bluuebunny/crossref_metadata_2025 huggingface dataset:
THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE IS NOT RECOMMENDED FOR THE TREATMENT OF LARGE MACULAR HOLES SMALLER THAN 650 µm
Authors: Chen Junhong , Tao Jiwei , Zhang Yun
Published: August 2024

Purpose:

To compare the anatomical and functional outcomes of the inverted flap technique versus conventional internal limited membrane (ILM) peeling in large idiopathic full-thickness macular holes <650 µm.

Methods:

Retrospective comparative study. Patients with large idiopathic macular holes <650 µm who underwent either the inverted ILM flap technique (IFT) or the ILM peeling were investigated. The main outcomes included the macular hole closure rate, recovery rates of the external limiting membrane and ellipsoid zone, and best-corrected visual acuity at 1, 3, and 6 months postoperatively.

Results:

Sixty-nine eyes of 69 patients who underwent the IFT (n = 32, Group A) or ILM peeling (n = 37, Group B) were included. In both groups, a significant best-corrected visual acuity improvement was acquired throughout the follow-up period. The mean best-corrected visual acuity increased at each follow-up visit in both groups (P < 0.001). However, the IFT group showed poorer visual results than the ILM peeling group at all time points (P = 0.039, 0.005, 0.006). The external limiting membrane recovery rate in the ILM peeling group (78.3%, 29/37 eyes) was higher than that in the IFT group (53.1%, 17/32 eyes) at 6 months after surgery (P = 0.079).

Conclusion:

The IFT resulted in poorer external limiting membrane and visual recovery than ILM peeling, suggesting that the IFT is not a suitable option for repairing large macular holes <650 µm.
COMPARISON OF SURGICAL OUTCOMES OF MACULAR TELANGIECTASIA TYPE 2–ASSOCIATED MACULAR HOLE WITH IDIOPATHIC MACULAR HOLE
Authors: Lee Ji Hye , Kim Joo-Young , Hwang Bo-Een , Kim JU-Young , Kim Rae-Young , Kim Mirinae , Park Young-Gun , Park Young-Hoon
Published: August 2024

Purpose:

To assess the longitudinal surgical outcomes of macular telangiectasia Type 2 macular hole (MacTel-MH) and compare them with those of idiopathic MH.

Methods:

This retrospective, single-tertiary center study included patients who underwent MH surgery between January 2015 and September 2023. Patients with characteristic optical coherence tomography findings of MacTel in both eyes or those who underwent fluorescence angiography were classified as having MacTel MH. Baseline and postoperative best-corrected visual acuity and optical coherence tomography parameters were reviewed.

Results:

Totally, 27 and 243 eyes with MacTel and idiopathic MH, respectively, were included. Macular hole closure rate was better achieved in idiopathic than in MacTel MH group at two years postoperatively. Temporal recovery of ellipsoid zone and external limiting membrane was more prominent in MacTel than in idiopathic MH group. Statistically significant visual acuity improvement was seen between three months and two years postoperatively in MacTel MH group.

Conclusion:

To the best of our knowledge, this is the first study to analyze the surgical outcomes of MacTel MH in both anatomical and functional aspects and compare them with patients with idiopathic MH. Postoperative microglia change would have affected the restoration of outer retinal layer of patients; however, further studies are needed for clarification.
Frailty Assessment Scale for Heart Failure
Authors: Chao Ying-Cheng , Liu Chieh-Yu , Hung Huei-Fong , Lee Chii-Ming , Hsu Shu-Pen , Chiou Ai-Fu
Published: August 2024

Background

Frailty is common in patients with heart failure. Specific scales, including the Clinical Frailty Scale, exist but have not undergone thorough psychometric validation among patients with heart failure.

Objective

The aim of this study was to develop and validate the Frailty Assessment Scale for Heart Failure (FAS-HF) in patients with heart failure.

Methods

This study included 3 phases. In phase I, conceptualization and item generation, the FAS-HF was initially developed through the analysis of qualitative research data and a literature review. In phase II, item selection and content validity, the Delphi method was used to gather experts' opinions and suggestions regarding the FAS-HF. In phase III, field testing and psychometric evaluation, a cross-sectional study of 184 patients with heart failure in northern Taiwan was conducted to test the reliability and validity of the FAS-HF.

Results

The 15-item FAS-HF included the physical, psychological, and social frailty domains. The total score ranged from 0 to 45, with higher scores representing frailer individuals. Exploratory factor analysis revealed that the cumulative loading variance was 57.39%. In the confirmatory factor analysis, the goodness-of-fit index (0.91), adjusted goodness-of-fit index (0.87), and root mean square error of approximation (0.06) were acceptable for model fit. Acceptable reliability was found, with a Cronbach α coefficient of 0.87 and a test-retest reliability of 0.99. Compared with the Fried frailty phenotype, the area under the receiver operating characteristic curve was 0.94, and the optimal cutoff score for frailty was 20.

