bluuebunny/crossref_metadata_2025 huggingface dataset:
SMN depletion impairs skeletal muscle formation and maturation in a mouse model of SMA
Authors: Liu Hong , Chehade Lucia , Deguise Marc-Olivier , De Repentigny Yves , Kothary Rashmi
Published: November 2024

Spinal muscular atrophy (SMA) is characterized by low levels of the ubiquitously expressed Survival Motor Neuron (SMN) protein, leading to progressive muscle weakness and atrophy. Skeletal muscle satellite cells play a crucial role in muscle fiber maintenance, repair, and remodelling. While the effects of SMN depletion in muscle are well documented, its precise role in satellite cell function remains largely unclear. Using the Smn2B/− mouse model, we investigated SMN-depleted satellite cell biology through single fiber culture studies. Myofibers from Smn2B/− mice were smaller in size, shorter in length, had reduced myonuclear domain size, and reduced sub-synaptic myonuclear clusters—all suggesting impaired muscle function and integrity. These changes were accompanied by a reduction in the number of myonuclei in myofibers from Smn2B/− mice across all disease stages examined. Although the number of satellite cells in myofibers was significantly reduced, those remaining retained their capacity for myogenic activation and proliferation. These findings support the idea that a dysregulated myogenic process could be occurring as early in muscle stem cells during muscle formation and maturation in SMA. Targeting those pathways could offer additional options for combinatorial therapies for SMA.
Quantifying uncertainty in the contribution of mesopelagic fishes to the biological carbon pump in the Northeast Atlantic Ocean
Authors: McMonagle Helena , Llopiz Joel K , Maas Amy E , Steinberg Deborah K , Govindarajan Annette F , Essington Timothy E
Published: November 2024

Mesopelagic fishes may contribute substantially to marine carbon export and sequestration. However, uncertainty in this contribution due to limited precision of mesopelagic biomass and bioenergetic rate estimates has not been thoroughly quantified for any study site. Datasets that can confront these challenges are rare, particularly for comparing fish-mediated carbon flux to other biological carbon pump pathways. Using data from a unique three-ship expedition in spring 2021 in the subarctic Northeast Atlantic Ocean, we compare carbon transported by adult fish, zooplankton, and sinking particles, and calculate uncertainty in the relative contribution of fishes. Results indicate biomass- and bioenergetic-based uncertainty contributed roughly equally to variance in estimated carbon transport. The plausible range of mesopelagic fish carbon flux spans an order of magnitude: 1.6–21 mg C m−2 d−1 to 200 m depth and 0.52–9.6 mg C m−2 d−1 to 500 m. Fishes contributed ∼0.52%–18% at 200 m to the total biological carbon pump, and ∼0.43%–13% at 500 m. Of the fish-mediated carbon transport to 200 m, ∼8%–30% is sequestered on climate-relevant time scales (>100 years). This reinforces that carbon transport should not be conflated with carbon sequestration. These findings have implications for prioritizing future empirical measurements, evaluating trade-offs in fisheries management, and understanding the role of fishes in the biological carbon pump.
Conspicuous parasite modifies appearance and energetics of a marine copepod
Authors: Eliassen Lasse Krøger , Garvang Even Sletteng , Andersen Tom , Engseth Erik , Kristiansen Kåre Andre , Wiik-Nielsen Jannicke , Titelman Josefin
Published: November 2024

Parasitism is an important driver of ecosystem processes. Copepods are fundamental trophic links in marine food webs and harbour many microeukaryotic parasites, but unreliable access to infected individuals limits quantitative studies of parasite infection costs. Calanus spp., (helgolandicus or finmarchicus), infected with the Yellow-Hyphal Parasite become pigmented and are found near the surface, suggesting predator-mediated dispersal. Conventional markers prevented phylogenetic inference but confirmed that the parasite is not Ichthyophonus hoferi, as previously thought. We identified the pigments, quantified the pigment content and respiration rate, and derived stable isotope signatures of infected and uninfected Calanus spp. to examine costs of infection. We found that the pigments were astaxanthin and β-carotene, associated with the host and parasite, respectively. Parasitized hosts had increased astaxanthin content, reduced respiration rate, and lower lipid content. Ultrastructure imaging revealed parasitic cells associated with lipids in the haemocoel. The changes to host phenotype have detrimental impacts on energetics and the ecology of Calanus. We discuss the role of pigments in parasite-host interactions and suggest that the parasite produces β-carotene pigment for its physiological benefits. The trade-off between physiological benefits of pigments and conspicuousness for parasites is relevant in zooplankton-host systems, as zooplankton rely heavily on transparency for survival.
Early Viral Dynamics Predict Human Immunodeficiency Virus Posttreatment Control After Analytic Treatment Interruption
Authors: Magombedze Gesham , Vendrame Elena , SenGupta Devi , Geleziunas Romas , Little Susan , Smith Davey , Walker Bruce , Routy Jean-Pierre , Hecht Frederick M , Chun Tae-Wook , Sneller Michael , Li Jonathan Z , Deeks Steven G , Peluso Michael J
Published: November 2024

Background

A key research priority for developing a human immunodeficiency virus (HIV) cure strategy is to define the viral dynamics and biomarkers associated with sustained posttreatment control. The ability to predict the likelihood of sustained posttreatment control or noncontrol could minimize the time off antiretroviral therapy (ART) for those destined to be controllers and anticipate longer periods off ART for those destined to be controllers.

