bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical Review of the Current Management of Frostbite Injuries
Authors: Zaramo Taborah Z. , Green Japjit K. , Janis Jeffrey E.
Published: February 2023

Frostbite is an injury that occurs when the skin and tissues are exposed to temperatures below their freezing point. This type of injury can lead to various complications such as functional loss, chronic pain, and psychological trauma. As such, understanding frostbite management is crucial for optimal patient care. A scoping review was conducted in February 2022 using PubMed, EMBASE, referenced articles and snowballing to identify relevant published articled using the terms “frostbite” and “management” and “surgery. Articles related to pathophysiology, classifications, radiography, complications, and medical and surgical management were included to formulate recommendations for practical management. Two hundred fifty-one articles were identified and 54 met inclusion criteria. Rapid rewarming in warm water (40-42 °C) remains the standard of care. Thrombolytic therapy has been shown in numerous studies to improve tissue salvage. Radiographic imaging has become crucial in the evaluation and management in frostbite injury. Current literature recommends delayed surgery with soft tissue debridement and bone scan-guided amputations. Surgical intervention including debridement, selective blister drainage, fasciotomies, surgical salvage, skin grafts‚ and flaps are often necessary in these patients towards optimizing form and function. The true prevalence and incidence of frostbite injury is unknown. A centralized national database will improve our understanding of the diagnostic and management modalities used in frostbite care. Plastic surgeons have a critical role in the management of frostbite care and must work with an interdisciplinary team to identify the best treatment route for optimal patient care.
Perception of Shame in the Plastic Surgery Field
Authors: AlQhtani Abdullh Z. , Alfaqeeh Faisal A. , Alabdulkarim Abdulaziz , AlSahabi Abdulrahman M.
Published: February 2023

Background:

Doctors and postgraduate students, especially those in the surgical field, face a highly stressful environment and are exposed to various emotions that have been studied, but the concept of shame-based learning (SBL) is still undergoing investigation, especially in the field of plastic surgery. SBL is a teaching method in which an instructor instills a sense of shame in the student, which may cause depression, anxiety, aggression, and poor job performance, leading to burnout, mental health illness, substance abuse, and suicide.

Methods:

From March to May 2022, two cross-sectional electronic surveys were conducted for residents and consultants in Saudi Arabia, respectively, which used a validated questionnaire to assess SBL.

Results:

Among the 70 responses received (29 residents and 41 consultants), 75.9% of the residents and 80.5% of the consultants were shamed. For residents, a wrong answer was the most common trigger for shame (44.8%), and the operating room was the most common place for it (51.7%). Losing self-confidence was the most common result of shaming (37.9%) and (41.4%) dealt with it by keeping it to themselves. Although 27.6% of residents stated that they had no negative effect, 20.7% stated that they were motivated. There are consultants who practice shaming directly or indirectly (65.9%), while some agreed that it is not necessary (80.5%).

Conclusions:

Although both groups agreed that SBL is unnecessary for the field and will not be practiced in the future, most residents and consultants experienced shame. The negative impact of SBL has several effects on the trainer, the teaching environment, and patient care.
Targeting YAP-mediated HSC death susceptibility and senescence for treatment of liver fibrosis
Authors: Du Kuo , Maeso-Díaz Raquel , Oh Seh Hoon , Wang Ergang , Chen Tianyi , Pan Christopher , Xiang Kun , Dutta Rajesh Kumar , Wang Xiao-Fan , Chi Jen-Tsan , Diehl Anna Mae
Published: February 2023

Background and Aims:

Liver fibrosis results from the accumulation of myofibroblasts (MFs) derived from quiescent HSCs, and yes-associated protein (YAP) controls this state transition. Although fibrosis is also influenced by HSC death and senescence, whether YAP regulates these processes and whether this could be leveraged to treat liver fibrosis are unknown.

Approach and Results:

YAP activity was manipulated in MF-HSCs to determine how YAP impacts susceptibility to pro-apoptotic senolytic agents or ferroptosis. Effects of senescence on YAP activity and susceptibility to apoptosis versus ferroptosis were also examined. CCl4-treated mice were treated with a ferroptosis inducer or pro-apoptotic senolytic to determine the effects on liver fibrosis. YAP was conditionally disrupted in MFs to determine how YAP activity in MF-HSC affects liver fibrosis in mouse models. Silencing YAP in cultured MF-HSCs induced HSC senescence and vulnerability to senolytics, and promoted ferroptosis resistance. Conversely, inducing HSC senescence suppressed YAP activity, increased sensitivity to senolytics, and decreased sensitivity to ferroptosis. Single-cell analysis of HSCs from fibrotic livers revealed heterogeneous sensitivity to ferroptosis, apoptosis, and senescence. In mice with chronic liver injury, neither the ferroptosis inducer nor senolytic improved fibrosis. However, selectively depleting YAP in MF-HSCs induced senescence and decreased liver injury and fibrosis.