Conclusions

The FAS-HF has good reliability, validity, and discrimination and can be used as a frailty indicator for patients with heart failure.
When Sexual Violence Goes Viral
Authors: Vallée-Ouimet Sandrine , Pariseau-Legault Pierre , Labrecque-Lebeau Lisandre
Published: August 2024

Since the popularization of the #MeToo movement, the prevention and management of sexual violence (SV) has become prominent in North American public discourse, including in the province of Québec (Canada). Despite such an important visibility in the public sphere, there is little scientific evidence of how nursing practice has adapted to the popularization of the #MeToo movement, led by victims of SV. Drawing on critical feminist theories, we describe the results from a literature review on nursing practice in the context of SV on college and university campuses since the #MeToo movement. A literature search was performed in five databases using keywords targeting nursing practice in the context of SV. In total, 45 articles were selected for analysis. Eight studies were added for their relevance (obtained outside the databases). Next, a reflexive thematic analysis inspired by Braun and Clarke (2006) was conducted. The literature review was then used to compare current practices in Québec. The results identify the persistence of numerous myths and stereotypes that contribute negatively to the credibility of persons experiencing SV. The results also describe the difficulty of public institutions to change structures aimed at preventing and managing SV in response to the popularization of the #MeToo movement. The results indicate the relevance of using an intersectional feminist theoretical framework to better understand the complexities of SV. Through our analysis, we show that, more than ever, the evolution of forensic nursing practice must be informed by political and testimonial activism driven by persons experiencing SV.
The Impact of Patients and Student Mental Health Nurses Sharing Time Together in Forensic Units
Authors: Jones Emma S. , Wright Karen M. , McKeown Mick
Published: August 2024

Student mental health nurses have greater patient contact than registered nurses, and this is appreciated by patients. This phenomenological study explored the impact of patients and student mental health nurses' time shared on forensic units for men carrying a personality disorder diagnosis. Phenomenology was the underpinning philosophy of this research. Patients and student mental health nurses in forensic hospitals participated in unstructured hermeneutic interviews. The time students and patients shared together was considered a gift, enabling them to feel that they were “just people” and valued, strongly impacting on their sense of person. The impact the students have on patients' quality of life is meaningful. When the students and patients connected, it had powerful implications for their sense of humanness and value, highlighting the reciprocal impact they each have on another and the importance of having student nurse clinical placements in forensic wards and facilities.

Implications for Clinical Forensic Nursing Practice: This article offers a unique contribution to forensic practice by exploring the experiences of the time patients and students share together in forensic units. Students, who often have the greatest contact with patients, represent the present and future of nursing, and their time is appreciated by patients. Previous research focuses on attitudes and therapeutic relationships, rather than the impact of shared contact. In addition to this, patients in forensic services with personality disorder diagnoses can be the most stigmatized group in mental health care, and exploration of their experiences is lacking. These experiences must be shared.
Organizational and Individual Contributing Factors to Safety Climate in Healthcare Industries—Bayesian Network Predictive Modeling Approach
Authors: He Yimin , Lee Jin , Huang Yueng-Hsiang , Hu Changya
Published: August 2024

Objectives

The current study aims to identify individual and joint drivers that significantly influence the safety climate in healthcare industries by using Bayesian network (BN) simulations for an in-depth analysis.

Methods

Survey data were collected from 452 employees from two branches of one hospital in China for a study about workplace safety. The original English surveys were translated into Chinese using the back-translation procedure recommended by Brislin. Employees were asked to complete two online surveys with 1 month in between each administration. The sample was 42% doctors and 58% nurses. A BN model, based on theory, was updated and complemented with expert knowledge. A graphical model based on expert knowledge and data-driven machine learning approaches was used to refine the BN structure, representing interrelationships among all studied variables. The BN model was employed to identify the best key drivers and joint strategies for safety climate improvement.

Results

The BN model demonstrated a good overall fit. The Euclidean distance metric was used to assess the influence between connected variables, with interpersonal trust and locus of control having the strongest independent effects on safety climate among the five contributing factors. Joint strategies, particularly joint optimization of error disclosure culture and interpersonal trust, as well as error disclosure culture and self-efficacy, were most effective in promoting a safe climate.

Conclusions

The findings suggest that hospital safety climate can be improved by providing a psychologically safe error disclosure culture and enhancing interpersonal trust among employees and their self-efficacy.
Engineering a Microsurgical Training Tool for Vasectomy Reversals
Authors: Alver Charles G. , Codrington Jason M. , Tradewell Michael B. , Ramasamy Ranjith , Agarwal Ashutosh
Published: August 2024

We describe the development of an elastomer-molded vas model as a microsurgical training tool, particularly for vasectomy reversals. This microsurgical training tool is formed by molding polydimethylsiloxane into a vas deferens shape with a patent lumen through the use of a 3D printed mold and simple monofilament wires. The expanded use of our vas model as a microsurgical training tool will allow urologists in training to improve and develop their microsurgical skills outside of patient caseloads and without the need for extensive cadaveric or animal model practice.
Extended Duration of Impella 5.5 Support Does Not Adversely Impact Outcomes Following Heart Transplantation: A National Registry Analysis
Authors: Hong Yeahwa , Dorken-Gallastegi Ander , Nasim Umar , Hess Nicholas R. , Ziegler Luke A. , Abdullah Mohamed , Iyanna Nidhi , Ramanan Raj , Hickey Gavin W. , Kaczorowski David J.
Published: August 2024

