Functional diversity among cardiolipin binding sites on the mitochondrial ADP/ATP carrier.

Lipid-protein interactions play a multitude of essential roles in membrane homeostasis. Mitochondrial membranes have a unique lipid-protein environment that ensures bioenergetic efficiency. Cardiolipin (CL), the signature mitochondrial lipid, plays multiple roles in promoting oxidative phosphorylation (OXPHOS). In the inner mitochondrial membrane, the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) exchanges ADP and ATP, enabling OXPHOS. AAC/ANT contains three tightly bound CLs, and these interactions are evolutionarily conserved. Here, we investigated the role of these buried CLs in AAC/ANT using a combination of biochemical approaches, native mass spectrometry, and molecular dynamics simulations. We introduced negatively charged mutations into each CL-binding site of yeast Aac2 and established experimentally that the mutations disrupted the CL interactions. While all mutations destabilized Aac2 tertiary structure, transport activity was impaired in a binding site-specific manner. Additionally, we determined that a disease-associated missense mutation in one CL-binding site in human ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions.

A Comparative Evaluation of Unilateral and Bilateral Sequential Lung Isolation for Vertebral Body Tethering: A Retrospective Propensity Matched Analysis.

BACKGROUND: Vertebral body tethering (VBT) requires a thoracoscopic approach to visualize the vertebral bodies. Lung collapse and re-expansion have the potential to cause acute lung injury, resulting in increased oxygen and ventilation requirements. AIMS: We compared the intraoperative ventilator management, intra- and postoperative blood gas determinations, and hospital stay information between adolescents undergoing unilateral versus bilateral lung isolation for vertebral body tethering. METHODS:  A study cohort of 132 propensity-matched cases (66 unilateral and 66 bilateral) was derived from 351 consecutive VBT cases. Patient demographic information, case information, fluid administration, ventilatory settings data, blood gas parameters, and complete blood count and differential data were entered into a datasheet. Derived parameters included values calculated from the alveolar gas equation to develop an oxygen cascade and measures of inflammatory response. Chi-square was used for categorical data, and independent samples and t-tests were used for continuous data. RESULTS: The double lung isolation group required higher peak inspiratory pressures (SL 29±5 vs. DL 31±5, p=0.026), resulting in higher tidal volume (SL 246±63 vs. DL 334±101, p<0.001) and tidal volume per kg (SL 5.6±1.4 vs. DL 6.9±2, p<0.001) as compared to the single lung group. The double lung group required a higher partial pressure of inspired and alveolar oxygen as well as a higher alveolar to arterial oxygen tension gradient (SL 417±126 vs. DL 485±96, p=0.001) to achieve optimal arterial oxygen tension. Patients with double lung isolation had similar intensive care lengths of stay but a longer hospital stay than single lung isolation patients. CONCLUSION: Patients undergoing double lung isolation required greater ventilatory support and had more evidence of acute lung injury, as evidenced by a higher postoperative alveolar to arterial oxygen gradient; however, these healthy adolescents tolerated the procedure well and only differed in the hospital length of stay by a day.

Hydropneumopericardium Due to a Traumatic Esophageal-Pericardial Fistula.

Esophago-pericardial fistula is a rare, life-threatening condition, usually arising as a complication of benign esophageal disorders or iatrogenic causes. Prompt diagnosis via multimodality imaging is crucial, with computed tomography being the most sensitive. Management varies based on severity, with a growing trend toward early endoscopic interventions, which result in improved outcomes.

Sleep Apnea and Heart Failure-Current State-of-The-Art.