Methods

Mathematical modeling and machine learning were used to characterize virologic predictors of long-term virologic control, using viral kinetics data from several studies in which participants interrupted ART. Predictors of post-ART outcomes were characterized using data accumulated from the time of treatment interruption, replicating real-time data collection in a clinical study, and classifying outcomes as either posttreatment control (plasma viremia, ≤400 copies/mL at 2 of 3 time points for ≥24 weeks) or noncontrol.

Results

Potential predictors of virologic control were the time to rebound, the rate of initial rebound, and the peak plasma viremia. We found that people destined to be noncontrollers could be identified within 3 weeks of rebound (prediction scores: accuracy, 80%; sensitivity, 82%; specificity, 71%).

Conclusions

Given the widespread use of analytic treatment interruption in cure-related trials, these predictors may be useful to increase the safety of analytic treatment interruption through early identification of people who are unlikely to become posttreatment controllers.
Diagnostic uncertainties in patients with bacteraemia: impact on antibiotic prescriptions and outcome
Authors: Roger Pierre-Marie , Strzelecki Anne-Claire , Dautezac Véronique , Hennet Marc-Antoine , Borredon Gaëlle , Brisou Patrick , Girard Delphine , Assi Assi
Published: November 2024

Objectives

To establish a formal diagnosis in infectious disease is not an easy task. Our aim was to characterize diagnostic uncertainty (DU) in patients for whom blood cultures were positive (PBC) and to determine its impact on both the antibiotic therapy and the outcome.

Methods

This was a prospective multicentre study including PBC for 6 months. The laboratory gave the PBC result to the infectious disease (ID) specialists in real time (24/7). The latter analysed all data from electronic patient charts and gave therapeutic advice to the physicians in charge of the patient to either initiate an antibiotic therapy, or to modify or to pursue continuing antimicrobial treatment. A DU was defined as no diagnosis of ID after thorough reading of the patient’s chart, or more than two diagnoses despite two medical opinions obtained before PBC. An unfavourable outcome was defined by the occurrence of death during hospitalization.

Results

One hundred and nighty-nine PBCs were communicated to ID specialists, including 93 DUs (47%). In multivariate analysis, DU was associated with hospitalization in medical wards: [adjusted odds ratio (AOR) (95% CI): 6.94 (3.41–14.28)], the advice to initiate an antibiotic treatment: [3.89 (1.56–9.70)] and piperacillin-tazobactam use [3.75 (1.56–9.00)]; ICU requirement at initiation of care was a protective factor [0.38 (0.17–0.84)]. An unfavourable outcome was observed in 22 cases, and in a second logistic regression showed that DU was associated with the latter [AOR (95% CI): 5.07 (1.60–16.12)].

Conclusion

DUs were frequent during infections proved by PBC, and were associated with admission in medical wards, broad-spectrum antibiotic use and a high rate of unfavourable outcomes.
Development of a PCR assay for rapid and accurate detection of an emerging vanB Enterococcus faecium clone in the Capital Region of Denmark
Authors: Knudsen Maja Johanne Søndergaard , Barker Jensen Christel , Jørgensen Rikke Lind , Petersen Andreas Munk , Qvist Kristiansen Gitte , Lisby Jan Gorm , Worning Peder , Westh Henrik , Pinholt Mette
Published: November 2024

Objectives

To develop and validate a real-time PCR assay detecting the sequence bridging Tn1549 and the Enterococcus faecium chromosome in the emerging vanB vancomycin-resistant E. faecium (VREfm) clone (ST80/CT2406).

Methods

The Tn1549 insertion site was determined on routinely sequenced VREfm isolates. The outer boundaries of Tn1549 and adjoining host bacterial sequences were determined using a BLAST search in the silent information regulator gene sir2. Next, the primers and probe were developed, targeting the sequence bridging Tn1549 and the E. faecium chromosome. Finally, the PCR assay was validated on well-characterized strains and prospectively performed on rectal screening samples submitted to our laboratory.

Results and conclusions

The PCR assay proved to be accurate and provide rapid diagnosis of the emerging vanB VREfm in rectal screening samples.
International organizations’ practice in the interpretation of their constituent instruments
Authors: Pan Kaijun
Published: November 2024

Subsequent practice of international organizations plays an important role in the interpretation of their constituent instruments. Based on Articles 5 and 31(3) of the Vienna Convention on the Law of Treaties (VCLT), when such practices have become established or have been consented to by all States parties, they can be considered authoritative interpretations. The legal basis for considering practices of international organizations in other circumstances, however, is not entirely clear. The International Law Commission proposed that these practices may still be considered in the application of Articles 31 and 32 of the VCLT but left many issues undiscussed. This article argues that it is possible to consider international organizations’ practice in the application of Article 31 if a strong inference about the original intention of States parties can be drawn therefrom. To address difficulties involved in evaluating the probative value of international organizations’ practice, this article borrows a tool from probability theory—likelihood ratio—and shows that, absent a major change of circumstances, international organizations’ earlier practice can be seen as credible evidence of States parties’ original intention and considered in the application of Article 31.
A new method for AFM mechanical characterization of heterogeneous samples with finite thickness
Authors: Kontomaris Stylianos-Vasileios , Malamou Anna , Stylianou Andreas
Published: November 2024

