bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant human Hsp110-gp100 chaperone complex vaccine is nontoxic and induces response in advanced stage melanoma patients
Authors: Wach Michael M. , Subjeck John R. , Wang Xiang-Yang , Repasky Elizabeth , Matsuzaki Junko , Yu Han , Wang Chong , Fisher Daniel , Skitzki Joseph J. , Kane John M.
Published: March 2022

Heat shock proteins (hsp) are intracellular chaperones that possess extracellular immunostimulatory properties when complexed with antigens. A recombinant Hsp110-gp100 chaperone complex vaccine showed an antitumor response and prolonged survival in murine melanoma. A phase Ib dose-escalation study of a recombinant human Hsp110-gp100 vaccine in advanced-stage melanoma patients was performed to evaluate toxicity, immunostimulatory potential and clinical response. Patients with pretreated, unresectable stage IIIB/C/IV melanoma received the chaperone complex vaccine in a dose-escalation protocol; three vaccinations over a 43-day-period. Tumor response, clinical toxicity and immune response were measured. Ten patients (eight female, median age 70 years) were enrolled and two patients had grade 1 adverse events; minor skin rash, hyperhidrosis and fever (no grade 2 or higher adverse events). Median progression-free survival was longer for lower vaccine doses as compared to the maximum dose of 180 mcg (4.5 vs. 2.9 months; P = 0.018). The lowest dose patients (30 and 60 mcg) had clinical tumor responses (one partial response, one stable disease). CD8+ T cell interferon-γ responses to gp100 were greater in the clinically responding patients. A pattern of B cell responses to vaccination was not observed. Regulatory T cell populations and co-stimulatory molecules including cytotoxic T-lymphocyte-associated protein 4 and PD-1 appeared to differ in responders versus nonresponders. A fully recombinant human Hsp110-gp100 chaperone complex vaccine had minimal toxicity, measurable tumor responses at lower doses and produced peripheral CD8+ T cell activation in patients with advanced, pretreated melanoma. Combination with currently available immunotherapies may augment clinical responses.
Bridging the Transition to Assisted Living
Authors: Huebner Carol Ann
Published: March 2022

The transition from independent living to assisted living is a significant life process that may be compared to crossing a bridge. Faith community nurses can support older adults through this transition. This article presents a conceptual meaning of transition, a framework with a spiritual dimension, and implications for Christian nurses. A case study illustrates how this transition typically occurs across time.
Promises and challenges: cabotegravir for preexposure prophylaxis
Authors: Spinelli Matthew A. , Grinsztejn Beatriz , Landovitz Raphael J.
Published: March 2022

Purpose of review

Tenofovir-based oral PrEP has been effective in reducing population-level HIV incidence in multiple settings, although disparities remain. Injectable cabotegravir-based PrEP is an alternative that may be attractive to individuals with adherence challenges or who do not desire to take a daily medication. We review promises and challenges of cabotegravir-based PrEP.

Recent findings

Cabotegravir has demonstrated higher effectiveness than oral PrEP in two randomized trials, with a hazard ratio of 0.31 for HIV incidence among MSM and transgender women across multiple settings [95% confidence interval (CI) 0.18–0.62] and 0.11 for cisgender women in sub-Saharan Africa (95% CI 0.040.32). Cabotegravir was also highly effective among populations with disproportionate HIV incidence. Although cabotegravir breakthrough was rare, diagnosis was delayed with use of antigen/antibody-based HIV tests, and resistance occurred with breakthrough infections. Implementation will need to overcome several challenges, including HIV RNA laboratory monitoring not being widely available, requirement for additional staff time and clinic space, and need to provide oral medication during interruptions in dosing.

Cabotegravir-based PrEP is a highly effective additional PrEP option that will expand HIV prevention options. For successful roll-out, strategies for streamlined and accessible delivery of cabotegravir in real-world settings will need to be developed.
THE TARGET SIGN
Authors: Newman Hadas , Perlman Ido , Pras Eran , Rozenberg Assaf , Ben-Yosef Tamar , Iovino Claudio , Simonelli Francesca , Di Iorio Valentina , Rotenstreich Ygal , Katzburg Etti , Ehrenberg Miriam , Iglicki Matias , Zur Dinah
Published: March 2022

Purpose:

Retinol dehydrogenase 5 (RDH5)–related fundus albipunctatus can present with phenotypic variability. Our purpose was to investigate new clinical characteristics and multimodal imaging findings in patients from different ethnic origins, carrying different mutations.

Methods:

Multicenter international retrospective case series of 18 patients with genetically confirmed RDH5-related fundus albipunctatus. Patients' files were reviewed for fundus images, visual acuity, macular optical coherence tomography scans, near-infrared images, fundus autofluorescence, electroretinogram, and genetic mutations. Imaging and electroretinogram findings.

Results:

All eyes (n = 36, 100%) showed small circular findings seen on near-infrared images, termed as the “target sign,” correlating to the yellowish dots seen clinically and to the distinct hyperreflective linear lesions on optical coherence tomography at the level between external limiting membrane and retinal pigment epithelium. Perifoveal atrophy with foveal sparing was seen in 4 eyes of 2 patients (both RDH5—c.160C>T, p.R54X mutation). Fundus autofluorescence revealed small hyperautofluorescent dots (n = 16, 44.4%). Scotopic electroretinograms were significantly reduced in all cases with an electronegative pattern, 66.7% displayed cone dysfunction.