Conclusion:

YAP determines whether MF-HSCs remain activated or become senescent. By regulating this state transition, Yap controls both HSC fibrogenic activity and susceptibility to distinct mechanisms for cell death. MF-HSC-specific YAP depletion induces senescence and protects injured livers from fibrosis. Clarifying determinants of HSC YAP activity may facilitate the development of novel anti-fibrotic therapies.
Survival by First-line Treatment Type and Timing of Progression Among Follicular Lymphoma Patients: A National Population-based Study in Sweden
Authors: Weibull Caroline E. , Wästerlid Tove , Wahlin Björn Engelbrekt , Andersson Per-Ola , Ekberg Sara , Lockmer Sandra , Enblad Gunilla , Crowther Michael J. , Kimby Eva , Smedby Karin E.
Published: February 2023

In follicular lymphoma (FL), progression of disease ≤24 months (POD24) has emerged as an important prognostic marker for overall survival (OS). We aimed to investigate survival more broadly by timing of progression and treatment in a national population-based setting. We identified 948 stage II-IV indolent FL patients in the Swedish Lymphoma Register diagnosed 2007–2014 who received first-line systemic therapy, followed through 2020. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by first POD at any time during follow-up using Cox regression. OS was predicted by POD using an illness-death model. During a median follow-up of 6.1 years (IQR: 3.5–8.4), 414 patients experienced POD (44%), of which 270 (65%) occurred ≤24 months. POD was represented by a transformation in 15% of cases. Compared to progression-free patients, POD increased all-cause mortality across treatments, but less so among patients treated with rituximab(R)-single (HR = 4.54, 95% CI: 2.76-7.47) than R-chemotherapy (HR = 8.17, 95% CI: 6.09-10.94). The effect of POD was similar following R-CHOP (HR = 8.97, 95% CI: 6.14-13.10) and BR (HR = 10.29, 95% CI: 5.60-18.91). The negative impact of POD on survival remained for progressions up to 5 years after R-chemotherapy, but was restricted to 2 years after R-single. After R-chemotherapy, the 5-year OS conditional on POD occurring at 12, 24, and 60 months was 34%, 46%, and 57% respectively, versus 78%, 82%, and 83% if progression-free. To conclude, POD before but also beyond 24 months is associated with worse survival, illustrating the need for individualized management for optimal care of FL patients.
Mucosal Atrophy Predicts Poorer Outcomes in Pediatric Ulcerative Colitis—A National Inception Cohort Study
Authors: Stenke Emily , Stallard Lorraine , Cooper Sarah , Dominik Anna , Pilkington Abigail , Sugrue Sheila , O’Sullivan Maureen , McDermott Michael , Quinn Shoana , Broderick Annemarie , Bourke Billy , Hussey Séamus
Published: February 2023

Background:

Outcomes in pediatric ulcerative colitis (UC) are heterogeneous and predictors of disease course eagerly sought. Mucosal atrophy (MA) is characterized by histological abnormalities of colonic intestinal glands.

Objective:

To determine the prevalence of MA in a national inception cohort of pediatric UC and its impact on outcomes.

Methods:

Irish children < 16 years old with UC are diagnosed at a single referral center. At diagnosis, patients underwent phenotyping by Paris classification and activity assessment by Pediatric Ulcerative Colitis Activity Index. Biopsies from all colonic segments were evaluated for MA. Patients were followed prospectively. The primary outcome was corticosteroid-free remission at 1 year. Secondary outcomes included relapse, treatment escalation, and colectomy by 2 years.

Results:

Of 251 pediatric patients with UC (mean age 11.8 years, 55% male), 38 (15%) had MA on diagnostic biopsy. Baseline characteristics were similar between groups with/without MA and there was no difference in steroid-free remission or rates of moderate-severe UC at 1 year. Patients with MA had higher use of steroids (29% vs 15%, P = 0.04) and immunomodulators (40% vs 21%, P = 0.04) at 6 months, higher biologic use at 1 year (34% vs 16%, P = 0.03), earlier first relapse (mean ± SD 29.4 ± 26.1 vs 46.7 ± 43.4 weeks after diagnosis, P = 0.02), and higher colectomy rates by 2 years (21% vs 8%, P = 0.01).

Conclusions:

Children with MA at diagnosis had higher colectomy rates despite earlier treatment escalation and similar baseline severity scores. We identify MA as a promising new prognostic marker in children with newly diagnosed UC.
Venous Thromboembolism Prophylaxis in Pediatric Inflammatory Bowel Disease Patients Hospitalized With a Central Line
Authors: Hamant Laura G. , Gonzalez-llanos Lucia , Patel Ashish S. , McMahon Lisa , Knoll Christine , Swing Ted , Pasternak Brad
Published: February 2023

Objectives:

Patients hospitalized with inflammatory bowel disease (IBD) have increased risk of venous thromboembolism (VTE). The aim of this study was to determine whether the adoption of a VTE protocol would change rates of medical VTE prophylaxis (low molecular weight heparin) in patients with IBD and a central venous catheter (CVC), while subsequently decreasing the incidence of VTE in this population.