Sleep-disordered breathing (SDB), including obstructive and central sleep apnea, significantly exacerbates heart failure (HF) through adverse cardiovascular mechanisms. This review aims to synthesize existing literature to clarify the relationship between SDB and HF, focusing on the pathophysiological mechanisms, diagnostic challenges, and the effectiveness of treatment modalities like continuous positive airway pressure (CPAP) and adaptive servo-ventilation ASV. We analyzed peer-reviewed articles from 2003 to 2024 sourced from PubMed, EMBASE, Scopus, and Web of Science databases. The prevalence of SDB in HF patients is high, often underdiagnosed, and underappreciated. Management strategies, including CPAP and ASV, have been shown to mitigate symptoms and improve cardiac function. However, despite the availability of effective treatments, significant challenges in screening and diagnosis persist, affecting patient management and outcomes. DB significantly impacts HF prognosis. Enhanced screening strategies and broader utilization of therapeutic interventions like CPAP and ASV are essential to improve the management and outcomes of HF patients with concomitant SDB. Future research should focus on refining diagnostic and treatment protocols to optimize care for HF patients with SDB.

Nanocellulose-assisted mechanically tough hydrogel platforms for sustained drug delivery.

The controlled delivery of the desired bioactive molecules is required to achieve the maximum therapeutic effects with minimum side effects. Biopolymer-based hydrogels are ideal platforms for delivering the desired molecules owing to their superior biocompatibility, biodegradability, and low-immune response. However, the prolonged delivery of the drugs through biopolymer-based hydrogels is restricted due to their weak mechanical stability. We developed mechanically tough and biocompatible hydrogels to address these limitations using carboxymethyl chitosan, sodium alginate, and nanocellulose for sustained drug delivery. The hydrogels were cross-linked through calcium ions to enhance their mechanical strength. Nanocellulose-added hydrogels exhibited improved mechanical strength (Young's modulus; 23.36 â†’ 30.7 kPa, Toughness; 1.39 â†’ 5.65 MJm-3) than pure hydrogels. The composite hydrogels demonstrated increased recovery potential (66.9 â†’ 84.5 %) due to the rapid reformation of damaged polymeric networks. The hydrogels were stable in an aqueous medium and demonstrated reduced swelling potential. The hydrogels have no adverse effects on embryonic murine fibroblast (3 T3), showing their biocompatibility. No bacterial growth was observed in hydrogels-treated groups, indicating their antibacterial characteristics. The sustained drug released was observed from nanocellulose-assisted hydrogel scaffolds compared to the pure polymer hydrogel scaffold. Thus, hydrogels have potential and could be used as a sustained drug carrier.

Functional Magnetic Resonance Spectroscopy of Prolonged Motor Activation using Conventional and Spectral GLM Analyses.

Background: Functional MRS (fMRS) is a technique used to measure metabolic changes in response to increased neuronal activity, providing unique insights into neurotransmitter dynamics and neuroenergetics. In this study we investigate the response of lactate and glutamate levels in the motor cortex during a sustained motor task using conventional spectral fitting and explore the use of a novel analysis approach based on the application of linear modelling directly to the spectro-temporal fMRS data. Methods: fMRS data were acquired at a field strength of 3 Tesla from 23 healthy participants using a short echo-time (28ms) semi-LASER sequence. The functional task involved rhythmic hand clenching over a duration of 8 minutes and standard MRS preprocessing steps, including frequency and phase alignment, were employed. Both conventional spectral fitting and direct linear modelling were applied, and results from participant-averaged spectra and metabolite-averaged individual analyses were compared. Results: We observed a 20% increase in lactate in response to the motor task, consistent with findings at higher magnetic field strengths. However, statistical testing showed some variability between the two averaging schemes and fitting algorithms. While lactate changes were supported by the direct spectral modelling approach, smaller increases in glutamate (2%) were inconsistent. Exploratory spectral modelling identified a 4% decrease in aspartate, aligning with conventional fitting and observations from prolonged visual stimulation. Conclusion: We demonstrate that lactate dynamics in response to a prolonged motor task are observed using short-echo time semi-LASER at 3 Tesla, and that direct linear modelling of fMRS data is a useful complement to conventional analysis. Future work includes mitigating spectral confounds, such as scalp lipid contamination and lineshape drift, and further validation of our novel direct linear modelling approach through experimental and simulated datasets.