Conclusion:

Our results show distinct imaging findings present in all patients with fundus albipunctatus independent of ethnicity or genetic mutation. Our results can facilitate the current algorithm to diagnose RDH5-related fundus albipunctatus and allow for targeted genetic testing.
NONSURGICAL RESOLUTION OF FULL-THICKNESS MACULAR HOLES WITHOUT VITREOMACULAR TRACTION
Authors: Richards Paige J. , Kulkarni Amol D. , Nork T. Michael , Leys Monique , Hinkle David , Conlin Karina A. , Chang Stanley , Chang Jonathan S.
Published: March 2022

Background/Purpose:

The purpose of this study was to report a case series of full-thickness macular holes without vitreomacular traction that resolved without surgery.

Methods:

This study is a retrospective case series of 11 patients who demonstrated closure of full-thickness macular holes without surgical intervention.

Results:

All full-thickness macular holes closed, with all patients having improvement in visual acuity. All but one of the cases had visual acuity better than 20/40 at last recorded visit. Most cases presented with associated epiretinal membrane (73%), cystoid changes (64%), defects <150 μm (80%), and resolved within 2 months (91%). Topical anti-inflammatory drops were used in 7 of 11 cases, and dorzolamide was used in one case.

Conclusion:

Full-thickness macular holes can develop in eyes without the presence of vitreomacular traction. Topical therapy without vitrectomy may be particularly helpful in closure of full-thickness macular holes with associated cystoid macular edema. Holes with a lamellar hole component may spontaneously resolve as part of a retinal remodeling process.
RAPID PENTOSAN POLYSULFATE SODIUM MACULOPATHY PROGRESSION
Authors: Somisetty Swathi , Santina Ahmad , Abraham Neda , Lu Anthony , Morales Veronica Romero , Sarraf David
Published: March 2022

Purpose:

The purpose of this study was to report a unique case of pentosan polysulfate sodium (PPS) maculopathy with remarkable rapid progression over 2 years. These findings show the importance of early detection of macular disease to limit toxic exposure and reduce the risk of progression.

Methods:

Multimodal retinal imaging including fundus autofluorescence, near-infrared reflectance with pseudocolor, and spectral domain optical coherence tomography was performed in an elderly patient with a history of PPS therapy (cumulative dose of 1,205 g) at baseline and 2 years later.

Results:

Baseline multimodal retinal imaging failed to show significant macular findings of PPS toxicity in either eye, but on repeat evaluation 2 years later, advanced features of PPS maculopathy were detected in both eyes with fundus autofluorescence, near-infrared reflectance, pseudocolor, and spectral domain optical coherence tomography.

Conclusion:

This report describes a remarkable case of rapid progression of PPS maculopathy as documented with multimodal retinal imaging. The dramatic progression of macular findings over just 2 years underscores the importance of early detection and prompt withdrawal of therapy, if systemically feasible, to retard the development and rate of progression of PPS maculopathy.
In-hospital venous thromboembolism: are glucocorticoids a prime suspect?
Authors: Feldpausch Brian , Giuliano Christopher , Hartner Carrie L. , Edwin Stephanie B.
Published: March 2022

The objective of the study was to determine whether glucocorticoid use is associated with an increased incidence of in-hospital VTE. We conducted a case–control study of patients with an in-hospital VTE from October 2015 to December 2019. Adult patient cases were identified by ICD-10 codes for acute venous thromboembolism. Controls were selected from all patients without a VTE diagnosis and matched by hospital length of stay and admission type (medical/surgical). Patients were excluded if they had a history of VTE, received therapeutic anticoagulation, or were pregnant. All patients were evaluated to determine the presence or absence of glucocorticoid exposure. Glucocorticoid dose, duration, and route of administration were assessed for patients with steroid exposure. Overall, 78 patients with VTE and 234 controls were included. Receipt of glucocorticoids within the preceding 90 days was similar between the VTE cases and controls (39.7 vs. 38.9%, P 
= 0.89). No differences were noted with regard to oral (21.8 vs. 19.2%, P = 0.62), intravenous (30.8 vs. 29.1%. P = 0.774), or inhaled (6.4 vs. 10.3%, P = 0.31) routes of administration between VTE case and control patients.

Cumulative prednisone equivalent doses were similar between cases and controls (877 ± 1366 vs. 697 ± 1963 mg, P = 0.435). The risk of in-hospital venous thromboembolism was not influenced by glucocorticoid exposure within the past 90 days. These results were consistent across all routes of administration, exposure time, and steroid dose. Blood Coagul Fibrinolysis 33:000–000 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Implantation of transjugular intrahepatic portosystemic shunt (TIPS): indication and patient selection
Authors: Bettinger Dominik , Thimme Robert , Schultheiß Michael
Published: March 2022

Purpose of review

This review summarizes indications and contraindications for implantation of transjugular intrahepatic portosystemic shunt (TIPS). Further, patient selection strategies are discussed.

Recent findings

TIPS implantation is a highly effective treatment for portal hypertension. Main indications are ascites and variceal bleeding in patients with liver cirrhosis. There is growing evidence that early TIPS implantation after variceal bleeding is associated with an improved survival (preemptive TIPS).

Preliminary data also suggest that an analogous concept of early TIPS implantation may be beneficial for patients with ascites. Further, well-selected patients with acute or chronic nonmalignant portal vein thrombosis can be effectively treated with TIPS implantation. In contrast, there is generally no recommendation for TIPS implantation in patients with hepatic veno-occlusive disease, noncirrhotic portal hypertension or prior before surgery to avoid complications of portal hypertension. Apart from evidence-based patient selection, the newly developed FIPS score can be an objective component in decision-making.