Methods:

A protocol for VTE prophylaxis in IBD was established in March of 2018. Every patient hospitalized with an IBD flare and central venous access from March 2013 to March 2020 was identified. Study data, including patient demographics, rates of Doppler ultrasound (US), and rates of VTE were collected using International Classification of Diseases (ICD)-10 codes, CPT codes, and chart review retrospectively. Determination of an IBD flare was based on physician global assessment. Groups were compared with independent-sample t tests and chi-squared tests.

Results:

A total of 313 hospitalizations across 187 different patients were identified that met criteria including IBD and central venous access. VTE prophylaxis increased from 5.24% (n = 12) prior to the intervention to 63.10% (n = 53) after the intervention [chi-square (1, N = 313) = 125.0192, P < 0.001]. Rate of Doppler US increased from 9.17% (n = 21) prior to the intervention to 17.86% (n = 15) after the intervention [chi-square (1, N = 313) = 4.5562, P < 0.05]. Diagnosis of VTE increased from 0.87% (n = 2) prior to the intervention to 7.14% (n = 6) after the intervention [chi-square (1, N = 313) = 9.6992, P < 0.01]. There were no significant differences in the demographic characteristics pre- versus post-intervention.

Conclusions:

Rates of Doppler US and VTE prophylaxis use increased significantly after implementation of a VTE protocol. Rates of VTE diagnosis also increased, though we suspect this may be due to missed diagnoses prior to implementation of the protocol and increased risk awareness after the protocol was established.
Leadership Science in Nursing
Authors: Bacon Cynthia Thornton , Bailey K. David , Caramanica Laura , Losty Lyn Stankiewicz , Nelson-Brantley Heather , Prestia Angela , Snow Francine , Wahl Carol
Published: February 2023

The Association for Leadership Science in Nursing (ALSN) November 2022 International Conference was held at the Frances Payne Bolton School of Nursing at Case Western University. ALSN is dedicated to uniting academic and practice leaders to shape leadership science, education in nursing, and the practice of nursing leadership. One hundred fifty-one nurse leaders from the United States, Canada, and Oman gathered to discuss leadership as highlighted in this column.
To End Workplace Violence, Integrate High-Tech With High-Touch
Authors: Virkstis Katherine , Taylor Jennifer , Bala’ LouAnn
Published: February 2023

A leader should create an environment in which everyone feels safe. Yet, there is a rising, deadly epidemic in healthcare on the heels of the COVID-19 pandemic: workplace violence. Healthcare workers, particularly nurses, are at a far higher risk of violence on the job compared with most other professions. Leaders have the power to reverse this trend by sounding the alarm, doubling down on their commitment to workplace safety organization-wide, and taking a comprehensive approach that integrates high-tech with high-touch strategies.
Success in Supporting Early Mobility and Exercise in a Cardiothoracic Intensive Care Unit
Authors: Marcarian Taline , Obreja Valentina , Murray Katrine , Meltzer Joseph S. , Miller Pamela S.
Published: February 2023

Early mobility contributes to improved patient outcomes and reduced hospital length of stay during acute and intensive care hospitalization. The Bedside Mobility Assessment Tool was implemented in a cardiothoracic intensive care unit during participation in a nationwide evidence-based quality improvement initiative. One outcome included a high level of mobility that was sustained over time. Using the Dynamic Sustainability Framework model, this article describes the key components that contributed to this sustained mobility performance over 4 years.
Effects of Unit Census and Patient Acuity Levels on Discussions During Patient Rounds
Authors: Warren Carly , Chignell Mark , Pinkney Sonia J. , Armstrong Bonnie A. , Guerguerian Anne-Marie , Laussen Peter C. , Trbovich Patricia L.
Published: February 2023

OBJECTIVES:

PICU teams adapt the duration of patient rounding discussions to accommodate varying contextual factors, such as unit census and patient acuity. Although studies establish that shorter discussions can lead to the omission of critical patient information, little is known about how teams adapt their rounding discussions about essential patient topics (i.e., introduction/history, acute clinical status, care plans) in response to changing contexts. To fill this gap, we examined how census and patient acuity impact time spent discussing essential topics during individual patient encounters.

DESIGN:

Observational study.

SETTING:

PICU at a university-affiliated children’s hospital, Toronto, ON, Canada.

SUBJECTS:

Interprofessional morning rounding teams.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We observed 165 individual patient encounters during morning rounds over 10 weeks. Regardless of census or patient acuity, the duration of patient introductions/history did not change. When census was high versus low, acute clinical status discussions significantly decreased for both low acuity patients (00 min:50 s high census; 01 min:39 s low census; –49.5% change) and high acuity patients (01 min:10 s high census; 02 min:02 s low census; –42.6% change). Durations of care plan discussions significantly reduced as a function of census (01 min:19 s high census; 02 min:52 s low census; –54.7% change) for low but not high acuity patients.