Prior studies assessing the effects of Impella 5.5 support duration on posttransplant outcomes have been limited to single-center case reports and series. This study evaluates the impact of Impella 5.5 support duration on outcomes following heart transplantation using the United Network for Organ Sharing database. Adult heart transplant recipients who were directly bridged to primary isolated heart transplantation with Impella 5.5 were included. The cohort was stratified into two groups based on the duration of Impella support: less than or equal to 14 and greater than 14 days. The primary outcome was 90 day posttransplant survival. Propensity score matching was performed. Sub-analysis was conducted to evaluate the impact of greater than 30 days of Impella support on 90 day survival. Three hundred thirty-two recipients were analyzed. Of these, 212 recipients (63.9%) were directly bridged to heart transplantation with an Impella support duration of greater than 14 days. The two groups had comparable 90 day posttransplant survival and complication rates. The comparable posttransplant survival persisted in a propensity score-matched comparison. In the sub-analysis, Impella support duration of greater than or equal to 30 days did not adversely impact 90 day survival. This study demonstrates that extended duration of support with Impella 5.5 as a bridge to transplantation does not adversely impact posttransplant outcomes. Impella 5.5 is a safe and effective bridging modality to heart transplantation.
Development and Validation of a Novel Pediatric Mechanical Circulatory Support Risk Stratification Tool: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Ventricular Assist Device Score
Authors: Bonilla-Ramirez Carlos , Lorts Angela , Spinner Joseph A. , Wright Lydia , Niebler Robert A. , Peng David M. , Davies Ryan R. , Rosenthal David N. , O’Connor Matthew J.
Published: August 2024

We sought to develop and validate a new risk stratification score for mortality for children supported with a ventricular assist device (VAD). This retrospective, multicenter study used data from patients undergoing VAD implantation between April 2018 and February 2023 at 44 participating institutions in the Advanced Cardiac Therapies Improving Outcomes (ACTION) network. Multivariable Cox proportional-hazards modeled mortality after VAD implantation. A total of 1,022 patients were enrolled. The 1 year mortality was 19% (95% confidence interval [CI]: 16–23). The multivariable model was used to build the ACTION VADs risk stratification score with four components: ventilation, advanced organ support (dialysis or ECMO), diagnosis, and size (weight ≤5 kg). One point is added for each risk factor. Based on the sum of the risk factors, patients were classified into four classes: class 0—green (4% mortality at 1 year), class 1—yellow (16% mortality at 1 year), class 2—orange (21% mortality at 1 year), and class 3 or higher—red (42% mortality at 1 year). The score performed well, with area under the curve (AUC) of 0.72 and excellent calibration. The ACTION VADs score for mortality can be calculated easily and offers risk stratification and prognostic information for pediatric VAD candidates. This is the first validated risk assessment tool for pediatric mechanical circulatory support.
Implications of frailty before and after intensive care unit admission
Authors: Gordon Joshua I. , Brummel Nathan E.
Published: August 2024

Purpose of review

In the decade since the first publications related to frailty in those with critical illness, the study of frailty has rapidly increased. The purpose of this review is to update the reader on recent advances across several important areas of frailty research: how best to identify frailty in those with critical illness, studies describing the relationship between frailty and delirium, and how frailty affects outcomes for those with coronavirus disease 2019 (COVID-19), which, despite rates and severity of acute infection declining, still tremendously impacts patients long after the acute infection, resulting in symptoms of long COVID-19.

Recent findings

A number of frailty assessment tools exist, to date, the Clinical Frailty Scale based on the deficit accumulation approach to defining frailty, is the most commonly used in ICU studies. Several novel frailty instruments for the ICU are being developed. Because tools assessing frailty by the phenotypic and deficit accumulation approaches identify different populations, careful choice of a frailty assessment tool is warranted.

Frailty and delirium are hypothesized to represent different clinical expressions of a similar underlying vulnerability, thus identifying frailty may be a useful means by which to identify patients at high risk of becoming delirious. Recent studies show that frailty at ICU admission is a predictor of the development of delirium.

Finally, frailty and its outcomes were studied in patients with COVID-19. As with other causes of critical illness, frailty was highly prevalent in those admitted to the ICU and is associated with greater mortality. Frailty was also associated with increased decisions to limit life support treatments, but these decisions were not different among those admitted with COVID-19 or for other reasons.

Frailty in those with critical illness is an emerging field of study. Future work to define the optimal means by which to identify this syndrome and how best to manage critically ill patients with frailty are needed.
Progress in physiologically based pharmacokinetic-pharmacodynamic models of amino acids in humans
Authors: McColl Taylor J. , Clarke David C.
Published: August 2024

Purpose of review

Amino acids are critical to health, serving both as constituents of proteins and in signaling and metabolism. Amino acids are consumed as nutrients, supplements, and nutraceuticals. Much remains to be learned about amino acid function. Physiologically based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling is an emerging tool for studying their complex biology. This review highlights recent PBPK-PD models developed to study amino acid physiology and metabolism and discusses their potential for addressing unresolved questions in the field.

Recent findings

PBPK-PD models provided several insights. They revealed the interplay between the mechanisms by which leucine governs skeletal muscle protein metabolism in healthy adults. The models also identified optimal dosing regimens of amino acid supplementation to treat sickle-cell disease and recurrent hypoglycemia, and to minimize drug side effects in seizure disorders. Additionally, they characterized the effects of novel anticancer drugs that seek to deprive cancer cells of amino acids. Future models may inform treatment strategies for sarcopenia, characterize distinctions between animal- and plant-based nutrition, and inform nutrient-drug interactions in Parkinson's disease.