Consideration of well-established indications and contraindications for TIPS implantation as well as concise patient selection criteria are essential for an optimal outcome after TIPS implantation.
Clear Cell Neoplasms of Salivary Glands: A Diagnostic Challenge
Authors: Skalova Alena , Leivo Ilmo , Hellquist Henrik , Simpson Roderick H.W. , Vander Poorten Vincent , Willems Stefan M. , Mosaieby Elaheh , Slouka David , Ferlito Alfio
Published: March 2022

This review focuses on the heterogenous group of clear cell neoplasms of salivary glands and attempts to identify major differential diagnostic features. Within the head and neck region, clear cells are found most commonly in salivary gland tumors, but may also be seen in tumors of squamous or odontogenic epithelial origin, primary or metastatic carcinomas, benign or malignant melanocytic lesions, or benign or malignant mesenchymal tumors. Clear cells occur fairly commonly among a wide variety of salivary gland neoplasms, but mostly they constitute only a minor component of the tumor cell population. Clear cells represent a major diagnostic feature in two salivary gland neoplasms, epithelial-myoepithelial carcinoma and hyalinizing clear cell carcinoma. In addition, salivary gland neoplasms composed predominantly of clear cells could also include clear cell variants of other salivary neoplasms, such as mucoepidermoid carcinoma and myoepithelial carcinoma, but their tumor type-specific histologic features may only be available in limited nonclear cell areas of the tumor. Diagnosing predominantly clear cell salivary gland tumors is difficult because the immunoprofiles and morphologic features may overlap and the same tumor entity may also have a wide range of other histologic presentations. Many salivary gland tumors are characterized by tumor type-specific genomic alterations, particularly gene fusions of the ETV6 gene in secretory carcinoma, the MYB and MYBL1 genes in adenoid cystic carcinoma, the MAML2 gene in mucoepidermoid carcinoma, the EWSR1 gene in hyalinizing clear cell carcinoma, and others. Thus, along with conventional histopathologic examination and immunoprofiling, molecular and genetic tests may be important in the diagnosis of salivary gland clear cell tumors by demonstrating genetic alterations specific to them.
Health Resource Use in Survivors of Pediatric Septic Shock in the United States
Authors: Maddux Aline B. , Zimmerman Jerry J. , Banks Russell K. , Reeder Ron W. , Meert Kathleen L. , Czaja Angela S. , Berg Robert A. , Sapru Anil , Carcillo Joseph A. , Newth Christopher J. L. , Quasney Michael W. , Mourani Peter M. ,   for the Life After Lapse Sepsis Evaluation (LAPSE) Investigators
Published: March 2022

OBJECTIVES:

To evaluate postdischarge health resource use in pediatric survivors of septic shock and determine patient and hospitalization factors associated with health resource use.

DESIGN

Secondary analyses of a multicenter prospective observational cohort study.

SETTING:

Twelve academic PICUs.

PATIENTS:

Children greater than or equal to 1 month and less than 18 years old hospitalized for community-acquired septic shock who survived to 1 year.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

For 308/338 patients (91%) with baseline and greater than or equal to one postdischarge survey, we evaluated readmission, emergency department (ED) visits, new medication class, and new device class use during the year after sepsis. Using negative binomial regression with bidirectional stepwise selection, we identified factors associated with each outcome. Median age was 7 years (interquartile range, 2–13), 157 (51%) had a chronic condition, and nearly all patients had insurance (private [n = 135; 44%] or government [n = 157; 51%]). During the year after sepsis, 128 patients (42%) were readmitted, 145 (47%) had an ED visit, 156 (51%) started a new medication class, and 102 (33%) instituted a new device class. Having a complex chronic condition was independently associated with readmission and ED visit. Documented infection and higher sum of Pediatric Logistic Organ Dysfunction--2 hematologic score were associated with readmission, whereas younger age and having a noncomplex chronic condition were associated with ED visit. Factors associated with new medication class use were private insurance, neurologic insult, and longer PICU stays. Factors associated with new device class use were preadmission chemotherapy or radiotherapy, presepsis Functional Status Scale score, and ventilation duration greater than or equal to 10 days. Of patients who had a new medication or device class, most had a readmission (56% and 61%) or ED visit (62% and 67%).

CONCLUSIONS:

Children with septic shock represent a high-risk cohort with high-resource needs after discharge. Interventions and targeted outcomes to mitigate postdischarge resource use may differ based on patients’ preexisting conditions.
Caregiver Practices and Knowledge Regarding Leftover Prescription Medications in Homes With Children
Authors: Renny Madeline H. , Thaker Riddhi H. , Dayan Peter S.
Published: March 2022

Objectives

The aims of the study were to determine the frequency of and factors associated with leftover or expired prescription medication (“leftover medication”) presence in homes with children and to assess caregivers' reported behaviors and knowledge regarding disposal of leftover medications in the home.

Methods

This study is a planned secondary analysis from a survey of primary caregivers of children aged 1 to 17 years presenting to an emergency department. The survey assessed leftover medications in the home and medication disposal practices, knowledge, and guidance. The survey was developed iteratively and pilot tested. Multivariable logistic regression was used to identify factors associated with leftover medication presence in the home.

