ES2806-GENT, ES3157-GEN-MYC and ES3225-GEN-MYC did not produced acid from carbohydrates and did not hydrolyse arginine or urea; hence, it is assumed that organic acids are used as the energy source for them. All were isolated and propagated in ambient air supplemented with 5±1 % CO2 at +35–37 °C using either SP4 or PPLO medium. Colonies on solid medium showed a typical fried-egg appearance and transmission electron microscopy revealed a typical mycoplasma cellular morphology. The complete genomes were sequenced for all type strains. Average nucleotide and amino acid identity analyses showed that these novel strains were distant from the phylogenetically closely related

Mycoplasma

species. Based on these data, we propose four novel species of the genus

Mycoplasma

, for which the name Mycoplasma miroungirhinis sp. nov. is proposed with the type strain ES2806-NAST (=NCTC 14430T=DSM 110945T), Mycoplasma miroungigenitalium sp. nov. is proposed with the type strain ES2806-GENT (=NCTC 14429T=DSM 110944T) and representative strains ES3157-GEN-MYC and ES3225-GEN-MYC, Mycoplasma phocoenae sp. nov. is proposed with the type strain C264-GENT (=NCTC 14344T=DSM 110687T) and Mycoplasma phocoeninasale sp. nov. is proposed with the type strain C264-NAST (=NCTC 14343T=DSM 110688T) and representative strain CSL7498. The genome G+C contents are 24.06, 30.09, 28.49 and 29.05% and the complete genome sizes are 779 550, 815 486, 693 115, and 776 009 bp for strains ES2806-NAST, ES2806-GENT, C264-GENT and C264-NAST, respectively.
COVID-19 and its clinical severity are associated with alterations of plasma sphingolipids and enzyme activities of sphingomyelinase and ceramidase
Authors: Mühle Christiane , Kremer Andreas , Vetter Marcel , Schmid Jonas , Achenbach Susanne , Schumacher Fabian , Lenz Bernd , Cougoule Céline , Hoertel Nicolas , Carpinteiro Alexander , Gulbins Erich , Kleuser Burkhard , Kornhuber Johannes
Published: January 2022

In the current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19), a better understanding of the underlying mechanisms is essential to reduce morbidity and mortality and treat post-COVID-19 disease. Here, we analyzed alterations of sphingolipids and their metabolizing enzymes in 125 men and 74 women tested positive for SARS-CoV-2 and hospitalized with mild, moderate or severe symptoms or after convalescence.

The activities of acid and neutral sphingomyelinases (ASM, NSM), which hydrolyze sphingomyelin to ceramide, were significantly increased in COVID-19 patients, while the activity of neutral ceramidase (NC), which hydrolyzes ceramide to sphingosine, was reduced. These alterations could each contribute to elevated ceramide levels in patients. Accordingly, liquid chromatography tandem-mass spectrometry (LC-MS/MS) yielded increased levels of ceramides 16:0 and 18:0 with highest levels in severely affected patients and similar effects for dihydroceramides 16:0 and 18:0, whereas levels of (dihydro-)ceramides 24:0 were reduced. Furthermore, sphingomyelin 20:0; 22:0 and 24:0 as substrates of ASM and NSM as well as their dihydrosphingomyelin counterparts were reduced in patients as well as sphingosine-1-phosphate further downstream of NC activity. Effects of NSM, NC, ceramides and sphingomyelins remained significant after Bonferroni correction. SARS-CoV-2 antibody levels in convalescent patients were associated with age but none of the sphingolipid parameters. Based on our data, COVID-19 is associated with a dysregulation of sphingolipid homeostasis in a severity-dependent manner, particularly focused around a reduction of sphingomyelins and an accumulation of ceramides by increased enzyme activities leading to ceramide elevation (ASM, NSM) combined with a decreased activity of enzymes (NC) reducing ceramide levels. The potential of a combined sphingolipid/enzyme pattern as a diagnostic and prognostic marker and therapeutic target deserves further exploration.
Severe acute respiratory disease in American mink (Neovison vison) experimentally infected with SARS-CoV-2
Authors: Adney Danielle R. , Lovaglio Jamie , Schulz Jonathan E. , Yinda Claude Kwe , Avanzato Victoria A. , Haddock Elaine , Port Julia R. , Holbrook Myndi G. , Hanley Patrick W. , Saturday Greg , Scott Dana , Spengler Jessica R. , Tansey Cassandra , Cossaboom Caitlin M. , Wendling Natalie M. , Martens Craig , Easley John , Yap Seng Wai , Seifert Stephanie N. , Munster Vincent J.
Published: January 2022