Wide Complex Tachycardia in a Middle-Aged Woman With Diarrhea.

A woman in her mid-60s with a history of paroxysmal atrial fibrillation and hypertension presents with 3 days of nausea, vomiting, and diarrhea. What would you do next?

B0-insensitive image navigators for prospective motion-corrected MRS with localized second-order shimming.

PURPOSE: Localized shimming in single-voxel MRS often results in large B0 inhomogeneity outside the volume-of-interest. This causes unacceptable degradation in motion navigator images. Switching back and forth between whole-brain shim and localized shim is possible for linear shims, but not for higher-order shims. Here we propose motion navigators largely insensitive to B0 inhomogeneity for prospective motion-corrected MRS with localized higher-order shimming. METHODS: A recent fast high-resolution motion navigator based on spiral-in/out k-space trajectories and multislice-to-volume registration was modified by splitting the readout into multiple shot interleaves which shortened the echo time and reduced the effect of B0 inhomogeneity. The performance of motion correction was assessed in healthy subjects in the prefrontal cortex using a sLASER sequence at 3T (N = 5) and 7T (N = 5). RESULTS: With multiple spatial interleaves, excellent quality navigator images were acquired in the whole brain in spite of large B0 inhomogeneity outside the MRS voxel. The total duration of the navigator in sLASER remained relatively short even with multiple shots (3T: 10 spatial interleaves 94 ms per slice; 7T: 15 spatial interleaves 103 ms per slice). Prospective motion correction using the multi-shot navigators yielded comparable spectral quality (water linewidth and metabolite SNR) with and without subject motion. CONCLUSION: B0-insensitive motion navigators enable prospective motion correction for MRS with all first- and second-order shims adjusted in the MRS voxel, providing optimal spectral linewidth.

Induced electric fields inhibit breast cancer growth and metastasis by modulating the immune tumor microenvironment.

Despite tremendous advances in oncology, metastatic triple-negative breast cancer remains difficult to treat and manage with established therapies. Here, we show in mice with orthotopic triple-negative breast tumors that alternating (100 kHz), and low intensity (<1 mV/cm) induced electric fields (iEFs) significantly reduced primary tumor growth and distant lung metastases. Non-contact iEF treatment can be delivered safely and non-invasively in vivo via a hollow, rectangular solenoid coil. We discovered that iEF treatment enhances anti-tumor immune responses at both the primary breast and secondary lung sites. In addition, iEF reduces immunosuppressive TME by reducing effector CD8+ T cell exhaustion and the infiltration of immunosuppressive immune cells. Furthermore, iEF treatment reduced lung metastasis by increasing CD8+ T cells and reducing immunosuppressive Gr1+ neutrophils in the lung microenvironment. We also observed that iEFs reduced the metastatic potential of cancer cells by inhibiting epithelial-to-mesenchymal transition. By introducing a non-invasive and non-toxic electrotherapeutic for inhibiting metastatic outgrowth and enhancing anti-tumor immune response in vivo, treatment with iEF technology could add to a paradigm-shifting strategy for cancer therapy.

Persistent chronic calcific pancreatitis with intraductal calculi associated with secondary diabetes mellitus type 3 and diabetic ketoacidosis - A case report.

Diabetes mellitus type 3 refers to diabetes secondary to an existing disease or condition of the exocrine pancreas and is an uncommon cause of diabetes occurring due to pancreatogenic pathology. It accounts for 15-20% of diabetic patients in Indian and Southeast Asian continents. This is case report of a rare case of type 3 diabetes mellitus (T3DM) presenting with diabetic ketoacidosis (DKA). The patient was admitted for DKA along with complaint of hyperglycemia, blood glucose of 405 mg/dl with HbA1c level of 13.7%. Computed tomography evidence revealed chronic calcific pancreatitis with intraductal calculi and dilated pancreatic duct.

Role of marination, natural antimicrobial compounds, and packaging on microbiota during storage of chicken tawook.