PBPK-PD models are powerful tools for studying amino acid physiology and metabolism, with applications to nutrition, pharmacology, and their interplay.
Regurgitation, eructation, and supragastric belch: retrograde esophageal motility, disorders, and treatment
Authors: Patel Pooja , Layne Sabrina , Leiman David A.
Published: August 2024

Purpose of review

This review describes pathologic conditions of retrograde flow into the esophagus along with recent therapeutic advances and treatment options.

Recent findings

The esophagus facilitates anterograde and retrograde movement of contents, the latter of which is mediated by transient lower esophageal sphincter relaxations (TLESRs). Gastroesophageal reflux disease (GERD) often includes esophageal-specific symptoms such as heartburn or regurgitation. Volume regurgitation responds less frequently to acid suppression with proton pump inhibitors (PPIs) than heartburn, given its relationship with incompetence of the esophagogastric junction (EGJ) and increased frequency of TLESRs. Therefore, although the refluxate pH can be altered with PPIs, the frequency of reflux episodes is generally not reduced and surgical and endoscopic treatments may be favored. Other instances of abnormal retrograde esophageal flow respond better to medical therapy, or lifestyle interventions. Compared to gastric belching because of increased stomach distension, supragastric belching is caused by intake of air from pharynx into the esophagus followed by rapid expulsion of air. These conditions can be distinguished on esophageal tests such as high-resolution manometry and are likely to respond to behavioral modifications.

Retrograde flow into the esophagus can be a normal occurrence, but diagnostic testing to distinguish causes can guide appropriate intervention.
The Brussels Breast Surgery Fellowship | A Three-Month Experience in Advancing Skills in Breast Surgery
Authors: Kyriazidis Ioannis
Published: August 2024

The Brussels Breast Surgery Fellowship at Brussels University Hospital offers a unique 3-month clinical immersion in reconstructive and aesthetic breast surgery. Under the guidance of fellowship director Prof. Moustapha Hamdi and his esteemed colleagues, the fellow is exposed to a high volume and wide breadth of cases spanning autologous and implant-based breast reconstruction, oncoplastic surgery, breast reduction and mastopexy, implant augmentation, revision breast surgery, and fat grafting. The multidisciplinary team approach, involving close collaboration with breast surgeons, provides valuable experience in oncoplastic planning and execution. In addition to time in the operating theater, the fellow gains knowledge through outpatient clinics, didactic teaching sessions, and clinical research opportunities leveraging the department's extensive prospective database. As the 2023 fellowship awardee, I had the privilege of learning directly from Prof. Dr. Moustapha Hamdi and participating in over 130 cases across the reconstructive and aesthetic spectrum. Unique features of the fellowship included exposure to lymphedema surgery utilizing the Symani robotic system, advanced techniques like the internal bra, volume distribution mastopexies, observation of private aesthetic clinic cases, and optional participation in academic workshops. This fellowship represents an outstanding opportunity to refine one's skills in breast surgery and microsurgery while experiencing the rich culture of Belgium.
Does Inter-Eye Asymmetry of Disc Area Explain Differences in Onset of Nonarteritic Anterior Ischemic Optic Neuropathy?
Authors: Singh Shonar , Guillot Florian H. , Henderson Amanda D. , Carey Andrew R.
Published: August 2024

Background:

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in individuals over the age of 50 years. It is associated with conventional vascular risk factors and structural vulnerabilities including “disc-at-risk.” We aim to ascertain if a correlation exists between optic nerve head size and the onset of NAION.

Methods:

We performed a retrospective chart review of patients with an ICD-10 diagnosis of unilateral or bilateral NAION who underwent optical coherence tomography (OCT) and visual field testing. The primary outcome measure was the disc area as measured on OCT at a follow-up (minimum 6 months after acute vision loss) of the involved (or first involved for bilateral cases) vs fellow eye. The secondary outcome was the cup-to-disc ratio (CDR) of the first vs fellow eye.

Results:

Seventy-three patients were included, of which 58 (79%) had unilateral and 15 (21%) had bilateral NAION, with a median follow-up of 23 months. Between the first eye involved and the fellow eye, there were no statistically significant differences in the mean disc area (1.69 ± 0.29 vs 1.71 ± 0.29, P = 0.7). However, average CDR (0.41 ± 0.20 vs 0.28 ± 0.18, P < 0.001) and vertical CDR (0.42 ± 0.20 vs 0.28 ± 0.19, P < 0.0001) were significantly larger in the involved eye.

Conclusions:

Despite no statistically significant differences in the disc area between the affected eye and the fellow eye, CDR was larger in eyes with a history of NAION compared with fellow eyes. Further research is required to elucidate local factors that may increase the risk of NAION in one eye relative to the other.
Aspergillus esophagitis in a patient with solid tumors: a case report
Authors: Abi Rached Vanessa , Azar Karine , Gerges Sarah , Hallit Souheil , Akoury Elie , Chahine Georges , Hallit Rabih , Akiki Bassem , Rizk Rita
Published: August 2024