An animal model that fully recapitulates severe COVID-19 presentation in humans has been a top priority since the discovery of SARS-CoV-2 in 2019. Although multiple animal models are available for mild to moderate clinical disease, a non-transgenic model that develops severe acute respiratory disease has not been described. Mink experimentally infected with SARS-CoV-2 developed severe acute respiratory disease, as evident by clinical respiratory disease, radiological, and histological changes. Virus was detected in nasal, oral, rectal, and fur swabs. Deep sequencing of SARS-CoV-2 from oral swabs and lung tissue samples showed repeated enrichment for a mutation in the gene encoding for nonstructural protein 6 in open reading frame 1a/1ab. Together, these data indicate that American mink develop clinical features characteristic of severe COVID19 and as such, are uniquely suited to test viral countermeasures.

One Sentence Summary

SARS-CoV-2 infected mink develop severe respiratory disease that recapitulates some components of severe acute respiratory disease, including ARDS.
A scalp geometry based parameter-space for optimization and implementation of conventional TMS coil placement
Authors: Jiang Yihan , Du Boqi , Chen Yuanyuan , Wei Lijiang , Cao ZhengCao , Zhang Zong , Xie Cong , Li Quanqun , Cai Zhongxuan , Li Zheng , Zhu Chaozhe
Published: January 2022

Transcranial magnetic stimulation efficacy is largely dependent upon coil position and orientation. A good method for describing coil placement is required for both computational optimization (planning) and actual placement (implementation). In coordinate dependent parameter-spaces (CDPs), three-dimensional coordinates are used to represent coil position and three orthogonal unit vectors are used to represent coil orientation. A CDP can precisely describe arbitrary coil placement; therefore it offers great advantage in computational optimization which checks through all possible placements. However, a neuronavigation system is usually required to accurately implement the optimized CDP parameters on a participant’s head. Routine clinical practice, on the other hand, often uses the International 10-20 system to describe coil placement. Although the 10-20 system can only perform modeling and placement at limited scalp landmarks, it allows the synthesis of different individuals’ targeting effects to find group-optimal parameters; it also allows manual placement, which is important for commonly-seen use cases without individual MRI scans and navigation devices. This study proposes a new scalp geometry based parameter-space (SGP), integrating the advantages of CDP and 10-20 methods. Our SGP 1) can quantitatively specify all possible conventional coil positions and orientations on an individual’s scalp, which is important for electrical modeling and optimization, 2) maintains inter-individual correspondence, which is important for synthesizing TMS effects from different individuals and studies. 3) enables fast and simple manual implementation. Demonstration experiments were conducted to illustrate the application of an SGP-based framework for both individual and group-based optimization. A measurement experiment was performed to evaluate speed, precision and reliability of SGP-based manual implementation; results show it surpasses previous manual placement methods.
4R-Tobacco-Cembranoid is a Positive Allosteric Modulator of the Alpha7 Nicotinic Acetylcholine Receptor that modulates inflammation-induced thermal hypersensitivity in mice
Authors: Rivera-García Luis G. , Francis-Malavé Adela M. , Wilson Torri D. , Ferchmin P. A. , Eterovic Vesna , Carrasquillo Yarimar
Published: January 2022