The aim of this study was to investigate the antimicrobial effect of marination, natural antimicrobials, and packaging on the microbial population of chicken tawook during storage at 4°C. Chicken meat was cut into 10 g cubes and marinated. The chicken was then mixed individually with 0.5% or 1% (w/v) vanillin (VA), ß-resorcylic acid (BR), or eugenol (EU), and stored under aerobic (AP) or vacuum (VP) packing at 4°C for 7 d. The marinade decreased microbial growth as monitored by total plate count, yeast and mold, lactic acid bacteria, and Pseudomonas spp. by about 1 log cfu/g under AP. The combination of marinade and antimicrobials under AP and VP decreased growth of spoilage-causing microorganisms by 1.5 to 4.8 and 2.3 to 4.6 log cfu/g, respectively. Change in pH in VP meat was less than 0.5 in all treated samples including the control. Marination decreased the lightness of the meat (L*) and significantly (p < 0.05) increased the redness (A*) and yellowness (B*). Overall acceptability was highest for marinated samples with 0.5% BR.

Development of miRNA-SSR and target-SSR markers from yield-associate genes and their applicability in the assessment of genetic diversity and association mapping in rice (Oryza sativa L.).

The gene-derived functional markers are considered effective to use in marker-assisted breeding and genetic diversity analysis. As of now, no functional markers have been identified from miRNAs regulating yield traits. The miRNAs play a key role as regulators in controlling the candidate genes involved in grain yield improvement in rice. In this study, 13 miRNA-SSR and their target gene SSR markers were mined from 29 yield-responsive miRNA along with their 29 target genes in rice. The validation of these markers showed that four miRNA-SSRs and one target gene SSR markers had shown polymorphism among 120 diverse rice genotypes. The PIC values ranged from 0.25 (OsARF18-SSR) to 0.72 (miR408-SSR, miR172b-SSR, and miR396f-SSR) with an average value of 0.57. These polymorphic markers grouped 120 rice genotypes into 3 main clusters based on the levels of high genetic diversity. These markers also showed significant association with key yield traits. Among all, miR172b-SSR showed a strong association with plant height in two seasons. This investigation suggests that this new class of molecular markers has great potential in the characterization of rice germplasm by genetic diversity and population structure and in marker-assisted breeding for the development of high-yielding varieties. Supplementary information: The online version contains supplementary material available at 10.1007/s11032-024-01462-z.

Unzipped carbon nanotubes assisted 3D printable functionalized chitosan hydrogels for strain sensing applications.

Developing multifunctional hydrogels for wearable strain sensors has received significant attention due to their diverse applications, including human motion detection, personalized healthcare, soft robotics, and human-machine interfaces. However, integrating the required characteristics into one component remains challenging. To overcome these limitations, we synthesized multifunctional hydrogels using carboxymethyl chitosan (CMCS) and unzipped carbon nanotubes (f-CNTs) as strain sensor via a one-pot strategy. The polar groups in CMCS and f-CNTs enhance the properties of the hydrogels through different interactions. The hydrogels show superior printability with a uniformity factor (U) of 0.996 ± 0.049, close to 1. The f-CNTs-assisted hydrogels showed improved storage modulus (8.8 × 105 Pa) than the pure polymer hydrogel. The hydrogels adequately adhered to different surfaces, including human skin, plastic, plastic/glass interfaces, and printed polymers. The hydrogels demonstrated rapid self-healing and good conductivity. The biocompatibility of the hydrogels was assessed using human fibroblast cells. No adverse effects were observed with hydrogels, showing their biocompatibility. Furthermore, hydrogels exhibited antibacterial potential against Escherichia coli. The developed hydrogel exhibited unidirectional motion and complex letter recognition potential with a strain sensitivity of 2.4 at 210 % strain. The developed hydrogels could explore developing wearable electronic devices for detecting human motion.

Dosimetric comparison of O-ring versus conventional C-arm linear accelerator for volumetric modulated arc therapy (VMAT) of head and neck cancer and carcinoma cervix patients.