Accurate mathematical expressions have previously been derived for determining the Young's modulus of thin homogeneous samples on rigid substrates when tested using atomic force microscopy. These equations have generally been applied to determine the mechanical properties (in terms of Young's modulus) of thin biological samples bonded to rigid substrates, such as cells. However, biological materials are highly heterogeneous at the nanoscale, so their mechanical properties vary significantly with indentation depth. Consequently, a crucial question is whether these equations are mathematically valid in such cases and if they can lead to reproducible results. In this paper, a rigorous mathematical analysis is used to investigate the validity of equations derived for homogeneous samples with finite thickness when applied to heterogeneous thin samples on rigid substrates. Using the aforementioned analysis, the classical equations are modified to account for depth-dependent mechanical properties. Consequently, the depth-dependent mechanical properties of heterogeneous samples with finite thickness are characterized using appropriate functions instead of single Young's modulus values. Force–indentation data from human fibroblasts and murine breast cancer cells are processed using the method presented in this paper, resulting in accurate and reproducible results.
Insomnia severity and obesity mediated by health behaviors in adolescents
Authors: Triplett Olivia M , Morrell Holly E R , Van Dyk Tori R
Published: November 2024

Objective

Sleep difficulties in youth have been associated with numerous negative outcomes, such as higher risk of obesity. Though the relationship between sleep and obesity is not well clarified, past research has shown that modifiable health behaviors, such as diet, physical activity, and screen time, may explain this relationship. The purpose of this study was to simultaneously examine these health behaviors as mediators of the relationship between insomnia severity and obesity among a sample of adolescents aged 12–18 years.

Method

English-speaking parents/legal guardians of adolescents were invited to participate in an online survey focused on pediatric sleep patterns, health behaviors, and weight. Parents/guardians (N = 599) reported on their adolescent’s diet (i.e., consumption of fruits/vegetables, fast food, and breakfast), physical activity, screen time, and BMI. A multiple mediation analysis was run to test these health behaviors as mediators of the relationship between insomnia severity and BMI, after controlling for sex, age, race, and poverty.

Results

While insomnia was related to most health behaviors, screen time was the only significant mediator of the relationship between insomnia and BMI, after controlling for the effects of the other mediators and all covariates, ab = .04, 95% CrI [.01, .09].

Conclusions

Screen time has implications for both adolescents’ sleep health and weight. Pediatric clinicians should systematically assess for, and provide, recommendations on ways to improve sleep and screen time use, in addition to providing traditional dietary and physical activity recommendations.
Timing of puberty suppression in transgender adolescents and sexual functioning after vaginoplasty
Authors: van der Meulen Isabelle S , Bungener Sara L , van der Miesen Anna I R , Hannema Sabine E , Kreukels Baudewijntje P C , Steensma Thomas D , Bouman Mark-Bram , de Vries Annelou L C
Published: November 2024

Background

Sexual function in transgender adolescents after puberty suppression has been a topic of recent clinical and scientific questions.

Aim

This study aimed to explore the long-term effects of early treatment with puberty suppression on sexual functioning of transfeminine individuals after vaginoplasty.

Methods

This retrospective cohort study included 37 transfeminine individuals treated with a gonadotropin-releasing hormone agonist (puberty suppression), estrogen, and vaginoplasty (penile inversion technique or intestinal vaginoplasty) at the Center of Expertise on Gender Dysphoria in Amsterdam, the Netherlands, between 2000 and 2016.

Outcomes

Experiences regarding sexual functioning and difficulties were assessed with a self-developed questionnaire ~1.5 years after genital gender-affirming surgery and compared between early (Tanner stage G2-3) and late (Tanner stage G4-5) treatment with puberty suppression.

Results

Following surgery, 91% of transfeminine individuals was able to experience sexual desire, 86% experienced arousal, and 78% could attain an orgasm. Seventy-five percent of transfeminine individuals who had not experienced an orgasm pre-surgery were able to experience one post-surgery. Of all participants, 62% reported having tried penile-vaginal intercourse post-surgery. The majority reported the presence of one or multiple sexual challenges. There were no significant differences in postoperative sexual function or sexual difficulties between groups treated with early versus late puberty suppression.

Clinical Implications

With these findings, more adequate and tailored information on the expected effects of early endocrine gender-affirming treatment (including puberty suppression) can be given by healthcare professionals.

Strengths and Limitations

This is the first study that has assessed sexual functioning of transgender individuals treated with puberty suppression, and has differentiated between the pubertal stage at treatment initiation. Limitations were the small cohort size and retrospective study design. This study focuses on sexual functioning, however, it is important to realize sexual wellbeing is multifactorial and encompasses more than genital functioning or the ability to have certain sexual experiences.