Esophageal aspergillosis is a rare occurrence primarily documented in hematologic malignancies, and only rarely occurring among patients with solid tumors. In this case report, we present the unique case of an 81-year-old Lebanese man who had a remarkable medical history, including four solid tumors. The patient sought medical attention due to dysphagia and weight loss, prompting a gastroscopic examination that revealed a necrotic abscess at the esophagogastric junction. Initial treatment with fluconazole and esomeprazole was administered, but the recurrence of similar symptoms led to a repeat gastroscopy, unveiling a diagnosis of Aspergillus esophagitis. Intravenous voriconazole was promptly initiated; however, the patient developed a significant pericardial effusion and expired, with Aspergillus species identified in the pericardial fluid prior to patient expiring. This exceptional case emphasizes the importance of considering esophageal aspergillosis in cancer patients who present with refractory symptoms such as epigastric pain, dysphagia, nausea, and vomiting, despite symptomatic treatment. Our findings underscore the need for increased awareness and the inclusion of gastrointestinal endoscopy as part of the diagnostic approach for this rare but potentially life-threatening condition.
A hotspot of diversity: novel Shewanella species isolated from Baltic Sea sediments delineate a sympatric species complex
Authors: Martín-Rodríguez Alberto J. , Fernández-Juárez Víctor , Valeriano Valerie D. , Mihindukulasooriya Indiwari , Ceresnova Livia , Joffré Enrique , Jensie-Markopoulos Susanne , Moore Edward R. B. , Sjöling Åsa
Published: August 2024

Two bacterial strains, SP1S1-4T and SP2S1-2T, were isolated from sediment samples collected in the Stockholm archipelago in November 2021. Following whole-genome sequencing, these strains were identified as tentatively belonging to two novel Shewanella genospecies, based on digital DNA–DNA hybridization, as implemented in the Type Strain Genome Server. Shewanella septentrionalis, Shewanella baltica and Shewanella hafniensis were, in this order and within a narrow genomic relatedness range, their closest genotypic relatives. Additional sampling and sequencing efforts led to the retrieval of distinct isolates that were monophyletic with SP1S1-4T and SP2S1-2T, respectively, based on phylogenomic analysis of whole-genome sequences. Comparative analyses of genome sequence data, which included blast-based average nucleotide identity, core genome-based and core proteome-based phylogenomics, in addition to MALDI-TOF MS-based protein profiling, confirmed the distinctness of the putative novel genospecies with respect to their closest genotypic relatives. A comprehensive phenotypic characterisation of SP1S1-4T and SP2S1-2T revealed only minor differences with respect to the type strains of S. septentrionalis, S. baltica and S. hafniensis. Based on the collective phylogenomic, proteomic, and phenotypic evidence presented here, we describe two novel genospecies within the genus Shewanella, for which the names Shewanella scandinavica sp. nov. and Shewanella vaxholmensis sp. nov. are proposed. The type strains are, respectively, SP2S1-2T (=CCUG 76457T=CECT 30688T), with a draft genome sequence of 5 041 805 bp and a G+C content of 46.3 mol%, and SP1S1-4T (=CCUG 76453T=CECT 30684T), with a draft genome sequence of 4 920147 bp and a G+C content of 46.0 mol%. Our findings suggest the existence of a species complex formed by the species S. baltica, S. septentrionalis, S. scandinavica sp. nov., and S. vaxholmensis sp. nov., with S. hafniensis falling in the periphery, where distinct genomic species clusters could be identified. However, this does not exclude the possibility of a continuum of genomic diversity within this sedimental ecosystem, as discussed herein with additional sequenced isolates.
The bioavailability of compounded and generic rapamycin in normative aging individuals: A retrospective study and review with clinical implications
Authors: Harinath Girish , Lee Virginia , Nyquist Andy , Moel Mauricio , Wouters Maartje , Hagemeier Jesper , Verkennes Brandon , Tacubao Colleen , Kauppi Krister , Morgan Stefanie L. , Isman Anar , Zalzala Sajad
Published: August 2024

Rapamycin, also known as sirolimus, has demonstrated great potential for application in longevity medicine. However, the bioavailability of generic and compounded rapamycin at longevity doses in normative aging individuals remains unknown. We conducted a retrospective, real-world study determining the 24-hour blood rapamycin levels to establish the relative bioavailability, dose-to-blood level linearity and inter-individual heterogeneity in a normative aging cohort. Participants received either compounded rapamycin (n = 23, dosages 5, 10, or 15 mg) or generic rapamycin (n= 44, dosages 2, 3, 6, or 8 mg) once per week, and were asked to obtain a sirolimus level blood draw 24 hours after dose self-administration. Similar blood rapamycin levels and a linear dose-to-blood level relationship were observed for both formulations, although a higher bioavailability per milligram of rapamycin was noted for the generic formulation (compounded averaged 0.287 (28.7%) bioavailability relative to generic rapamycin in (ng/mL) / mg rapamycin). While substantial inter-individual heterogeneity in blood rapamycin levels was observed for both formulations, repeat tests for individuals demonstrated high test-retest reliability. As we detected no significant association between bioavailability and measures of body mass index (BMI), sex, age, or length of time taking rapamycin, we suggest that individualized dosing and routine monitoring of blood rapamycin levels should be applied to ensure optimal longevity efficacy. Finally, we contextualize our data with a brief review of the literature on the currently available knowledge of rapamycin’s bioavailability in normative aging populations, and provide implications for the clinical use of rapamycin in longevity medicine moving forward.
Comparison of four intensive care scores in prediction of outcome after Veno-Arterial ECMO: A single center retrospective study
Authors: Sudarsanan Suraj , Sivadasan Praveen , Chandra Prem , Omar Amr S , Atuel Kathy Lynn Gaviola , Lone Hafeez Ulla , Ragab Hany O , Ehsan Irshad , Carr Cornelia S , Pattath Abdulrasheed , Al khulaifi Abdulaziz , Shouman Yasser Mahfouz Eltokhy , Al Mulla A/Wahid Mahmoud A.A.
Published: August 2024

Background

Assess the ability of APACHE II (acute physiology and chronic health evaluation II), SOFA (sequential organ failure assessment scores), Cardiac Surgery Score (CASUS) and SAVE (Survival after VA-ECMO) to predict outcomes in a cohort of patients undergoing Veno-Arterial ECMO (VA-ECMO).