CONCLUSIONS:

Under high census and patient acuity levels, rounding teams disproportionately shorten time spent discussing essential patient topics. Of note, while teams preserved time to plan the care for acute patients, they cut care plan discussions of low acuity patients. This study provides needed detail regarding how rounding teams adapt their discussions of essential topics and establishes a foundation for consideration of varying contextual factors in the design of rounding guidelines. As ICUs are challenged with increasing census and patient acuity levels, it is critical that we turn our attention to these contextual aspects and understand how these adaptations impact clinical outcomes to address them.
Contribution of Proteomics in Transplantation: Identification of Injury and Rejection Markers
Authors: Zubair Haseeb , Azim Shafquat , Maluf Daniel G. , Mas Valeria R. , Martins Paulo N.
Published: February 2023

Solid organ transplantation saves thousands of lives suffering from end-stage diseases. Although early transplants experienced acute organ injury, medical breakthroughs, such as tissue typing, and use of immunosuppressive agents have considerably improved graft survival. However, the overall incidence of allograft injury and chronic rejection remains high. Often the clinical manifestations of organ injury or rejection are nonspecific and late. Current requirement for successful organ transplantation is the identification of reliable, accurate, disease-specific, noninvasive methods for the early diagnosis of graft injury or rejection. Development of noninvasive techniques is important to allow routine follow-ups without the discomfort and risks associated with a graft biopsy. Multiple biofluids have been successfully tested for the presence of potential proteomic biomarkers; these include serum, plasma, urine, and whole blood. Kidney transplant research has provided significant evidence to the potential of proteomics-based biomarkers for acute and chronic kidney rejection, delayed graft function, early detection of declining allograft health. Multiple proteins have been implicated as biomarkers; however, recent observations implicate the use of similar canonical pathways and biofunctions associated with graft injury/rejection with altered proteins as potential biomarkers. Unfortunately, the current biomarker studies lack high sensitivity and specificity, adding to the complexity of their utility in the clinical space. In this review, we first describe the high-throughput proteomics technologies and then discuss the outcomes of proteomics profiling studies in the transplantation of several organs. Existing literature provides hope that novel biomarkers will emerge from ongoing efforts and guide physicians in delivering specific therapies to prolong graft survival.
Hannaella floricola sp. nov., a novel basidiomycetous yeast species isolated from a flower of Lantana camara in Portugal
Authors: Aires Andreia , Gonçalves Carla , Sampaio José Paulo
Published: February 2023

During a survey of floricolous yeasts in Portugal, a basidiomycetous yeast representing a novel species in the genus Hannaella was isolated in Portugal from the flower of Lantana camara, an ornamental exotic species native to Central and South America. A combination of phylogenetic analyses of DNA barcode sequences used in yeast molecular systematics, namely the D1/D2 domain and the complete internal transcribed spacer (ITS) region supported the recognition of a new species of Hannaella, that we designate Hannaella floricola sp. nov. (ex-type strain PYCC 9191T=CBS 18097T). Although the assignment of the new species to the genus Hannaella was evident, the detection of its closest relatives appeared more problematic. Nevertheless, our analyses suggested that H. floricola sp. nov. belongs a clade that also includes H. coprosmae, H. oryzae and H. surugaensis, together four candidate novel species. In addition we provide the molecular identification of several unidentified strains whose D1/D2 and ITS sequences are available from GenBank.
The CSF-1R inhibitor Pexidartinib impacts dendritic cell differentiation through inhibition of FLT3 signaling and may antagonize the effect of durvalumab in patients with advanced cancer – results from a phase 1 study
Authors: Voissière Aurélien , Gomez-Roca Carlos , Chabaud Sylvie , Rodriguez Céline , Nkodia Axelle , Berthet Justine , Montane Laure , Bidaux Anne-Sophie , Treilleux Isabelle , Eberst Lauriane , Terret Catherine , Korakis Iphigénie , Garin Gwenaelle , Pérol David , Delord Jean-Pierre , Caux Christophe , Dubois Bertrand , Ménétrier-Caux Christine , Bendriss-Vermare Nathalie , Cassier Philippe A.
Published: February 2023

Tumor-associated macrophages (TAM) are critical determinant of resistance to programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) blockade. This phase I study (MEDIPLEX,NCT02777710) investigated the safety and efficacy of pexidartinib, a CSF-1R-directed tyrosine kinase inhibitor (TKI), and durvalumab (anti-PD-L1) in patients with advanced colorectal (CRC) and pancreatic (PDAC) carcinoma with the aim to enhance responses to PD-L1 blockade by eliminating CSF-1-dependent suppressive TAM. No unexpected toxicities were observed and 2% and 15% of patients achieved partial response and stable disease respectively. Increase of CSF-1 levels and decrease of CD14lowCD16highmonocytes in peripheral blood mononuclear cells (PBMC) confirmed CSF-1R engagement. Treatment significantly decreased blood dendritic cell (DC) subsets and impaired IFN-λ/IL-29 production by type-1 conventional DC inex vivoTLR3-stimulated PBMC. Pexidartinib also targets c-KIT and FLT3, both key growth factor receptors of DC development and maturation. In patients, FLT3-L levels increased with pexidartinib treatment.In vitro, pexidartinib impaired the FLT3-L but not GM-CSF-dependent generation of DC subsets from murine bone marrow progenitors. Our results demonstrate that pexidartinib, through the inhibition of FLT3 signaling, has deleterious effect on DC differentiation, which may explain the limited anti-tumor clinical activity observed in this study. This study suggests that inhibition of FLT3 should be taken into account when combining TKIs with immune checkpoint blockers.