Conclusion

This study found that post-vaginoplasty transfeminine individuals after both early and late suppression of puberty have the ability to experience sexual desire and arousal, and to achieve orgasms. Outcomes are comparable to previous findings in those who started treatment in adulthood.
Chronic Leg Ischemia Caused by Arterial Bullet Embolization
Authors: Demirkiran Tuna , Özdem Tayfun , Akyol Furkan Burak , Erol Gökhan , Karabacak Kubilay
Published: November 2024

Intravascular shrapnel or bullet embolization after a gunshot injury is rare, with fewer than 200 cases reported over the past century. Military injuries typically have high energy transfer, making this phenomenon less prevalent. A 22-year-old military personnel presented with chronic leg ischemia resulting from arterial bullet embolization. Before 4 months, he had sustained a military injury and subsequently required hospitalization for pneumohemothorax. A 21-mm bullet obstructing the popliteal artery caused chronic leg ischemia and was scheduled for elective vascular surgery. Physicians should be aware of potential bullet embolization indications in gunshot wound patients to prevent complications, ensuring early detection and appropriate treatment for successful management.
Magnetic field evolution of hot exoplanets
Authors: Kilmetis K , Vidotto A A , Allan A , Kubyshkina D
Published: November 2024

Numerical simulations have shown that the strength of planetary magnetic fields depends on the convective energy flux emerging from planetary interiors. Here, we model the interior structure of gas giant planets using mesa, to determine the convective energy flux that can drive the generation of magnetic field. This flux is then incorporated in the Christensen et al. dynamo formalism to estimate the maximum dipolar magnetic field $B^\mathrm{(max)}_\mathrm{dip}$ of our simulated planets. First, we explore how the surface field of intensely irradiated hot Jupiters ($\sim 300\,\mathrm{ M}_{\oplus }$) and hot Neptunes ($\sim 20\,\mathrm{ M}_{\oplus }$) evolve as they age. Assuming an orbital separation of 0.1 au, for the hot Jupiters, we find that $B^\mathrm{(max)}_\mathrm{dip}$ evolves from 240 G at 500 Myr to 120 G at 5 Gyr. For hot Neptunes, the magnetic field evolves from 11 G at young ages and dies out at $\gtrsim$ 2 Gyr. Furthermore, we also investigate the effects of atmospheric mass fraction, atmospheric evaporation, orbital separations $\alpha$, and additional planetary masses on the derived $B^\mathrm{(max)}_\mathrm{dip}$. We found that $B^\mathrm{(max)}_\mathrm{dip}$ increases with $\alpha$ for very close-in planets and plateaus out after that. Higher atmospheric mass fractions lead in general to stronger surface fields, because they allow for more extensive dynamo regions and stronger convection.
Systematic deletion of symmetrical CFTR exons reveals new therapeutic targets for exon skipping antisense oligonucleotides
Authors: Pena-Rasgado Cecilia , Rodriguez-Manriquez Elvia , Dundr Miroslav , Bridges Robert J , Hastings Michelle L , Michaels Wren E
Published: November 2024

There is a major need for therapeutics that treat disease caused by premature termination codons (PTCs). Splice-switching antisense oligonucleotides (ASOs) can be directed to block splicing and cause exon skipping, a process that can be used to effectively remove PTCs from an mRNA. This ASO-induced exon skipping can restore protein coding potential when the exons on either side of the skipped exon are in the same reading frame, or symmetrical. We demonstrate the potential of this approach as a therapeutic using the cystic fibrosis (CF) transmembrane regulator (CFTR) gene, which has CF-associated, PTC-causing variants in all 27 of its exons. We functionally screened all CFTR isoforms that can be generated by deletion of symmetrical exons and identify four that are functionally responsive to CFTR modulators. We identified ASOs that induce skipping of these exons and show that they recover CFTR function in airway cells derived from individuals with CFTR PTC variants. This study demonstrates that systematic functional analysis of in-frame exon-deleted protein isoforms can successfully identify targets for ASO-based splice-switching therapies, a therapeutic concept that can be broadly applied to any multi-exon protein-coding gene disrupted by PTCs.
Radiological risk assessment of phosphate fertilizer application on farmlands in Ondo State, Nigeria
Authors: Ogunbiyi Olajide Kehinde , Ojuola Tolulope Ayodeji , Agbele Alaba Tolulope , Ogunlana Funmilola Olusola , Oludare Ojo Emmanuel , Alabi Abdul-Hafiz Abolade
Published: November 2024

This study assesses the radiological risks associated with phosphate fertilizer application on farmlands in Ondo State, Nigeria. Soil samples from ten agricultural towns were analyzed for radionuclide concentrations using gamma-ray spectrometry. Primordial radionuclides such as 238U, 232Th, and 40K were examined, with 40K showing the highest concentration due to the potassium-rich nature of phosphate fertilizers. Spatial variability in radionuclide concentrations was observed, attributed to agricultural activities. Despite variations, mean activity concentrations were below global averages, indicating low radiological risks. Hazard indices, radium equivalent concentrations, and absorbed dose rates were all within safe limits. The annual effective dose equivalent was significantly lower than recommended levels, and excess lifetime cancer risk estimates were below the global average. The study emphasizes the importance of educating farmers on the potential adverse effects of radionuclides and recommends reducing the use of inorganic fertilizers to promote eco-friendly agricultural practices.
A Representative Profile of MSW Graduates in the United States
Authors: Jensen Todd M , Zerden Lisa de Saxe , Lombardi Brianna M
Published: November 2024