Methods

Observational retrospective study of all patients admitted to Cardiothoracic Intensive Care Unit (CTICU) for a minimum duration of 24 hours after undergoing VA-ECMO insertion between years 2015 to 2022. Scores for APACHE II, SOFA and CASUS were calculated at 24 after ICU admission. SAVE score was calculated from the last available patient details within 24 hours of ECMO insertion. Demographic, clinical, and laboratory data relevant for the study was retrieved from electronic patient records.

Results

Pre-ECMO serum levels of lactates and creatinine were significantly associated with mortality. Lower ECMO flow rates at 4 hours and 12 hours after ECMO cannulation was significantly associated with survival to discharge. Development of arrythmias, acute kidney injury (AKI) and need of continuous renal replacement therapy (CRRT) while on ECMO were significantly associated with mortality. The APACHE-II, SOFA and CASUS, calculated at 24 hours of ICU admission were significantly higher amongst non-survivors. Following categorization of risk scores using ROC curve analysis, it was found that APACHE-II, SOFA and CASUS calculated at 24 hours of ICU admission after ECMO insertion demonstrated moderate predictive ability for mortality whereas SAVE score failed to predict mortality. APACHE-II >27 (AUC of 0.66) calculated at 24 hours of ICU admission after ECMO insertion, demonstrated the greatest predictive ability, for mortality. Multivariate logistic regression analysis of the four scores showed that APACHE-II > 27 and SOFA > 14 calculated at 24 hours of ICU admission after ECMO insertion, were independently significantly predictive of mortality.

Conclusions

The APACHE-II, SOFA and CASUS, calculated at 24 hours of ICU admission were significantly higher amongst non-survivors as compared to survivors. APACHE-II demonstrated the best mortality predictive ability. APACHE-II scores of 27 or above, and SOFA of 14 or above at 24 hours of ICU admission after ECMO cannulation can predict mortality and will aid physicians in decision making.
A hollow fiber membrane-based liver organoid-on-a-chip model for examining drug metabolism and transport
Authors: Myszczyszyn Adam , Münch Anna , Lehmann Vivian , Sinnige Theo , van Steenbeek Frank G. , Bouwmeester Manon , Samsom Roos-Anne , Keuper-Navis Marit , van der Made Thomas K. , Kogan Daniel , Braem Sarah , van der Laan Luc J. W. , Amirabadi Hossein Eslami , van de Steeg Evita , Masereeuw Rosalinde , Spee Bart
Published: August 2024

Liver-on-a-chip models predictive for both metabolism as well as canalicular and blood transport of drug candidates in humans are lacking. Here, we established an advanced, bioengineered and animal component-free hepatocyte-like millifluidic system based on 3D hollow fiber membranes (HFMs), recombinant human laminin 332 coating and adult human stem cell-derived organoids. Organoid fragments formed polarized and tight monolayers on HFMs with improved hepatocyte-like maturation, as compared to standard 3D organoid cultures in Matrigel from matched donors. Gene expression profiling and immunofluorescence revealed that hepatocyte-like monolayers expressed a broad panel of phase I (e.g., CYP3A4, CYP2D6) and II (UGTs, SULTs) drug-metabolizing enzymes and drug transporters (e.g., OATP1B3, MDR1 and MRP3). Moreover, statically cultured monolayers displayed phase I and II metabolism of a cocktail of six relevant compounds, including midazolam and 7-hydroxycoumarin. We also demonstrated the disposition of midazolam in the basal/blood-like circulation and apical/canalicular-like compartment of the millifluidic chip. Finally, we connected the system to the other two PK/ADME-most relevant organ systems,i.e.small intestine- and kidney proximal tubule-like to study the bioavailability of midazolam and coumarin, and excretion of metformin. In conclusion, we generated a proof-of-concept liver organoid-on-a-chip model for examining metabolism and transport of drugs, which can be further developed to predict PK/ADME profiles in humans.
The role of mitochondrial complex I in the proinflammatory response to polylactide implants
Authors: Maduka Chima V. , Makela Ashley V. , Tundo Anthony , Ural Evran , Stivers Katlin B. , Alhaj Mohammed , Narayan Ramani , Goodman Stuart B. , Ashammakhi Nureddin , Elisseeff Jennifer H. , Hankenson Kurt D. , Contag Christopher H.
Published: August 2024