One-sentence summary

Pexidartinib affects the development of dendritic cells
Pattern of Neonatal Outcome of NICU Admissions Born to Teenage Pregnant Women Admitted in a Level-1 Government Hospital from January 2016 to December 2016
Authors: Laurito Arbeen Acosta
Published: February 2023

Teenage pregnancy in the Philippines is increasing and alarming. Services in the antenatal care are in accordance with the Department of Health and the World Health Organization serving pregnant women of all ages. Looking at the post-partum women, we will be identifying factors among this specific teenage group who were considered at risk compared to the older pregnant women.

The researcher aims to conduct a study which can give as baseline clinical picture of the product of conceptions among those teenage pregnant women admitted at Justiniano R. Borja General Hospital.

Among the NCU admitted neonates, 120 (20%) were delivered by teenage pregnant women, 131 (21.83%) from 20-24 years old, and 349 (58.17%) from >25 years old pregnant women.

The prevalence of teenage pregnancy in JRBGH was 20%, with 12 years old as the youngest to have live newborn for 2017. Teenage pregnancy ranges from 20 to 23% on monthly delivery census. While NCU babies born to teenage pregnant women ranges from 10 to 26% on monthly census of NCU admission.

This study found out that teenage pregnancy were significantly different from the 20-24 years old in terms of their parity, timing of first ultrasound and hospital expenses. Other maternal profiles which showed no significant difference were; place of residence, menarche, blood pressure, mode of delivery. Hepatitis B status was described by percentage.

Based on this study, parity is significantly different in both age groups. These study population covered the NCU babies. Repeat pregnancies should be considered seriously to prevent more cases of NCU admission or other morbidities. Post-natal care should be accessed and improved in terms of the ante-natal care, tracking system, local networking of referrals, and more improve access to data and data collection for analysis of existing health programs.

The mean hopital expenses is significantly lower in the teenage pregnant women vs 20-24 years old group. The mean hospital expenses for teenage pregnant women is probably higher because of the study population (neonates) were NCU admitted compared to the total delivery. It is noteworthy to mention that majority of these teenage group (study population) are un-employed. And these hospital expenses may correlates to the out-of-pocket expenses from their families or the cost of LGU funding. Thus, the gross cost of hospitalization from these teenage pregnant women would be Php1,044,357.6 (based on the mean hospital expenses x 88 retrieved SOA) or Php 1,424,124 (based on the mean hospital expenses x 120 teenage pregnant women in NCU), or Php 17,635,402 for 2017 (11,867.7 × 1,486 teenage pregnant deliveries).

There were no significant diffrence noted among the neonatal profile variables, namely; birthweight, Apgar score and outcome (complicated or non-complicated). Length of hospital for mothers and length of NCU stay of neonates were found to be not significant in both age groups.
Genetically Determined Blood Pressure, Antihypertensive Medications, and Risk of Intracranial Aneurysms and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study
Authors: Liu Hanchen , Zuo Huiqin , Johanna Ospel , Zhao Rui , Yang Pengfei , Li Qiang , Lin Xiaolei , Zhou Yu , Liu Jianmin
Published: February 2023

Background

Observational studies suggest that different classes of antihypertensive drugs may have different effects on the occurrence of intracranial aneurysm(IA) and subarachnoid hemorrhage(SAH). However, the reported effects in previous studies are inconsistent, and randomised data are absent. We performed a two-sample Mendelian randomization(MR) analysis to study the causal effects of genetically determined blood pressure(BP) and genetic proxies for antihypertensive drug classes on the risk of IA and SAH.

Methods

Genetic instruments and outcome data were obtained from independent genome-wide association studies(GWAS) or published data, which were exclusively restricted to european ancestry. Causal relationships were identified using inverse-variance weighted MR analyses and a series of statistical sensitivity analyses. The Finngen consortium was used for repeated analysis to verify results obtained from above GWAS.

Results

Two-sample MR analysis showed that genetically determined Systolic BP, Dystolic BP and Pulse Pressure were related to higher risk of IA and SAH. Based on indentified single nucleotide polymorphisms (SNPs) that influence the effect of calcium channel blockers (CCB, 43 SNPs), beta-blockers (BB, 30 SNPs), angiotensin-converting enzyme inhibitors (ACEI, 16 SNPs), angiotensin receptor blockers (ARB, 11 SNPs), and thiazides (5 SNPs), genetically determined effect of CCBs was associated with higher risk of IA (OR, 1.08 [95%CI, 1.04-1.12], P=1.21×10-5) and SAH (OR, 1.07 [95%CI, 1.02-1.12], P=2.05×10-3). No associations were found between other antihypertensive drugs and risk of IA or SAH. The effect of CCBs on SAH was confirmed in Finngen consortium samples(OR, 1.04 [95%CI, 1.00-1.08], P=0.042).