As the United States faces burgeoning behavioral health needs and a growing recognition of the inextricable link between social conditions and health outcomes and quality-of-life indicators, a current representative profile of the MSW workforce with respect to sociodemographic and employment characteristics can provide a reference point for ongoing assessments of that workforce. The profile also can establish a baseline by which efforts to bolster the diversity and strength of the MSW workforce can be grounded. The core aim of the current study was to generate a nationally representative, descriptive profile of MSW graduates in the United States using a sample of 1,028 MSW graduates (representing a subpopulation of 691,061 individuals) from the 2021 National Survey of College Graduates. Weighted univariate and bivariate analyses were conducted to generate a descriptive profile of MSW graduates with respect to sociodemographic, education, and employment characteristics. Study findings can help employers, health services researchers, policymakers, and practitioners understand the context of the MSW workforce as it relates to diversity, labor workforce projection data, and student loan and salary considerations. This information can guide future policy and training goals to support the future vitality of the social work profession.
BioRxToolbox: a computational framework to streamline genetic circuit design in molecular data communications
Authors: Durmaz Merve Gorkem , Tulluk Neval , Aksoy Recep Deniz , Yilmaz Huseyin Birkan , Yang Bill , Wipat Anil , Pusane Ali Emre , Mısırlı Göksel , Tugcu Tuna
Published: November 2024

Developments in bioengineering and nanotechnology have ignited the research on biological and molecular communication systems. Despite potential benefits, engineering communication systems to carry data signals using biological messenger molecules and engineered cells is challenging. Diffusing molecules may fall behind their schedule to arrive at the receiver, interfering with symbols of subsequent time slots and distorting the signal. Existing theoretical molecular communication models often focus solely on the characteristics of a communication channel and fail to provide an end-to-end system response since they assume a simple thresholding process for a receiver cell and overlook how the receiver can detect the incoming distorted molecular signal. In this paper, we present a model-based and computational framework called BioRxToolbox for designing diffusion-based and end-to-end molecular communication systems coupled with synthetic genetic circuits. We describe a novel framework to encode information as a sequence of bits, each transmitted from the sender as a burst of molecules, control cellular behavior at the receiver, and minimize cellular signal interference by employing equalization techniques from communication theory. This approach allows the encoding and decoding of data bits efficiently using two different types of molecules that act as the data carrier and the antagonist to cancel out the heavy tail of the former. Here, BioRxToolbox is demonstrated using a biological design and computational simulations for various communication scenarios. This toolbox facilitates automating the choice of communication parameters and identifying the best communication scenarios that can produce efficient cellular signals.
LC3B-regulated autophagy mitigates zinc oxide nanoparticle-induced epithelial cell dysfunction and acute lung injury
Authors: Chen Ruonan , Luo Sen , Zhang Yunxiao , Mao Lejiao , Diao Jun , Cheng Shuqun , Zou Zhen , Chen Chengzhi , Qin Xia , Jiang Xuejun , Zhang Jun
Published: November 2024

Zinc oxide nanoparticles (ZnONPs) are widely utilized across various industries, raising concerns about their potential toxicity, especially in the respiratory system. This study explores the role of autophagy, regulated by microtubule-associated protein 1A/1B-light chain 3B (LC3B), in ZnONPs-induced toxicity using both in vivo (LC3B knockout mice) and in vitro (BEAS-2B cells) models. Our findings demonstrate that LC3B-regulated autophagy mitigates ZnONPs-induced epithelial cell dysfunction and acute lung injury. In the absence of LC3B, oxidative stress, inflammation, and intracellular zinc accumulation are exacerbated, resulting in mitochondrial dysfunction and epithelial cell death. In vitro, LC3B knockdown disrupted zinc ion transporter expression and impaired mitophagic flux in BEAS-2B cells. Treatment with zinc ion chelators alleviated these toxic effects, confirming that free zinc ions play a critical role in driving ZnONPs toxicity. These findings highlight that targeting autophagy and maintaining zinc homeostasis could offer therapeutic strategies to reduce ZnONPs-induced lung damage.
Impact of Knee Osteoarthritis and Arthroplasty on Full Body Sagittal Alignment in Adult Spinal Deformity Patients
Authors: Daher Mohammad , Daniels Alan H , Knebel Ashley , Balmaceno-Criss Mariah , Lafage Renaud , Lenke Lawrence G , Ames Chrisotpher P , Burton Douglas , Lewis Stephen M , Klineberg Eric O , Eastlack Robert K , Gupta Munish C. , Mundis Gregory M. , Gum Jeffrey L. , Hamilton Kojo D. , Hostin Richard , Passias Peter G. , Protopsaltis Themistocles S. , Kebaish Khaled M. , Kim Han Jo , Schwab Frank , Shaffrey Christopher I. , Smith Justin S. , Line Breton , Bess Shay , Lafage Virginie , Diebo Bassel G ,   on behalf of the International Spine Study Group (ISSG)
Published: November 2024

Study Design.

Retrospective analysis of prospectively collected data

Objective.

This study evaluates the impact of knee osteoarthritis (OA) and knee arthroplasty on alignments and patient-reported outcomes measures (PROMS) of patients undergoing adult spinal deformity (ASD) corrective surgery.

Background.

The relationship between knee OA and spinal alignment in patients with ASD is incompletely understood. It is also unknown how patients with knee arthroplasty and ASD compare to ASD patients with native knees.

Methods.

Baseline full-body radiographs were used, and hip and knee OA were graded by two independent reviewers using the KL classification. Spinopelvic parameters and PROMs were compared across the different knee OA groups and compared between patients with knee replacement and native knees.

Results.