Alpha7 nicotinic acetylcholine receptors (α7nAChRs) are activated in response to inflammation and modulate pain in humans and rodent models. The use of α7nAChRs agonists as a therapeutic option for inflammation and pain is challenged by unwanted effects resulting from constant activation and/or desensitization of α7nAChRs. Positive allosteric modulators (PAMs) represent a compelling alternative as they increase endogenous nicotinic transmission but do not result in progressive desensitization or loss of receptor function. In the present study, we evaluated the function of the 4R tobacco cembranoid (4R) as a PAM of α7nAChR that reduces inflammation and pain-related behaviors in mouse models of inflammatory pain. Our electrophysiological experiments show that 4R potentiates choline-evoked currents in SH-SY5Y cells overexpressing α7nAChRs in a dose-dependent manner. At the behavioral level, we show that subcutaneous administration of 4R decreases inflammation-induced thermal but not tactile hypersensitivity or formalin-induced spontaneous nociceptive responses in both male and female mice. We further show reduced inflammation-induced paw edema in 4R-treated males, with no measurable effect observed in female mice. Altogether, the results from the experiments in this study identify 4R as a PAM of α7nAChRs that reduces thermal hypersensitivity in male and female mice and inflammation in a sex-specific manner. These findings highlight the use of 4R as a potential novel treatment strategy for pain and inflammation.
How does the host community structure affect the epidemiological dynamics of emerging infectious diseases?
Authors: Voinson Marina , Smadi Charline , Billiard Sylvain
Published: January 2022

Many pathogens, especially those responsible for emerging infectious diseases, are transmitted in a host community. How the host community structure affects an epidemic is still debated, particularly whether increasing the host community complexity would tend to amplify or dilute the incidence of an epidemic in a target population,e.g. humans or cattle. In this paper, we build a stochastic SIR model and compare epidemiological dynamics in a target population between three simple host community structures with an increasing complexity. Globally, our results show two possible main outcomes. First, an intermediate host can have a diluting effect by preventing the direct transmission from hosts to the target population, thus reducing the prevalence of infection. Second, when two sources of infection are considered, the effects of the epidemic are generally amplified. By highlighting that the structure of the ecological hosts network can dramatically affect epidemics, our results may have implications for the control of emerging infectious diseases.
Real-time precision opto-control of chemical processes in live cells
Authors: Clark Matthew G. , Gonzalez Gil , Aldana-Mendoza Jesus , Carlsen Mark S. , Eakins Gregory , Zhang Chi
Published: January 2022

Precision control of molecular activities and chemical reactions in live cells is a long-sought capability by life scientists. No existing technology can probe molecular targets in cells and simultaneously control the activities of only these targets at high spatial precision and on the fly. We develop a real-time precision opto-control (RPOC) technology that detects a chemical-specific optical response from molecular targets during laser scanning and uses the optical signal to trigger an acousto-optic modulator, which allows a separate laser beam to only interact with the molecules of interest without affecting other parts of the sample. RPOC can automatically probe and control biomolecular activities and chemical processes in dynamic living samples with submicron spatial accuracy, nanoseconds response time, and high chemical specificity.
Evaluation of Various Drugs’ Influence on Alzheimer’s Disease Progress Using a New Analytical Model Based on Cellular Automata
Authors: Jafari Niloofar , Golabi Faegheh , Ebrahimi-kalan Abbas , Sarbaz Yashar
Published: January 2022

This article aims to introduce and propose a novel mathematical model for the study of Alzheimer’s disease (AD) progress. The presented model is based on Cellular Automata for better representation of AD progression. The differential equations of the Puri-Li model are utilized to calculate the number of Amyloid-β molecules. Also, a new definition for AD rate is presented in this study. Moreover, other useful factors such as Critical Rate (CR) and Warning Rate (WR) are defined to determine the status of AD progression. To get exact insight into the neuron-to-neuron communications, the model is obtained for a 3×3 neuron system to investigate the influence of drug injection on the reduction of AR, CR, and WR factors. It is shown that using drugs can decrease AR and CR factors and also enhance the WR. The presented study can be utilized for the investigation of various factors in the control and treatment of AD progression.