Results

We enrolled 550 primary caregivers; 97 of the 538 analyzed (18.0%; 95% confidence interval [CI], 14.8–21.5) reported having leftover medications in their home, most commonly antibiotics and opioids. Of respondents, 217/536 (40.5%) reported not knowing how to properly dispose of medications and only 88/535 (16.4%) reported receiving guidance regarding medication disposal. Most caregivers reported throwing leftover medications in the trash (55.7%) or flushing them down the toilet (38.5%). Caregivers with private insurance for their child were more likely to have leftover medications (adjusted odds ratio [aOR], 1.99; CI, 1.15–3.44), whereas Hispanic caregivers (aOR, 0.24; CI, 0.14–0.42) and those who received guidance on leftover medications (aOR, 0.30; CI, 0.11–0.81) were less likely to have leftover medications in the home.

Conclusions

Leftover medications are commonly stored in homes with children and most caregivers do not receive guidance on medication disposal. Improved education and targeted interventions are needed to ensure proper medication disposal practices.
Clinician Knowledge of Incontinence-Associated Dermatitis
Authors: Barakat-Johnson Michelle , Stephenson John , Basjarahil Shifa , Campbell Jayne , Cunich Michelle , Disher Gary , Geering Samara , Ko Natalie , Lai Michelle , Leahy Catherine , Leong Thomas , McClure Eve , O'Grady Melissa , Walsh Joan , White Kate , Coyer Fiona
Published: March 2022

PURPOSE:

This study examined clinicians' knowledge of incontinence-associated dermatitis (IAD) using the Barakat-Johnson Incontinence-Associated Dermatitis Knowledge Tool (Know-IAD).

Design:

A cross-sectional multicenter survey.

SUBJECTS AND SETTING:

The setting was 6 hospitals across 5 health districts in New South Wales, Australia. The participants were nurses (registered nurses and enrolled nurses), physicians, allied health (occupational therapists, dietitians, and physiotherapists), and students (nursing and allied health).

METHODS:

Data about IAD knowledge were collected from November 2019 to January 2020. The Know-IAD, an 18-item validated instrument that measures knowledge of IAD in 3 domains (etiology and risk, classification and diagnosis, and prevention and management), was administered to a cross section of eligible clinicians. The participants anonymously completed hard copy surveys. Descriptive and exploratory analyses were conducted to quantify clinicians' knowledge about the etiology and risk, classification and diagnosis, and prevention and management of IAD. A mean knowledge score of 70% was considered to be satisfactory.

RESULTS:

Four hundred twelve respondents completed the survey. One hundred twenty nine respondents (31.3%) achieved 70% correct responses and greater for the entire set of items. For the etiology and risk domain, 348 respondents (84.5%) obtained a score of 70% correct responses and greater, 67 respondents (16.3%) achieved 70% correct responses and greater for the classification and diagnosis domain, and 84 respondents (20.4%) achieved 70% correct responses and greater for the prevention and management domain.

CONCLUSION:

Clinicians tend to have low knowledge and recognition of IAD, particularly in the areas of classification and diagnosis along with prevention and management. They tend to have higher knowledge of how IAD is caused and the risk factors. This study has identified knowledge gaps for further education that can improve assessment, prevention, and management of IAD.
Factors Influencing Nursing Students' Knowledge of and Attitudes Toward Urinary Incontinence
Authors: Cheng Winnie Lai-Sheung , Kam Mei Kuk , Liong Yu Yan , Tang Tat Cheong , Tse Eleni Hiu Lam , Tse Ho Kwan , Tsao Wing Hei , Cheung Ka Chai
Published: March 2022

PURPOSE:

This study aimed to determine nursing students' knowledge about and attitudes toward patients with urinary incontinence.

SUBJECTS AND SETTING:

The sample comprised 392 nursing students from 5 educational institutions in Hong Kong; all participants were enrolled in year 4 or 5 of their undergraduate nursing program, and all had completed formal education on urinary incontinence and clinical experience caring for patients with urinary incontinence.

METHODS:

A cross-sectional survey was conducted in February 2017. Participants completed a 55-item questionnaire that included items querying demographic and pertinent professional background information, along with 2 validated instruments: the Urinary Incontinence Knowledge Scale (UIKS) and the Urinary Incontinence Attitude Scale (UIAS). Analysis of variance was performed to compare the differences in scores among nursing students based on demographic or educational background. Pearson's correlation coefficient or χ2 was used to examine the relationships between variables and multivariate regression analyses were performed to identify the predictors of attitude toward urinary incontinence.

RESULTS:

Urinary incontinence knowledge was moderate (mean 22.0/30, SD 4.4) and attitudes about urinary incontinence were positive (mean 41.6/60, SD 4.5). There was a significant correlation between attitudes and knowledge (r = 0.175, P = .001), institution at which the students received training (χ2 = 161.790, P = .000), and the experience of having taken a course that included instruction about urinary incontinence (χ2 = 37.707, P = .014). Regression analysis revealed that knowledge and institution were predictors of attitudes. Participants reported high level of interest in learning more about urinary incontinence (71.2%).