199 patients with bilateral non severe OA (G1), 31 patients with unilateral severe knee OA (G2), and 60 patients with bilateral severe knee OA (G3). Patients with severe knee OA presented with worse spinopelvic parameters. However, after multivariable regression analysis controlling for age, frailty, PI, T1PA, knee OA was an independent predictor of knee flexion (G1:-0.02±7.3, G2: 7.8±9.4, G3: 4.5±8.7, P<0.001), and ankle dorsiflexion (G1: 2.3±4.0, G2: 6.6±4.5, G3: 5.1±4.1, P<0.001). There was no difference in PROMs (P>0.05). Secondary analysis included 96 patients: 48 patients (50%) with non-severe knee OA, and 48 patients (50%) with knee replacement. There was no difference in radiographic parameters or PROMs between the groups.

Conclusion.

In this study of complex ASD patients, patients with worse spinal deformity were more likely to have concomitant knee OA. Knee OA was shown to be a predictor of knee flexion and ankle dorsiflexion angles, but was not associated with worse PROMs in this study population. Patients with knee arthroplasty, however, had comparable spinal alignment and PROMs relative to those with mild OA.
Perioperative Considerations in Patients with Rett Syndrome as Compared to Those with Cerebral Palsy
Authors: Sarwahi Vishal , Rahman Effat , Eigo Katherine , Galina Jesse , Hasan Sayyida , Ko Andrew , Lo Yungtai , Amaral Terry , Djukic Aleksandra , Santiago Maria , Schneider James
Published: November 2024

Study Design.

Retrospective cohort study

Objective.

This study aimed to compare perioperative outcomes of Rett syndrome and Cerebral palsy patients undergoing posterior spinal fusion for neuromuscular scoliosis.

Summary of Background Data.

Surgical correction in the treatment of scoliosis for patients with Rett syndrome (RS) has been shown to increase survival rate. Cerebral palsy (CP) patients, like RS patients, are often nonverbal, nonambulatory, with frequent surgical complications.

Methods.

Retrospective review of 36 RS and 80 CP patients undergoing PSF from 2005-2023. Data and x-ray measurements were collected pre- and post-operatively. Sub-analysis was performed comparing non-ambulatory patients (GMFCS IV-V). Wilcoxon-Rank Sum, Fisher’s Exact, and Chi-square tests were utilized.

Results.

The primary outcome measure, complication rates, was similar between the groups (P=0.09). Preoperative Cobb angle, levels fused, fixation points, and LOS were similar (P>0.05). EBL was significantly higher in CP patients as was rate of transfusion (P=0.001) and surgical time (P=0.001). Postoperative Cobb angle (P=0.002) was significantly higher for CP patients. There was no significant difference between CP and RS patients in both preoperative (P=0.383) and postoperative (P=0.051) coronal decompensation. Nonambulatory status was associated with increased odds of having a postoperative complication (OR=6.17, 95% C.I. 1.36 – 28.04). Sub-analysis of non-ambulatory RS and CP patients revealed significantly higher postoperative Cobb (P=0.008), EBL (P=0.019) and surgical time (P=0.017) in CP patients compared to RS patients. There were no significant differences in preoperative Cobb, levels fused, fixation points, hospital stay, or complication rate (P>0.05).

Conclusion.

RS patients are shown to have better outcomes to CP patients in terms of surgical, perioperative, and radiographic variables. Ambulatory status was identified as an independent risk factor for complications.
Quantitative Validation of Hematocrit Percentage Drop Cutoff Points in Postpartum Hemorrhage: An Automated Gravimetric Approach
Authors: Kway Venance Basil , Rojas José Enrique Calacuayo , Cuevas Josué Sidonio Rodríguez , Moreno Ursula Medina , Juárez José Sergio Camacho , González Jorge Francisco Ayala , Larraga Karla Krebs , Martinez Ilse Veronica Castro , Reyther Roberto Arturo Castillo , Moscoso Antonio Gordillo
Published: November 2024

Objective:

To validate the hematocrit percentage drop cutoff points for blood loss in patients with postpartum hemorrhage (PPH) using the automated gravimetric method.

Methods:

A prospective cohort study was conducted from January 2023 to July 2023, in which 107 patients 18 years of age and above were scheduled for elective cesarean with obstetrical indications. We excluded cases with difficulty quantifying blood loss, those with incomplete data, and those of patients who did not consent to participate. Blood loss was measured by an automated gravimetric system integrated into a suction blood collector and surgical gauze weighing systems to automatically sum up blood loss immediately after hysterectomy and fetal delivery. The percentage drop in hematocrit was determined by subtracting the 8-hour postsurgical from presurgical hematocrit, divided by presurgical hematocrit. We performed the Pearson correlation test, and the receiver operating characteristic curve was used to determine cutoff points, their sensitivity, and their specificity. The κ index was used to determine the diagnostic agreement between the two methods.

Results:

A positive correlation was observed between the volume of blood loss and the percentage drop in hematocrit, with a Pearson correlation index of 0.70 and P < 0.0001. A 14% decrease in hematocrit had an 81.7% agreement rate, with a good κ index of 0.602, a sensitivity of 82.5%, and a specificity of 80.0%. A 10% drop in hemoglobin was sensitive (93.0%) but not very specific (56.0%) for blood loss greater than 1000 mL.