The objective of this study is dosimetric comparison between the O-ring Halcyon and C-arm Clinac iX linac for volumetric modulated arc therapy (VMAT) plans for head & neck (H&N) cancer and carcinoma cervix patients. Total 60 patients of H&N cancer and carcinoma cervix were enrolled prospectively from March 2021 to March 2023. VMAT plans with 6 MV photons for Halcyon and Clinac iX were generated and compared for each patient by dose volume histogram for planning target volume coverage and organ at risk (OAR) sparing. There were no differences in between both the linacs for PTV D2% and D98%, homogeneity index, conformity index, Dmax (maximum dose) and Dmean (mean dose) of OAR. Halcyon had significantly shorter treatment time compared to Clinac iX. Halcyon delivered higher integral dose and monitor units. O-ring Halcyon produces VMAT plans comparable to other C-arm linacs for H&N and carcinoma cervix patients.

Discovery and description of a new species of burrowing frog Sphaerotheca Gnther, 1859 (Anura: Dicroglossidae) from the suburban landscapes of Bengaluru, India.

Recent resolution of prevailing taxonomic ambiguities in the genus Sphaerotheca and new species discoveries from urban/suburban landscapes highlight the need for attention to non-forested habitats for amphibian conservation. In this paper, we review the status of the members of the genus Sphaerotheca and justify the synonymy of Sphaerotheca magadha as a junior synonym of Sphaerotheca swani. The prospects of resurrection of Sphaerotheca swani (herein preliminarily referred to as Sphaerotheca cf. breviceps [swani]) are discussed. In addition, we describe a new species Sphaerotheca varshaabhu sp. nov. from the suburban region of Bengaluru, India. We employ an integrative taxonomic approach to characterize the new species using molecular phylogeny, genetic distance, morphological characters, and geographical isolation as lines of evidence. We also provide a description of vocal repertoire of Sphaerotheca varshaabhu sp. nov. and provide comparative bioacoustics data for four species. This previously undescribed species from the suburban areas of Bengaluru described herein as Sphaerotheca varshaabhu sp. nov. forms a genetically divergent lineage and its genetic distance varied from 3.6% to 12.2% for 16S rRNA with respect to other species of Sphaerotheca. Our phylogenetic analysis for the genus including the new species confirms the synonymy of one recently described species, resulting in 10 valid species in the genus Sphaerotheca. These results emphasize the need for utilizing an integrative taxonomic approach for uncovering hidden diversity of suburban areas. Given these recent discoveries, we advocate for more robust surveys in human dominated areas, so that these amphibians may receive more attention.

Recurrent central odontogenic fibroma in a patient with nevoid basal cell carcinoma syndrome: case report and in vitro analysis.

OBJECTIVE: Central odontogenic fibromas (COF) are rare, benign tumors derived from dental mesenchymal tissue that may occur in the maxilla or mandible. This report describes primary and recurrent COF in the mandible of a patient with nevoid basal cell carcinoma syndrome (NBCCS). STUDY DESIGN: A 36-year-old African American male presented with a COF and its recurrence 17 months later. Tissue pieces were obtained from both occurrences with IRB-approved signed consent. Collected tissue pieces were dissected; one portion was formalin-fixed and paraffin-embedded, and the other was cultured for the isolation of cell populations from the primary (COdF-1) and recurrent (COdF-1a) tumors. Quantification real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and DNA sequencing were used for gene and protein analysis of the primary tumor and cell populations. RESULTS: Histopathologic analysis of the tumor showed sparse odontogenic epithelial cords in fibrous connective tissue, and qRT-PCR analysis of tumor and cell populations (COdF-1 and COdF-1a) detected VIM, CK14, CD34, CD99 and ALPL mRNA expression. Protein expression was confirmed by immunohistochemistry. CD34 expression in primary tissues was higher than in tumor cells due to tumor vascularization. DNA sequencing indicated the patient had PTCH1 mutations. CONCLUSIONS: Histopathology, mRNA, and protein expression indicate the rare occurrence of COF in a patient with mutated PTCH1 gene and NBCCS.