CONCLUSIONS:

Nursing students residing in Hong Kong have a moderate level of knowledge and positive attitude toward urinary incontinence. This study suggests that educational institution and specific instruction about urinary incontinence play key roles in developing positive attitudes toward caring for patients with urinary incontinence.
Shared Decision-Making and Short-Course Radiotherapy for Operable Rectal Adenocarcinoma
Authors: Col Nananda F. , Haugen Vicki
Published: March 2022

BACKGROUND:

As new treatment options for colorectal cancer (CRC) emerge, physicians and WOC nurses must be prepared to assist patients to choose care that meets their needs and preferences. A patient with T2N0M0 rectal adenocarcinoma was offered the US current standard of practice; he was not offered alternative treatment options. This case study emphasizes the need to ensure patients are offered all reasonable options for treatment. Shared decision-making is a process that helps patients actively participate in their heath choices rather than exclusively relying on the judgment of a health care provider.

CASE:

Mr J was a 70-year-old man with operable CRC who sought care at a health care facility in his community. He was offered a single option, based on standard of care for this tumor stage: long-course neoadjuvant chemoradiotherapy followed by surgery and additional chemotherapy. After seeking a second opinion at a cancer care center in another state, Mr J chose to undergo a viable alternative treatment option (short-course radiotherapy, followed by surgery, with chemotherapy contingent on his nodal status post-surgery). No nodal involvement was found post- surgery (T2N0M0) enabling him to avoid postoperative chemotherapy.

CONCLUSIONS:

This case illustrates the need for all health care providers and carers to regularly engage in shared decision-making when choosing among treatment options. In this case, short-course radiotherapy offered Mr J a shorter duration of treatment and avoided the risk for adverse side effects associated with chemotherapy, resulting in improved health-related quality of life. Initial omission to disclose all treatment options to Mr J may have reflected the preferences of the surgeon, institutional financial pressures, or discomfort with shared decision-making, but it failed to provide him with full range of options, given his diagnosis and tumor stage. All members of the patient's care team, including the WOC nurse, play a pivotal role in ensuring transparency in medical care, including advocating for shared decision-making where patients are made aware of all viable treatments, followed by supporting the patient as they reach a decision.
Incidence of Medical Adhesive–Related Skin Injuries and Associated Factors After Pediatric Congenital Heart Surgery
Authors: Crespo Jeiel Carlos Lamônica , Reuter do Amaral Daniela , Campanili Ticiane Carolina Gonçalves Faustino , Cunha Ligia Cristina Camara , Ferreira Fatima Gil , Gallas Filomena Regina Gomes , Palomo Jurema da Silva Herbas , Ferretti-Rebustini Renata Eloah de Lucena
Published: March 2022

PURPOSE:

The aim of this study was to identify the incidence, characteristics, and factors associated with medical adhesive–related skin injuries (MARSI).

DESIGN:

Prospective cohort study.

SUBJECTS AND SETTINGS:

The sample comprised 136 children in the postoperative period after congenital heart surgery. The study setting was in a 31-bed pediatric surgical intensive care unit (ICU) of a university hospital in Sao Paulo, Brazil.

METHODS:

Patients were followed from admission, with daily skin assessments, until the onset of MARSI or ICU discharge. Outcomes were compared by Fisher's exact test, Pearson's χ2 test, Mann-Whitney test, Brunner-Munzel test, and Welch 2-sample t test.

RESULTS:

The incidence of MARSI was 60.3%, with 85 injuries in 82 patients. The highest occurrence was on postoperative day 2 (27 wounds; 31.8%). The most frequent medical adhesive associated with MARSI was transparent film dressing (n = 74; 86.6%). Factors associated with MARSI were age (P = .000), number of devices inserted (P = .000), Braden Q Scale score (P = .005), duration of surgery (P = .021), cardiopulmonary bypass duration (P = .000), duration of mechanical ventilation (P = .000), and length of ICU stay (P = .000). Children who developed MARSI received more blood components (P = .039), vasopressors (P = .000), and corticosteroids (P = 0.000); required longer sedation (P = .000); and had more edema (P = .001).

CONCLUSION:

This high incidence indicates the need for greater awareness and prompt action in response to MARSI. Polyurethane transparent film without concurrent use of a skin barrier product should be avoided.
Influence of Foot Ulceration on All-Cause and Cardiovascular Mortality in Diabetic Patients
Authors: Qiu Liangzhi , Li Yongjie , Yang Chuan , Mao Xiaoqun , Mai Lifang , Zhu Lisi , Xie Wen
Published: March 2022

PURPOSE:

The purpose of this study was to analyze the influence of a diabetic foot ulcer on all-cause and cardiovascular disease (CVD) mortality.

DESIGN:

Retrospective case-control study.

SUBJECTS AND SETTING OUTPATIENTS:

Eighty-eight patients with new-onset diabetic foot ulceration (DFU) were paired with 176 patients without DFU (controls). The study setting was the Department of Endocrinology, Sun Yat-sen Memorial Hospital, located in Guangzhou, China.

METHODS:

Cause-specific mortality was recorded during a median follow-up duration of 6.20 years up to 1 March 2016. Records review dates were from January 1, 2004, to December 31, 2010.

RESULTS:

The all-cause mortality rate for the DFU group and the control group was 48.9% and 22.7%, respectively. The risk of all-cause death in the DFU group was 3.126 times higher than that in the control group (risk ratio [RR]= 3.126; 95% CI, 1.998-4.891; P = .000). The CVD mortality rate of the DFU group and the control group was 12.5% and 6.8%, respectively. The risk of CVD death in the DFU group was 3.277 times higher than that in the control group (RR = 3.277; 95% CI, 1.392-7.715; P = .007).