Conclusion:

The automated gravimetric method strongly correlates with hematocrit changes, providing an accurate real-time diagnosis of PPH. Additionally, a hematocrit percentage drop can retrospectively indicate significant blood loss, aiding in managing patients at risk for long-term PPH complications.
Platelet-derived mitochondria regulate lipid metabolism in nonalcoholic steatohepatitis through extracellular vesicles
Authors: Liao Tsai-Ling , Chen Der-Yuan , Hsieh Shie-Liang , Yang Ying-Ying , Chen Yi-Ming , Tang Kuo-Tung , Chang Chung-Hsin , Yang Sheng-Shun
Published: November 2024

Background and Aims:

Immune system activation, along with lipotoxicity due to excessive lipid droplet (LD) accumulation in the liver, are key drivers of NASH. Extracellular vesicles (EVs) released by cells that carry biological signals contribute to intercellular communication. However, the roles of immune cell–derived EVs in the pathogenesis of NASH are unclear.

Approach and Results:

Platelets are abundant in blood. We explored the role of platelet-derived EVs (pEVs) in LD accumulation from 30 patients with nonalcoholic fatty liver disease of different severity as well as 20 healthy subjects, a rat model, and an in vitro cell-based assay. There was increased platelet activation, accompanied by pEVs release, in NASH patients/rat model, and palmitate-treated cells. The mitochondria in the platelets and pEVs from NASH patients/rats were increased but dysfunctional, including a reduction in fatty acid β-oxidation, inactivated acetyl-CoA carboxylase 2, and suppressed oxidative phosphorylation system complex II/III/IV activity. These damaged mitochondria could be transferred to hepatocytes through pEVs to increase the number of lipid droplet–bound mitochondria. An increase in dysfunctional lipid droplet–bound mitochondria in hepatocytes affects lipid metabolism, resulting in excessive LD accumulation, elevated mitochondrial reactive oxygen species production, and apoptosis.

Conclusions:

We offer a novel molecular mechanism that connects platelets, pEVs, and excessive LD accumulation to the development of NASH. Our results suggest that NASH progression may be alleviated by specifically inhibiting the production and release of pEVs, or by targeting pEV components and inhibiting their uptake. Additional experiments are required to confirm this potentiality.
Human amniotic membrane overlay grafting for large retinal breaks in eyes with recurrent retinal detachment
Authors: Singh Deependra V , Reddy Raja R , Sharma Yog R
Published: November 2024

Purpose:

To describe a new technique for placing large epiretinal human amniotic membrane grafts in 2 eyes with high myopia and recurrent retinal detachment resulting from large breaks over staphyloma not amenable to laser or cryo retinopexy.

Methods:

Surgical technique demonstration with video and images. We examined 2 high myopic eyes with large retinal breaks and recurrent rhegmatogenous retinal detachment (RRD) who had undergone RRD repair with silicon oil tamponade. Break was seen over nasal staphyloma in first case and over an atrophic area along with retinoschisis at posterior pole in the second. 25G vitrectomy with silicon oil removal was done and a large multilayered hAM graft was placed over large retinal breaks. Both eyes receive Gas tamponade. The patients were positioned face down for the first week after surgery. Optical coherence tomography (OCT) scans were performed in the follow-up visits.

Results:

Retinal breaks could be successfully closed in both eyes at 2 weeks and 3 months follow up. Large hAM grafts were stable and nicely visualized on post operative OCT scans and fundus photographs. These grafts were well tolerated with no displacement even at 12 months follow up. There was no recurrence of RRD noted in either eye.

Conclusion:

The large overlay hAM grafting is an effective and safe technique for closing large retinal breaks over staphyloma or atrophic retina in high myopes.
Corneal Refractive Surgery Considerations in Patients With History of Orthokeratology
Authors: Wang Victoria M. , Moin Kayvon A. , Hoopes Phillip C. , Moshirfar Majid
Published: November 2024

Objective:

To review the current literature describing corneal changes observed with orthokeratology (ortho-k) use and to formulate preliminary recommendations for these patients seeking corneal refractive surgery.

Methods:

The literature search was conducted through the PubMed, Scopus, and Ovid databases through June 4, 2024, for articles regarding corneal physiological, tomographic, and biomechanical changes secondary to ortho-k use.

Results:

Forty-one articles were found describing several changes associated with ortho-k use, including higher corneal staining, central corneal epithelial thinning and midperipheral thickening, increased higher-order aberrations, decreased contrast sensitivity, reduced corneal hysteresis and corneal resistance factor, and alterations in the tear proteome. The majority of these parameters returned to baseline after ortho-k lens discontinuation, with timing potentially dependent on the amount of myopic correction, duration of ortho-k use, and age of lens fitting.

Conclusions:

Despite the paucity of articles describing prior ortho-k patients undergoing corneal refractive surgery, it is evident that ortho-k use may potentially cause various corneal physiological, tomographic, and biomechanical changes in patients. Therefore, clinicians are advised to serially monitor ortho-k patients' refraction, tomography, pachymetry, and corneal biomechanics until stability is achieved before considering surgery.
Enhancing Ex Vivo Limbal Epithelial Cell Expansion on Amniotic Membrane: A Comparative Study of Monolayer (2D) Versus Sandwich (3D) Culture Configurations
Authors: Kamachi Kobashigawa Karina , Franchi de Barros Sobrinho Alexandre Augusto , Espírito Santo Silva Paloma , Siqueira Vasconcelos Caio Rafael , Cardoso Cristovam Priscila , Pereira Gomes José Álvaro , Laus José Luiz , Aldrovani Rodrigues Marcela
Published: November 2024

Purpose:

This study compared two-dimensional (monolayer) and three-dimensional (sandwich) systems for expanding ex vivo limbal epithelial cells on amniotic membrane and evaluated the outcomes after transplantation into rabbits with experimentally induced limbal stem cell deficiency.