During the foreign body response, immune cells are metabolically rewired after exposure to breakdown products of various biomaterials, including polylactide (PLA) and polyethylene. Particles of polyethylene interact with Toll-like receptor 4 on macrophages, resulting in increased oxygen consumption that forms reactive oxygen species at complex I of the mitochondrial electron transport chain (mETC). However, PLA degradation products bind to monocarboxylate transporters for downstream signaling with elevated oxygen consumption rates, whose functional implication is unclear and remains inferred from cellular responses to polyethylene biomaterials. By chemically probing the function of the mETC, we show that proinflammatory macrophages activated by exposure to amorphous PLA (aPLA) breakdown products rely on mitochondrial respiration for ATP production, independent of oxygen consumption rates. In contrast, macrophages activated by semi-crystalline PLA (cPLA) breakdown products exhibit a metabolic phenotype wherein ATP levels are unaffected by changing oxygen consumption rates. In subcutaneous implants, the incorporation of metformin in aPLA or cPLA to chemically inhibit complex I did not effectively modulate the proinflammatory response to biomaterials, suggesting that PLA degradation products elicit a distinct metabolic program, thus providing an alternative perspective on the role of mitochondrial respiration in the inflammatory response to biomaterials.
Evolution of mental traits linked to cultural development in modern humans and Neanderthals
Authors: Moriya Yuka , Fujito Naoko T , Terahara Masahiro , Takahata Naoyuki , Satta Yoko , Teshima Kosuke M , Hayakawa Toshiyuki
Published: August 2024

A cumulative process of cultural evolution occurred globally alongside the spread of anatomically modern humans (AMHs). This process of evolution was likely accompanied by global changes in mental and behavioral phenotypes, resulting in cultural differences between AMHs and Neanderthals. Globally, selective increases of frequencies were detected in alleles, which contributed to the suppression of neuroticism and advanced learning. This finding indicates that neuroticism was suppressed and learning behaviors developed through the global spread of AMHs. It suggests that global adaptation to psychosocial stress occurred, which contributed to cumulative cultural evolution by increasing cooperative learning. A comparison of phenotypic trends at the population level indicates that such globally occurring adaptive evolution, entailing neuroticism suppression and increased learning behaviors has been more significant in AMHs than in Neanderthals. However, adaptive evolution toward greater intelligence was more significant in Neanderthals than in AMHs. These findings suggest that mental traits involved in cultural development evolved differently in AMHs and Neanderthals, and that learning behaviors such as cooperative learning, rather than intelligence, played an important role in AMH evolution.
A compact prism-based microscope for high sensitive measurements in fluid biopsy
Authors: Perego Laura , Dallari Caterina , Falciani Chiara , Pini Alessandro , Gardini Lucia , Credi Caterina , Pavone Francesco Saverio
Published: August 2024

The increasing demand for sensitive, portable, and cost-effective disease detection methods has raised significant interest in the development of biosensors for rapid and early-stage diagnosis, population mass-screening, and bedside monitoring. Although a certain number of sensing devices with high sensitivity has experienced considerable progress, their practical application has been hindered by challenges in replicating instrumental systems, obtaining rapid and multiplexed signals, and the high cost of manufacturing. In response, we present a streamlined prism-based Total Internal Reflection system which, in combination with surface functionalization techniques on gold nanoparticles, is capable of facilitating Evanescent Wave scattering for the highly sensitive and rapid detection of specific analytes in synthetic liquids and real human samples. The system achieves a remarkable limit of detection of 1 fg/mL concentration for the targeted pathological biomarker. Our innovative design addresses the limitations of existing technologies by reducing costs, minimising overall size, and ensuring swift biofluid analysis with remarkable sensitivity. To validate its efficacy, we conducted scattering experiments in synthetic and human serum samples, exploiting functionalized AuNPs to recognize bacterial lipopolysaccharides as biomarkers for sepsis disease. The cohesive integration of these techniques hopefully makes this biosensing setup a promising candidate for potential clinical deployment, meeting the pressing requirements for rapid personalised diagnosis, large-scale population screening and bed-monitoring.
Mesenchymal Meis2 controls whisker development independently from trigeminal sensory innervation
Authors: Kaplan Mehmet Mahsum , Hudacova Erika , Matejcek Miroslav , Tuaima Haneen , Krivanek Jan , Machon Ondrej
Published: August 2024

Hair follicle development is initiated by reciprocal molecular interactions between the placode-forming epithelium and the underlying mesenchyme. Cell fate transformation in dermal fibroblasts generates a cell niche for placode induction by activation of signaling pathways WNT, EDA, and FGF in the epithelium. These successive paracrine epithelial signals initiate dermal condensation in the underlying mesenchyme. Although epithelial signaling from the placode to mesenchyme is better described, little is known about primary mesenchymal signals resulting in placode induction. Here we show thatMeis2expression in cells derived from the neural crest is critical for whisker formation, and also for branching of trigeminal nerves. While whisker formation is independent of the trigeminal sensory innervation, MEIS2 in mesenchymal dermal cells orchestrates the initial steps of epithelial placode formation and subsequent dermal condensation. MEIS2 regulates the expression of transcription factorFoxd1, which is typical of pre-dermal condensation. However, deletion ofFoxd1does not affect whisker development. Overall, our data suggest an early role of mesenchymal MEIS2 during whisker formation and provide evidence that whiskers can normally develop in the absence of sensory innervation orFoxd1expression.
Comparison of indicators for assessing wasting among children younger than 5 years: a longitudinal study in northern Kenya
Authors: Wilunda Calistus , Thuita Faith , Mwangi Bonventure , Flax Valerie L. , Lutter Chessa K. , Adair Linda , Amugsi Dickson , Odhiambo Hazel , Anono Esther , Webale Albert , Chepkwony Gillian , Ekiru Stephen , Kimani-Murage Elizabeth , Sidze Estelle
Published: August 2024