CONCLUSIONS:

Development of a diabetic foot ulcer was associated with a significantly higher all-cause and CVD-related death risk than that in a control group of persons with diabetes mellitus without DFU.
Projected Augmented Reality (P-AR) for Enhancing Nursing Education About Pressure Injury
Authors: Bliss Donna Z. , Becker Adam J. , Gurvich Olga V. , Bradley Cynthia S. , Olson Erica Timko , Steffes Mary T. , Flaten Carol , Jameson Scott , Condon John P.
Published: March 2022

PURPOSE:

To describe results of a study evaluating a Projected Augmented Reality (P-AR) system for its potential to enhance nursing education about pressure injuries.

DESIGN:

Pilot evaluation survey.

SUBJECTS AND SETTING:

The sample comprised nursing students and faculty at a school of nursing in a large, Midwestern public university. A total of 32 participants, which included 27 students (30% BSN, 44% MN, and 26% DNP students; 81% female) and 5 faculty members (80% female) participated.

METHODS:

The P-AR system was prototyped using commercial-off-the-shelf components and software algorithms, applied to pressure injury nursing education content. After interaction with the P-AR system, participants completed a survey evaluating the following features of the P-AR system for potential: engagement, effectiveness, usefulness, user-friendliness, and realism, and users' overall impression and satisfaction with system features. Evaluation statements used a 5-level Likert-scale; open-ended questions about what was liked, disliked, or anything else offered opportunity for comments.

RESULTS:

Student and faculty median evaluation scores were 5 (strongly agree or very satisfied) and 4 (agree or satisfied) for nearly all evaluation and satisfaction statements. Students' satisfaction with “realism” received a median score of 3 (neutral). The P-AR system was refined to include realistic still and animated images.

CONCLUSION:

The P-AR system, an innovative technology using 3-dimensional dynamic images, was applied to nursing education content about pressure injury and was evaluated as having potential to enhance pressure injury teaching and learning. Education about complex processes of pressure injury development and management may benefit from using cutting-edge simulation technologies such as P-AR.
Abdominal Negative Pressure Wound Therapy Devices for Management of the Open Abdomen
Authors: Crumley Carolyn
Published: March 2022

PURPOSE:

The purpose of this technologic analysis was to analyze technologic features of abdominal negative pressure wound therapy (NPWT).

APPROACH:

Published literature regarding abdominal negative pressure wound therapy (aNPWT) devices was reviewed. A summary of management approaches for the open abdomen provides a foundation for understanding the benefits of aNPWT. Safety information regarding aNPWT was derived from the Manufacturer and User Facility Device Experience (MAUDE) Database.

CONCLUSIONS:

The open abdomen approach with temporary abdominal closure may be employed for patients with a variety of conditions. Specialized abdominal NPWT devices, either singly or in combination with other approaches, may contribute to improved outcomes in this high-risk patient population. Manufacturer recommendations and clinical guidelines should be followed to minimize patient risk.
Speleological and environmental history of Lida Ajer cave, western Sumatra
Authors: Louys Julien , Duval Mathieu , Price Gilbert J. , Westaway Kira , Zaim Yahdi , Rizal Yan ,   Aswan, Puspaningrum Mika , Trihascaryo Agus , Breitenbach Sebastian F. M. , Kwiecien Ola , Cai Yanjun , Higgins Penny , Albers Paul C. H. , de Vos John , Roberts Patrick
Published: March 2022

Some of the earliest evidence for the presence of modern humans in rainforests has come from the fossil deposits of Lida Ajer in Sumatra. Two human teeth from this cave were estimated to be 73–63 thousand years old, which is significantly older than some estimates of modern human migration out of Africa based on genetic data. The deposits were interpreted as being associated with a rainforest environment based largely on the presence of abundant orangutan fossils. As well as the main fossil-bearing chamber, fossil-bearing passages are present below a sinkhole, although the relationship between the different fossil deposits has only been tenuously established. Here, we provide significant new sedimentological, geochronological and palaeoecological data aimed at reconstructing the speleological and environmental history of the cave and the clastic and fossil deposits therein. Our data suggest that the Lida Ajer fossils were deposited during Marine Isotope Stage 4, with fossils from the lower passages older than the main fossil chamber. Our use of stable carbon and oxygen isotope analyses of mammalian tooth enamel demonstrates that early humans probably occupied a closed-canopy forest very similar to those present in the region today, although the fossil orangutans may have occupied a slightly different niche.

This article is part of the theme issue ‘Tropical forests in the deep human past’.
Tropical forests in the deep human past
Authors: Scerri Eleanor M. L. , Roberts Patrick , Yoshi Maezumi S. , Malhi Yadvinder
Published: March 2022

Since Darwin, studies of human evolution have tended to give primacy to open ‘savannah’ environments as the ecological cradle of our lineage, with dense tropical forests cast as hostile, unfavourable frontiers. These perceptions continue to shape both the geographical context of fieldwork as well as dominant narratives concerning hominin evolution. This paradigm persists despite new, ground-breaking research highlighting the role of tropical forests in the human story. For example, novel research in Africa's rainforests has uncovered archaeological sites dating back into the Pleistocene; genetic studies have revealed very deep human roots in Central and West Africa and in the tropics of Asia and the Pacific; an unprecedented number of coexistent hominin species have now been documented, including
Homo erectus
, the ‘Hobbit’ (
Homo floresiensis
),
Homo luzonensis
, Denisovans, and
Homo sapiens
. Some of the earliest members of our own species to reach South Asia, Southeast Asia, Oceania and the tropical Americas have shown an unexpected rapidity in their adaptation to even some of the more ‘extreme’ tropical settings. This includes the early human manipulation of species and even habitats. This volume builds on these currently disparate threads and, for the first time, draws together a group of interdisciplinary, agenda-setting papers that firmly places a broader spectrum of tropical environments at the heart of the deep human past.