Conclusion

This MR analysis supports the protection effect of hypertension control on the occurrence of intracranial aneurysm and subarachnoid hemorrhage. However, genetic proxies for calcium channel blockers were associated with increased risk of intracranial aneurysm and subarachnoid hemorrhage. Further studies are required to confirm these findings and investigate the underlying mechanisms.
Analysis of sex disparities in under-five mortality rates in Ghana: Insights from vector autoregressive modeling
Authors: Essel Nana Owusu , Appiah Simon Kojo , Mensah Isaac Adjei
Published: February 2023

International monitoring organizations call for child mortality indicators to be disaggregated by gender. However, there remains a paucity of studies, especially, from the sub-Saharan region aimed at producing accurate forecasts of child mortality indicators with their sex variations. This study aims at investigating disparities in indicators of childhood mortality rates by sex in Ghana by employing vector autoregressive (VAR) model to analyze jointly annual recorded data on total, male and female under-five mortality rates (TU5MR, MU5MR, FU5MR, respectively). The results show gradual declining under-five mortality trends among sexes in both the historical and forecasted rates. The trivariate traditional and instantaneous Granger causality analyses found that any of the mortality indicators Granger causes the other two combinations, except TU5MR to MU5MR and FU5MR. The forecast error variance decomposition analyses revealed that FU5MR was the most exogenous variable while long-term impulse response function analyses indicated that unit shocks in FU5MR significantly increased TU5MR. The VAR(2) model forecast constructed revealed that contrary to recent predictions based on wider interval data derived from demographic health surveys, Ghana may meet the SDG 3.2.2 if ongoing efforts are sustained and that focusing policies and interventions on reducing FU5MR would largely contribute to reducing TU5MR in Ghana.

Ethical considerations

Not applicable. This study did not require ethics approval or consent for participation.
The Impact of COVID-19 on Cancer Screening and Treatment in Older Adults: The Multiethnic Cohort Study
Authors: Mak Victoria P. , White Kami , Wilkens Lynne R. , Cheng Iona , Haiman Christopher , Marchand Loïc Le
Published: February 2023

Background

The Coronavirus Disease of 2019 (COVID-19) has impacted the health and day-to-day life of individuals, especially the elderly and people with certain pre-existing medical conditions, including cancer. The purpose of this study was to investigate how COVID-19 impacted access to cancer screenings and treatment, by studying the participants in the Multiethnic Cohort (MEC) study.

Methods

The MEC has been following over 215,000 residents of Hawai’i and Los Angeles for the development of cancer and other chronic diseases since 1993-1996. It includes men and women of five racial and ethnic groups: African American, Japanese American, Latino, Native Hawaiian, and White. In 2020, surviving participants were sent an invitation to complete an online survey on the impact of COVID-19 on their daily life activities, including adherence to cancer screening and treatment. Approximately 7,000 MEC participants responded. A cross-sectional analysis was performed to investigate the relationships between the postponement of regular health care visits and cancer screening procedures or treatment with race and ethnicity, age, education, and comorbidity.

Results

Women with more education, women with lung disease, COPD, or asthma, and women and men diagnosed with cancer in the past 5 years were more likely to postpone any cancer screening test/procedure due to the COVID-19 pandemic. Groups less likely to postpone cancer screening included older women compared to younger women and Japanese American men and women compared to White men and women.

Conclusions

This study revealed specific associations of race/ethnicity, age, education level, and comorbidities with the cancer-related screening and healthcare of MEC participants during the COVID-19 pandemic. Increased monitoring of patients in high-risk groups for cancer and other diseases is of the utmost importance as the chance of undiagnosed cases or poor prognosis is increased as a result of delayed screening and treatment.

Funding

This research was partially supported by the Omidyar ‘Ohana Foundation and grant U01 CA164973 from the National Cancer Institute.
Adaptive nutrition intervention stabilizes serum phosphorus levels in hemodialysis patients: a multi-center decentralized clinical trial using real-world data
Authors: Chung Moon Kyung , Kim Do Hyoung , Park Ji In , Lee Sunhwa , Park Hayne Cho , Kim Kyungmin , Kang Young Sun , Ko Kangji , Kim Jieun , Koo Hoseok , Cha Jin Joo , Kwon Young Eun , Kim Ju Han
Published: February 2023

Objective

This study aims to evaluate the effect of an adaptive nutritional and educational intervention for hemodialysis patients in a routine care setting, using real-world data from electronic health records.

Methods

Decentralized clinical trial of seven hemodialysis facilities recruited patients under hemodialysis for over 3 months (N=153) for an 8-week adaptive intervention protocol and divided them into four groups: (1) control (2) education intervention (3) meal intervention (4) education and meal interventions. Educational contents are digitally delivered via mobile phones and pre-made meals tailored on laboratory findings via home delivery. Changes in serum electrolytes and malnutrition inflammation score (MIS) are analyzed.

Results

Meal intervention statistically significantly stabilized serum phosphorus level (β = −0.81) at week 8 with increased likelihood of being in normal range (Odds ratio = 1.21). Meal and education group showed better nutritional status (MIS=3.97) than the control group (MIS=4.57) at week 8 (adjusted p<0.05). No significant changes were observed in serum potassium level, depression, and self-efficacy.