Mid-upper arm circumference (MUAC) or weight-for-height/length Z-score (WHZ) are recommended in wasting diagnosis, but there are discrepancies between these indicators in identifying children as wasted. We compared the extent to which WHZ, MUAC, MUAC-for-age Z-score (MAZ) identify the same children as wasted and assessed the predictors of discordance and concordance in wasting diagnosis by these indicators using data from a longitudinal study of children younger than 3 years at recruitment in Turkana and Samburu counties. Wasting prevalence was consistently lower based on MUAC than WHZ and MAZ. Compared to WHZ, MAZ had higher sensitivity than MUAC, with the sensitivity of MAZ increasing and MUAC decreasing with age. Both indicators had high specificity. WHZ had a better agreement with MAZ than MUAC in wasting diagnosis. Older children were less likely to be classified as wasted by MUAC alone or by both MUAC and WHZ but were more likely to be classified as wasted by WHZ alone, MAZ alone or by both MAZ and WHZ. Compared to girls, boys were less likely to be classified as wasted by MUAC alone but more likely to be classified as wasted by WHZ alone. Stunted children were more likely to be classified as wasted by MUAC alone, MAZ alone, both MUAC and WHZ, and both MAZ and WHZ but not by WHZ alone. Classifications of wasting based on WHZ, MAZ, and MUAC are age, sex, and stunting status dependent. Compared to WHZ, MAZ is a more reliable and valid indicator than MUAC in these settings.
Cross-Cultural Adaptation of the Physician Orders for Life-Sustaining Treatment Form in Greece; a pilot cross-sectional descriptive study
Authors: Moustakas Dimitrios C. , Bani Alexia , Ntalaouti Eleni , Vechlidis Nikolaos , Charalampidis Charalampos , Chalvatzis Stamatios , Grigoropoulou Sotiria , Faltsetas Stylianos , Boumpas Dimitrios T. , Kravvariti Evrydiki , Trokanas Theodoros , Vayena Effy , Tsiodras Sotirios
Published: August 2024

The current legal framework in Greece does not permit withholding medical interventions to allow natural death, leading to a lack of documented advance directives to guide clinical practice. The aim of this pilot descriptive study is to culturally adapt the Physician Orders for Life-Sustaining Treatment (POLST) form, and use it as a framework with which to assess the readiness of Greek residents for discussions on medical care near the end of life. Patients with severely limited prognosis and/or their family members were interviewed by attending physicians who then recorded their wish with regards to Do-Not-Resuscitate (DNR) status on the adapted POLST form, as well as their level of agreement with signing a similar form. Thirty-one patients with an age range of 18 to 109 years old participated. All had severe prognosis due to various end-stage diseases. Sixteen patients (51.6%) wished for DNR status and didn’t wish for further intervention in case they suffered cardio-respiratory arrest. Presence of an end-stage malignancy was associated with a higher chance of DNR preference (OR: 8.8, 95%CI 1.5-50, p = 0.017) or comfort measures only (OR: 5.6, 95%CI 1.1-30, p = 0.05). This pilot study of patients with severe prognosis hospitalized in a tertiary care center in Greece showed preliminary evidence of high acceptance of natural death and DNR status. POLST forms could be used as a framework for advance care planning through shared decision-making, thus reducing unwarranted treatments and enhancing trust between healthcare professionals and patients at the end of life.
Brain transcriptomic signatures for mood disorders and suicide phenotypes: an anterior insula and subgenual ACC network postmortem study
Authors: Arasappan Dhivya , Spears Abigail , Shah Simran , Mayfield Roy D , Akula Nirmala , McMahon Francis J. , Jabbi Mbemba
Published: August 2024

Mood disorders affect over ten percent of humans, but studies dissecting the brain anatomical and molecular neurobiological mechanisms underlying mood (dys)functions have not consistently identified the patterns of pathological changes in relevant brain regions. Recent studies have identified pathological changes in the anterior insula (Ant-Ins) and subgenual anterior cingulate (sgACC) brain network in mood disorders, in line with this network’s role in regulating mood/affective feeling states. Here, we applied whole-tissue RNA-sequencing measures of differentially expressed genes (DEGs) in mood disorders versus (vs.) psychiatrically unaffected controls (controls) to identify postmortem molecular pathological markers for mood disorder phenotypes. Using data-driven factor analysis of the postmortem phenotypic variables to determine relevant sources of population variances, we identified DEGs associated with mood disorder-related diagnostic phenotypes by combining gene co-expression, differential gene expression, and pathway-enrichment analyses. We found downregulation/under expression of inflammatory, and protein synthesis-related genes associated with psychiatric morbidity (i.e., all co-occurring mental disorders and suicide outcomes/death by suicide) in Ant-Ins, in contrasts to upregulation of synaptic membrane and ion channel-related genes with increasedpsychiatric morbidityin sgACC. Our results identified a preponderance of downregulated metabolic, protein synthesis, inflammatory, and synaptic membrane DEGs associated withsuicideoutcomes in relation to a factor representinglongevityin the Ant-Ins and sgACC (AIAC) network. Our study revealed a critical brain network molecular repertoire for mood disorder phenotypes, including suicide outcomes and longevity, and provides a framework for defining dosage-sensitive (i.e., downregulated vs. upregulated) molecular signatures for mood disorder phenotypic complexity and pathological outcomes.