This article is part of the theme issue ‘Tropical forests in the deep human past’.
Fatal affairs – conjugational transfer of a dinoflagellate-killing plasmid between marine Rhodobacterales
Authors: Tomasch Jürgen , Ringel Victoria , Wang Hui , Freese Heike M. , Bartling Pascal , Brinkmann Henner , Vollmers John , Jarek Michael , Wagner-Döbler Irene , Petersen Jörn
Published: March 2022

The roseobacter group of marine bacteria is characterized by a mosaic distribution of ecologically important phenotypes. These are often encoded on mobile extrachromosomal replicons. So far, conjugation had only been experimentally proven between the two model organisms

Phaeobacter inhibens

and

Dinoroseobacter shibae

. Here, we show that two large natural RepABC-type plasmids from

D. shibae

can be transferred into representatives of all known major

Rhodobacterales

lineages. Complete genome sequencing of the newly established

Phaeobacter inhibens

transconjugants confirmed their genomic integrity. The conjugated plasmids were stably maintained as single copy number replicons in the genuine as well as the new host. Co-cultivation of

Phaeobacter inhibens

and the transconjugants with the dinoflagellate Prorocentrum minimum demonstrated that

Phaeobacter inhibens

is a probiotic strain that improves the yield and stability of the dinoflagellate culture. The transconjugant carrying the 191 kb plasmid, but not the 126 kb sister plasmid, killed the dinoflagellate in co-culture.
Remodelling of potassium currents underlies arrhythmic action potential prolongation under beta-adrenergic stimulation in hypertrophic cardiomyopathy
Authors: Doste Ruben , Coppini Raffaele , Bueno-Orovio Alfonso
Published: March 2022

Hypertrophic cardiomyopathy (HCM) patients often present an enhanced arrhythmogenicity that can lead to lethal arrhythmias, especially during exercise. Recent studies have indicated an abnormal response of HCM cardiomyocytes to β-adrenergic receptor stimulation (β-ARS), with prolongation of their action potential rather than shortening. The mechanisms underlying this aberrant response to sympathetic stimulation and its possible proarrhythmic role remain unknown. The aims of this study are to investigate the key ionic mechanisms underlying the HCM abnormal response to β-ARS and the resultant repolarisation abnormalities using human-based experimental and computational methodologies. We integrated and calibrated the latest models of human ventricular electrophysiology and β-ARS using experimental measurements of human adult cardiomyocytes from control and HCM patients. Our major findings include: (1) the developed in silico models of β-ARS capture the behaviour observed in the experimental data, including the aberrant response of HCM cardiomyocytes to β-ARS; (2) the reduced increase of potassium currents under β-ARS was identified as the main mechanism of action potential prolongation in HCM, rather than a more sustained inward calcium current; (3) dispersion of repolarisation between healthy and HCM tissue was increased upon β-ARS, while transmural dispersion in HCM tissue was reduced; (4) models presenting repolarisation abnormalities were characterised by downregulation of the rapid delayed rectifier potassium current and the sodium-potassium pump, while inward currents were upregulated. In conclusion, our results identify causal relationships between the HCM phenotype and its arrhythmogenic response to β-ARS through the downregulation of potassium currents.
Loss of LGR5 through plasticity or gene ablation is associated with therapy resistance and enhanced MET-STAT3 signaling in colorectal cancer cells
Authors: Posey Tressie A. , Jacob Joan , Parkhurst Ashlyn N. , Subramanian Shraddha , Francisco Liezl E. , Liang Zhengdong , Carmon Kendra S.
Published: March 2022

Plasticity plays a significant role in colorectal tumor initiation, progression, and drug resistance. LGR5 is highly expressed in colorectal cancer (CRC) and marks functional cancer stem cells (CSCs). While LGR5+ CSCs are tumor-initiating, the majority of CRC cells that disseminate to seed metastases are LGR5-; however, reemergence of LGR5+ CSCs is required to drive metastatic outgrowth. LGR5+ CSCs have been shown to convert to LGR5- CRC cells in response to chemotherapies and this loss of LGR5 promotes a more drug-resistant phenotype. However, the molecular mechanisms that mediate plasticity remain elusive. In this study, we demonstrate conversion of LGR5+ CRC cells to an LGR5- state in response to chemotherapy, LGR5-targeted antibody-drug conjugates (ADCs), or LGR5 gene ablation, led to activation of STAT3. Further investigation revealed increased STAT3 activation occurred a result of increased MET activity. LGR5 overexpression decreased MET-STAT3 activity and sensitized CRC cells to therapy. STAT3 inhibition suppressed MET phosphorylation, while constitutively active STAT3 reduced LGR5 levels and increased MET activity, suggesting a potential feedback mechanism. Combination treatment of MET-STAT3 inhibitors with irinotecan or ADCs substantiated synergistic effects in vitro. In CRC xenografts, STAT3 inhibition combined with irinotecan enhanced tumor growth suppression and prolonged survival. These findings suggest a mechanism by which drug-resistant LGR5- CRC cells acquire a survival advantage through activation of MET-STAT3 and provide rationale for new treatment strategies that target CRC cell plasticity.