A computational strategy for estimation of mean using optimal imputation in presence of missing observation.

In this study, we suggest an optimal imputation strategy for the elevated estimation of the population mean of the primary variable utilizing the known auxiliary parameters for the missing observations. Under this strategy, we suggest a new modified Searls type estimator, and we study its sampling properties, mainly bias and mean squared error (MSE), for an approximation of order one. The introduced estimator is compared theoretically with the estimators of population mean in competition under the imputation method. The efficiency conditions for the introduced estimator to be more efficient than the estimators in the competition are derived. To be sure about the efficiencies, these efficiency conditions are verified through the three natural populations. We have also conducted a simulation study and generated an artificial population with the same parameters as a natural population. The estimator with minimum MSE and the highest Percentage Relative Efficiency (PRE) is recommended for practical use in different areas of applications.

Speech and Swallowing Outcomes of Surgically Managed Cervical Chordoma: A Case Series.

OBJECTIVES: Cervical chordoma is a rare, low-grade primary bone tumor occurring in the axial skeleton. Due to challenges in surgical exposure caused by anatomic location, patients may experience dysfunction in speech and swallowing. The objective of this study was to characterize speech and swallowing outcomes for patients undergoing surgical resection of cervical chordoma. Moreover, we detail in-depth two cases with similar initial presentations to compare prognostic factors and management strategies. METHODS: Eleven patients with histologically confirmed cervical chordoma treated between 1993 and 2020 were included in this retrospective case series. Outcomes measured included overall survival, disease-free survival, need for enteral feeds, as well as results of modified barium swallow study (MBSS) and fiberoptic laryngoscopy. RESULTS: The mean age at diagnosis was 55.9 years. The patient population was 81.8% male. Mean survival after diagnosis was 96 months. Four (36.4%) patients required post-operative MBSS and demonstrated aspiration. All four of these patients presented with tumors in the superior cervical spine and received surgeries utilizing anterior approaches. Of the four, 2 required enteral feeds long-term. Four (36.4%) patients endorsed dysphonia. One patient developed post-operative right vocal fold paresis. The remaining three patients experienced stable dysphonia pre- and post-operatively. Additionally, three (27%) patients required tracheostomy placement, two of which remained in place long-term. CONCLUSIONS: Dysphagia is a common side effect of cervical chordoma resection. It is associated with the use of an anterior approach during resection and with tumors located in the superior cervical spine. Patients with postoperative dysphagia should receive early multidisciplinary swallow rehabilitation. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Register transitions in an in vivo canine model as a function of intrinsic laryngeal muscle stimulation, fundamental frequency, and sound pressure level.

Phonatory instabilities and involuntary register transitions can occur during singing. However, little is known regarding the mechanisms which govern such transitions. To investigate this phenomenon, we systematically varied laryngeal muscle activation and airflow in an in vivo canine larynx model during phonation. We calculated voice range profiles showing average nerve activations for all combinations of fundamental frequency (F0) and sound pressure level (SPL). Further, we determined closed-quotient (CQ) and minimum-posterior-area (MPA) based on high-speed video recordings. While different combinations of muscle activation favored different combinations of F0 and SPL, in the investigated larynx there was a consistent region of instability at about 400 Hz which essentially precluded phonation. An explanation for this region may be a larynx specific coupling between sound source and subglottal tract or an effect based purely on larynx morphology. Register transitions crossed this region, with different combinations of cricothyroid and thyroarytenoid muscle (TA) activation stabilizing higher or lower neighboring frequencies. Observed patterns in CQ and MPA dependent on TA activation reproduced patterns found in singers in previous work. Lack of control of TA stimulation may result in phonation instabilities, and enhanced control of TA stimulation may help to avoid involuntary register transitions, especially in the singing voice.