Methods:

Evaluations included markers for progenitor cells, proliferation, apoptosis, and clinical monitoring for up to 63 days. In the monolayer culture, epithelial cells derived from limbal explants were expanded on amniotic membrane as the substrate. In the sandwich culture, the cells were cultured between 2 layers of amniotic membrane. Evaluations included markers for progenitor cells, proliferation, and apoptosis, along with clinical monitoring for up to 63 days.

Results:

Sandwich cultures demonstrated increased cellular proliferation and fewer progenitor cells compared with monolayer cultures. In treating limbal stem cell deficiency, the group receiving transplantation from sandwich cultures exhibited reduced neovascularization and decreased corneal ulceration compared with those treated with monolayer cultures, with similar clinical outcomes in corneal opacity. The configuration of the culture system did not affect the presence of apoptotic cells. Corneas treated with sandwich cultures showed a higher presence of progenitor cells compared with the monolayer group, suggesting a potential long-term viability advantage for these transplants.

Conclusions:

In conclusion, although the sandwich culture system enhanced cellular proliferation, it also resulted in a decrease in progenitor cells within the cultures. Nevertheless, both systems demonstrated comparable therapeutic efficacy in treating limbal stem cell deficiency, with the sandwich approach potentially offering long-term benefits because of the increased presence of progenitor cells in the transplanted cornea.
Overlap syndrome: a case series and literature review of concurrent pigment dispersion and pseudoexfoliation syndromes
Authors: Shah Pooja , Soundararajan Srinath , Fleischman David
Published: November 2024

Purpose of review

The purpose of this review is to present two cases of overlap syndrome, or concurrent pigment dispersion syndrome and pseudoexfoliation syndrome. The summary of existing literature highlights the importance of accurate diagnosis and potential treatment options of overlap syndrome.

Recent findings

The cases describe two patients with overlap syndrome and resulting progressive glaucoma. The condition tends to present after age 50 years old, with presence of both pseudoexfoliative material and pigment dispersion signs. The pigment dispersion syndrome may be quiescent at the time of pseudoexfoliation onset and may have gone undiagnosed. This form of glaucoma poses challenges in controlling intraocular pressure and may progress rapidly, often requiring surgical intervention.

This paper reviews the common examination findings of pigment dispersion syndrome and pseudoexfoliation, which may aid clinicians in the diagnosis of the rare condition, overlap syndrome. The connection between the two conditions remains unclear, though studies of possible genetic associations are underway. The two-hit theory, or initial damage to the trabecular meshwork increasing susceptibility to future damage, is plausible given the severe nature of the condition. Though definitive conclusions regarding treatment strategies and outcomes of overlap syndrome are lacking, increased awareness, diagnosis, and study of the condition may help guide the management of overlap syndrome.
Prevention of cardiometabolic diseases through dietary modifications
Authors: Chávez-Alfaro Lourdes , Silveira-Sanguino Víctor , Piernas Carmen
Published: November 2024

Purpose of review

Cardiometabolic diseases (CMDs) increasingly contribute to the cumulative burden of morbidity and mortality worldwide. Here, we reviewed intervention studies using a randomized controlled trial (RCT) design as well as meta-analyses of RCTs aimed at testing the effectiveness of different dietary approaches for CMD prevention.

Recent findings

Recent studies testing dietary approaches for CMD prevention were summarized narratively, with a focus on interventions based on caloric restriction and fasting, healthy dietary patterns and food-based dietary modifications. Evidence supports intermittent fasting, Mediterranean, Nordic, DASH, low-carbohydrate/ketogenic and plant-based diets as effective strategies for improving cardiometabolic health. However, the benefits observed with some of these dietary patterns are linked to energy restriction, and the independent effects beyond weight loss remain unclear. The effectiveness of some strategies may also depend on the overall dietary quality and adherence to the programme.

Recent findings highlight the importance of focusing on overall dietary patterns, rather than isolated nutrients, for preventing CMD. Future research should prioritize long-term intervention studies to assess the sustained effects of these dietary patterns on CMD outcomes.
Treatment of spinal muscular atrophy
Authors: Pera Maria Carmela , Mercuri Eugenio
Published: November 2024

Purpose of review

The aim of the review was to provide an overview of safety and efficacy of the available treatments including information from both clinical trials and real-world data. Additional information form ongoing studies using other approaches than increasing SMN protein are also reported.

Recent findings

In the last 3 years, there have been over 24 studies reporting safety and the impact of the available drugs on different aspects of function, including respiratory and bulbar function. These findings, obtained in a real-world setting, are extremely important to define the spectrum of responses in individuals with different age, weight, SMN2 copies, and other variables and will be of help to the families and the clinicians to set up the right expectations at the time of starting a new treatment.

The large number of studies that became available in the last few years support and expand the information on safety and efficacy provided by the clinical trials.