Significance

This study reveals that transition of highly plastic LGR5+ CRC cells to a more drug-resistant LGR5- state involves activation of MET-STAT3 signaling and provides new insight into therapeutic strategies to combat plasticity.
Developmentally programmed epigenome regulates cellular plasticity at the parental-to-zygote transition
Authors: Gleason Ryan J. , Semancik Christopher S. , Lakshminarayanan Gitanjali , Chen Xin
Published: March 2022

During metazoan development, the dramatic potency change from germline to embryos raises an important question regarding how the new life cycle is reset. Here, we report a tightly regulated epigenome landscape change from the parental germline to embryos in C. elegans. The epigenome is enriched with histone H3 in early-stage germ cells but switches to a histone variant H3.3-enriched epigenome in the mature egg. This H3.3-dominant epigenome persists in early-stage embryos until gastrulation, when the epigenome becomes H3 abundant again. We further demonstrate that this developmentally programmed H3 → H3.3 → H3 epigenome landscape change is regulated through differential expression of distinct histone gene clusters and is required for both germline integrity and early embryonic cellular plasticity. Together, this study reveals that a bimodal expression of H3 versus H3.3 is important for epigenetic reprogramming during gametogenesis and embryonic plasticity.

One Sentence Summary

Developmentally programmed epigenome resets cellular plasticity at the parental-to-zygote transition in C. elegans.
A New Power Law Linking the Speed to the Geometry of Tool-Tip Orientation in Teleoperation of a Robot-Assisted Surgical System
Authors: Zruya Or , Sharon Yarden , Kossowsky Hanna , Forni Fulvio , Geftler Alex , Nisky Ilana
Published: March 2022

Fine manipulation is important in dexterous tasks executed via teleoperation, including in robot-assisted surgery. Discovering fundamental laws of human movement can benefit the design and control of teleoperated systems, and the training of their users. These laws are formulated as motor invariants, such as the well-studied speed-curvature power law. However, while the majority of these laws characterize translational movements, fine manipulation requires controlling the orientation of objects as well. This subject has received little attention in human motor control studies. Here, we report a new power law linking the speed to the geometry in orientation control – humans rotate their hands with an angular speed that is exponentially related to the local change in the direction of rotation. We demonstrate this law in teleoperated tasks performed by surgeons using surgical robotics research platforms. Additionally, we show that the law’s parameters change slowly with the surgeons’ training, and are robust within participants across task segments and repetitions. The fact that this power law is a robust motor invariant suggests that it may be an outcome of sensorimotor control. It also opens questions about the nature of this control and how it can be harnessed for better control of human-teleoperated robotic systems.
Fusion with heat-resistant obscure (Hero) proteins have the potential to improve the molecular property of recombinant proteins
Authors: Morimoto Eri , Tsuboyama Kotaro , Tomari Yukihide
Published: March 2022

Although recombinant proteins are widely used in biotechnology and pharmaceutical industries, improving their solubility and stability is often a challenging issue. We recently discovered a class of highly unstructured heat-resistant obscure (Hero) proteins, which function to protect other “client” proteins in trans from various stresses in vitro and in vivo. Here, we show that fusion of Hero proteins in cis can enhance the molecular property of recombinant proteins. Fusion with Hero11 improved the otherwise challenging production of TAR DNA-binding protein of 43 kDa (TDP-43) in Escherichia coli. Moreover, fusing with Hero9 strongly protected the activity of firefly luciferase bearing destabilizing mutations against heat and other stress conditions. These data suggest that Hero proteins have the potential to be used as versatile stabilization tags for recombinant protein production.
Emotion schema effects on associative memory differ across emotion categories at the behavioural, physiological and neural level
Authors: Riegel Monika , Wypych Marek , Wierzba Małgorzata , Szczepanik Michał , Jednoróg Katarzyna , Vuilleumier Patrik , Marchewka Artur
Published: March 2022

Previous behavioural and neuroimaging studies have consistently reported that our memory is enhanced for associations congruent or incongruent with the structure of our prior knowledge, termed as schemas. However, it remains unclear if similar effects exist if encoded associations are emotional. Do emotional schemas also facilitate learning and subsequent retrieval? Does it depend on the type of experienced emotions?

Using a novel face-word pair association paradigm combined with fMRI and eye-tracking techniques, we demonstrated and replicated in two independent studies that congruency with emotion schemas and emotion category interact to affect associative memory. Overall, emotion schemas facilitated memory for associative context, paralleled by the recruitment of left inferior frontal gyrus (IFG) during successful encoding of emotionally congruent vs. incongruent pairs. However, emotion schema effects differed across two negative emotion categories: disgust and fear, with disgust remembered better than fear. The IFG engagement was higher during successful encoding of congruent vs. incongruent pairs, but only in the case of disgust, suggestive of more semantic processing involved in learning disgust-related associations. On the contrary, the encoding of congruent vs. incongruent fear-related pairs was supported by activity in right fusiform gyrus (FG), suggesting greater sensory processing of faces. Successful memory formation for congruent disgust-related pairs was associated with a higher loading of pupil dilation component related to sympathetic activation, longer gaze time on words compared to faces, and more gaze switches between the two. This was reversed for fear-related pairs where the faces attracted more attention, as reflected by longer gaze time (compared to words).

Overall, our results at the behavioural, physiological, and neural level converge to suggest that emotional congruency influences memory similar to semantic schemas. However, encoding processes and neural effects vary depending on emotion category, reflecting the differential role of semantic processing and visual attention processes in the modulation of memory by disgust and fear.