Conclusion

It is demonstrated that an adaptive education and meal interventions in a real-world care setting may benefit hemodialysis patients’ serum phosphorus control and nutritional status, without negative effect on depression levels or self-efficacy.
Effects of a Telehealth-Delivered Mediterranean Diet Intervention in Adults with Rheumatoid Arthritis (MEDRA): A Randomised Controlled Trial
Authors: Raad Tala , George Elena , Griffin Anne , Larkin Louise , Fraser Alexander , Kennedy Norelee , Tierney Audrey
Published: February 2023

Objective

To compare the effects a Mediterranean diet (MedDiet) versus the Irish Healthy Eating Guidelines (HEG) on physical function and quality of life in adults with rheumatoid arthritis (RA) in Ireland.

Methods

Forty-four adults with RA were randomised (1:1) to the MedDiet or HEG for 12 weeks. The intervention included three video teleconsultations and two follow-up telephone calls facilitated by a Registered Dietitian (RD). Changes in physical function by Health Assessment Questionnaire-Disability Index (HAQ-DI) and quality of life by Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) were the primary outcomes measured. Secondary outcomes included changes in dietary adherence, physical activity by Yale Physical Activity survey (YPAS), patient-perceived pain and general health, and anthropometric measures. All measurements were administered at baseline and repeated at 6 and 12 weeks.

Results

Forty participants completed the study. Participants were primarily females (87.5%), mean age was 47.5 ± 10.9 years. At the end of the intervention, participants in the MedDiet group reported significantly better physical function (p=0.006) and quality of life (p=0.037) compared to HEG group. From baseline to 12 weeks, physical function significantly improved in both die tgroups, MedDiet (0.9 ± 0.5 to 0.5 ± 0.4 units, p <0.001) and HEG (1.4 ± 0.7 to 1.0 ± 0.6 units, p<0.001). Quality of life also significantly improved in the MedDiet (10.1 ±7.5 to 4.0 ± 4.7 units, p<0.001) and HEG group (11.25 ±7.2 to 7.9 ±6.4 units, p=0.048). Physical activity improved significantly in the MedDiet (56.7 ±28.6 to 70.6±33.5 points, p=0.01) but not within the HEG group despite similar recommendations.

Conclusion

Adhering to the MedDiet and Irish Healthy Eating Guidelines resulted in improvements in RA patient-reported outcomes. The changes observed in both diet groups are likely due to the improvement in overall diet quality irrespective of dietary prescription.

Trial registration number

NCT04262505
Preparation for cardiac procedures: identifying gaps between outpatients’ views and experiences of patient-centred care
Authors: Fakes Kristy , Williams Trent , Collins Nicholas , Boyle Andrew , Sverdlov Aaron L , Boyes Allison , Sanson-Fisher Rob
Published: February 2023

Background

To examine the delivery of patient-centred care and identify any gaps in care perceived as essential by patients; this study examined outpatients’: 1) views on what characterises essential care and 2) experiences of care received, in relation to cardiac catheterisation and subsequent cardiovascular procedures.

Methods

A cross-sectional descriptive study was undertaken. Surveys were posted to outpatients who had undergone elective cardiac catheterisation in the prior six months at an Australian tertiary public hospital. Participants completed a 65-item survey to determine: a) aspects of care they perceive as essential for a healthcare team to provide to patients receiving care for a cardiac condition (Important Care Survey); or b) their actual care received (Actual Care Survey). Numbers and percentages were used to calculate the most frequently identified essential care items by patients; and the experiences of care received. Items rated as either ‘Essential’ or ‘Very important’ by at least 80% of participants were determined, reflecting patient endorsement of the importance of the component of care. A gap in patient-centred care was identified as being any item that was endorsed as essential/very important by 80% or more of participants but reported as received by less than 80% of participants.

Results

Of 582 eligible patients, 264 (45%) returned a completed survey. 43/65 items were endorsed by over 80% of participants as essential/very important. Of those, for 22 items, less than 80% of respondents reported the care as received. Gaps were identified in relation to GP consultation (3 items), preparation (4 items), having the procedure (2 items), follow-up care (1 item), subsequent decision making for treatment (4 items), prognosis (6 items) and post-treatment follow-up (1 item).

Conclusions

Areas were identified where actual care fell short of patients’ perceptions of essential care, particularly general practitioner involvement, the referral process and information on patient prognosis.
Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans
Authors: Kop Benjamin R. , Oghli Yazan Shamli , Grippe Talyta C. , Nandi Tulika , Lefkes Judith , Meijer Sjoerd W. , Farboud Soha , Engels Marwan , Hamani Michelle , Null Melissa , Radetz Angela , Hassan Umair , Darmani Ghazaleh , Chetverikov Andrey , den Ouden Hanneke E.M. , Bergmann Til Ole , Chen Robert , Verhagen Lennart
Published: February 2023

Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Further, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Further, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.
Structural brain correlates of non-verbal cognitive ability in 5-year-old children: findings from the FinnBrain Birth Cohort study
Authors: Pulli Elmo P. , Nolvi Saara , Eskola Eeva , Nordenswan Elisabeth , Holmberg Eeva , Copeland Anni , Kumpulainen Venla , Silver Eero , Merisaari Harri , Saunavaara Jani , Parkkola Riitta , Lähdesmäki Tuire , Saukko Ekaterina , Kataja Eeva-Leena , Korja Riikka , Karlsson Linnea , Karlsson Hasse , Tuulari Jetro J.
Published: February 2023

Non-verbal cognitive ability predicts multiple important life outcomes, e.g., school and job performance. It has been associated with parieto–frontal cortical anatomy in prior studies in adult and adolescent populations, while young children have received relatively little attention. We explored the associations between cortical anatomy and non-verbal cognitive ability in 165 5-year-old participants (mean scan age 5.40 years, SD 0.13; 90 males) from the FinnBrain Birth Cohort study. T1-weighted brain magnetic resonance images were processed using FreeSurfer. Non-verbal cognitive ability was measured using the Performance Intelligence Quotient (PIQ) estimated from the Block Design and Matrix Reasoning subtests from the Wechsler Preschool And Primary Scale Of Intelligence (WPPSI-III). In vertex-wise general linear models, PIQ scores associated positively with volumes in left caudal middle frontal and right pericalcarine regions, as well as surface area in left caudal middle frontal, left inferior temporal, and right lingual regions. There were no associations between PIQ and cortical thickness. To the best of our knowledge, this is the first study to examine structural correlates of non-verbal cognitive ability in a large sample of typically developing 5-year-olds. The findings are generally in line with prior findings from older age groups.
IMD-mediated innate immune priming increases Drosophila survival and reduces pathogen transmission
Authors: Prakash Arun , Fenner Florence , Shit Biswajit , Salminen Tiina S. , Monteith Katy M. , Khan Imroze , Vale Pedro F.
Published: February 2023

Invertebrates lack the immune machinery underlying vertebrate-like acquired immunity. However, in many insects past infection by the same pathogen can ‘prime’ the immune response, resulting in improved survival upon reinfection. Here, we investigated the generality, specificity and mechanistic basis of innate immune priming in the fruit flyDrosophila melanogasterwhen infected with the gram-negative bacterial pathogenProvidencia rettgeri. We find that priming in response toP. rettgeriinfection is a long-lasting and pathogen-specific response. We further explore the epidemiological consequences of immune priming and find it has the potential to curtail pathogen transmission by reducing pathogen shedding and spread. The enhanced survival of individuals previously exposed to a non-lethal bacterial inoculum coincided with a transient decrease in bacterial loads, and we provide strong evidence that the effect of priming requires the IMD-responsive antimicrobial-peptideDiptericin-Bin the fat body. Further, we show that whileDiptericin Bis the main effector of bacterial clearance, it is not sufficient for immune priming, which requires regulation of IMD by peptidoglycan recognition proteins. This work underscores the plasticity and complexity of invertebrate responses to infection, providing novel experimental evidence for the effects of innate immune priming on population-level epidemiological outcomes.
Inhibition of cleavage of human complement component C5 and the R885H C5 variant by two distinct high affinity anti-C5 nanobodies
Authors: Struijf Eva M. , De la O Becerra Karla I , Ruyken Maartje , van Oosterom Fleur , Siere Danique Y. , Heesterbeek Dani A. C. , Dolk Edward , Heukers Raimond , Bardoel Bart W. , Gros Piet , Rooijakkers Suzan H.M.
Published: February 2023

The human complement system plays a crucial role in immune defense. However, its erroneous activation contributes to many serious inflammatory diseases. Since most unwanted complement effector functions result from C5 cleavage, development of C5 inhibitors, such as clinically approved monoclonal antibody Eculizumab, are of great interest. In this study, we developed and characterized two anti-C5 nanobodies, UNbC5-1 and UNbC5-2. Using surface plasmon resonance (SPR), we determined a binding affinity of 120 pM for UNbC5-1 and 8 pM for UNbC5-2. Competition experiments determined that the two nanobodies recognize distinct epitopes on C5. Both nanobodies efficiently interfered with C5 cleavage in a human serum environment, as they prevented red blood cell lysis via membrane attack complexes (C5b-9) and the formation of chemoattractant C5a. The cryo-EM structure of UNbC5-1 and UNbC5-2 in complex with C5 revealed that the binding interfaces of UNbC5-1 and UNbC5-2 overlap with known complement inhibitors Eculizumab and RaCI3, respectively. UNbC5-1 binds to the MG7 domain of C5, facilitated by a hydrophobic core and polar interactions, and UNbC5-2 interacts with the C5d domain mostly by salt bridges and hydrogen bonds. Interestingly, UNbC5-1 potently binds and inhibits C5 R885H, a genetic variant of C5, that is not recognized by Eculizumab. Altogether, we identified and characterized two different, high affinity nanobodies against human C5. Both nanobodies could serve as diagnostic and/or research tools to detect C5 or inhibit C5 cleavage. Furthermore, the residues targeted by UNbC5-1 hold important information for therapeutic inhibition of different polymorphic variants of C5.