Qualitative analysis of the Supraspinatus muscle fatty infiltration on MRI - Correlation of the Tangent sign with Goutallier grade at the Y view and Medial Scapular border in large retracted rotator cuff tears.

BACKGROUND: Surgically repairing rotator cuff tears with a higher extent of fatty infiltration is controversial. Current evidence supports performing rotator cuff repair in patients exhibiting Goutallier stage 3-4 fatty infiltration. However, the presence of retraction complicates accurate assessment using the Goutallier Classification, particularly on the lateral Y-view. A shift towards classifying fatty infiltration in more medial regions may enhance the precision of tissue quality quantification. The objective of this study was to analyze the uniformity of fatty infiltration within the entire supraspinatus muscle using the Goutallier Classification across three scapular Y-view sections and to examine the association between Goutallier grade, tangent sign, and modified Patte stage. METHODS: A retrospective evaluation was conducted on preoperative magnetic resonance imaging (MRI) scans from a consecutive series of 97 patients who had previously undergone arthroscopic rotator cuff repairs. Three supraspinatus sections on the MRI sagittal plane were identified: the lateral Y-view (section one), a medial section at the suprascapular notch anatomical landmark (section two), and a section 3 cm medial from the suprascapular notch Medial Scapular Body (section three). Goutallier grade, tangent sign, and modified Patte stage were used to evaluate fatty infiltration, muscle atrophy, and tendon retraction, respectively. RESULTS: Section one had the highest Goutallier grade, while section three had the lowest. Intra-observer rest retest reliability analysis showed excellent consistency in all sections with section one (ICC=0.920, 95% CI), section two (ICC=0.917, 95% CI), and section three (ICC=0.923, 95% CI) for Goutallier grade. Inter-observer reliability analysis also revealed excellent consistency in sections one (ICC=0.951, 95% CI), section two (ICC=0.949, 95% CI), and section three (ICC=0.922, 95% CI) for Goutallier grade. A strong correlation was observed between Goutallier grade and modified Patte stage (τb=0.43-0.56, p=0.001), and between Goutallier grade and tangent sign (τb=0.43-0.54, p=0.001) across all sections. CONCLUSION: The severity of fatty infiltration within the supraspinatus muscle belly is inconsistent, with the lateral portion being the most severe and the medial portion the least severe. Goutallier grade demonstrates a strong correlation with tangent sign and modified Patte stage. This suggests that tendon retraction results in a potential overestimation in the amount of fatty infiltration defining some tears unjustly irreparable when measuring at the traditionally described lateral Y-view position compared with 3cm medial.

Assessment of Psychiatric Illness among Pulmonary Tuberculosis Patients at a Tertiary Care Center in India.

INTRODUCTION: Tuberculosis (TB) is a chronic infectious multisystemic disease caused by Mycobacterium tuberculosis and is one of the leading causes of mortality worldwide. Both common mental disorders (CMD) and TB are global public health problems that have a considerable impact on human health. Moreover, TB and CMDs share common risk factors including poverty, drug addiction, and homelessness and the coexistence of CMD and TB leads to difficult management of TB. MATERIALS AND METHODS: This was a hospital-based longitudinal study, carried out between June 2021 and December 2022. In this study, 147 pulmonary TB patients were included as per inclusion and exclusion criteria, and psychiatric illness was evaluated by the Brief Psychiatric Rating Scale. RESULTS: The mean age of study participants was 37.59 ± 15.37 years, there were 99 (67.3%) were male and 48 (32.7%) were female. Psychiatric illness was found in 77 (52.38%) pulmonary TB patients. Among psychiatric illness, anxiety was found in 33 (22.4%) participants and 21 (14.3%) participants had depression. Mixed anxiety and depression were found in 20 (13.6%) patients and 03 (2%) participants had severe psychosis. The association of psychiatric illness with age group and gender was not significant (P = 0.734, 0.203, respectively). There were 105 (71.40%) patients who had <12 standard education and 42 (28.60%) had >12 standard education and their association with psychiatric illness was statistically significant (P = 0.044). Adverse drug reactions were found among 80 (54.42%) patients and the association between adverse drug reactions and psychiatric illness was significant (P = 0.031). CONCLUSION: Psychiatric illness is one of the important domains to be evaluated in timely manner in TB patients and early intervention is needed for better management of the TB because the severity, social factors, and chronicity of the disease make them susceptible to develop psychiatric illness.

Résumé Introduction:La tuberculose (TB) est une maladie infectieuse multisystémique chronique causée par Mycobacterium tuberculosis et constitue l'une des principales causes de mortalité dans le monde. Les troubles mentaux courants (CMD) et la tuberculose sont des problèmes de santé publique mondiaux qui ont un impact considérable sur la santé humaine. De plus, la tuberculose et les troubles mentaux courants (CMD) partagent des facteurs de risque communs, notamment la pauvreté, la toxicomanie et l'itinérance, et la coexistence des CMD et de la tuberculose rend difficile la gestion de la tuberculoseMéthodes:Il s'agissait d'une étude longitudinale en milieu hospitalier, réalisée entre juin 2021 et décembre 2022. Dans cette étude, 147 patients atteints de tuberculose pulmonaire ont été inclus selon les critères d'inclusion et d'exclusion et la maladie psychiatrique a été évaluée par une brève échelle d'évaluation psychiatrique (BPRS)Résultats:L'âge moyen des participants à l'étude était de 37,59 ± 15,37 ans, il y avait 99 (67,3 %) hommes et 48 (32,7 %) femmes. Une maladie psychiatrique a été trouvée chez 77 (52,38 %) patients atteints de tuberculose pulmonaire. Parmi les maladies psychiatriques, l'anxiété a été constatée chez 33 (22,4 %) participants et 21 (14,3 %) participants souffraient de dépression. Une anxiété et une dépression mixtes ont été trouvées chez 20 (13,6 %) patients et 03 (2 %) participants souffraient d'une psychose sévère. L'association entre la maladie psychiatrique et le groupe d'âge et le sexe n'était pas significative (valeur P = 0,734, 0,203 respectivement). Il y avait 105 (71,40 %) patients ayant <12 niveaux d'éducation standard et 42 (28,60 %) avaient >12 niveaux d'éducation standard et leur association avec une maladie psychiatrique était statistiquement significative (P = 0,044). Des effets indésirables du médicament ont été observés chez 80 (54,42 %) patients et l'association entre l'effet indésirable du médicament et la maladie psychiatrique était significative. (P = 0,031)Conclusion:La maladie psychiatrique est l'un des domaines importants à évaluer en temps opportun chez les patients tuberculeux et une intervention précoce est nécessaire pour une meilleure prise en charge de la tuberculose car la gravité, les facteurs sociaux et la chronicité de la maladie les rendent susceptibles de développer une maladie psychiatrique.

Diffusion Tensor Imaging in Boys With Adrenoleukodystrophy: Identification of Cerebral Disease and Association With Neurocognitive Outcomes.

BACKGROUND AND OBJECTIVES: Childhood cerebral adrenoleukodystrophy (C-ALD) is a severe inflammatory demyelinating disease that must be treated at an early stage to prevent permanent brain injury and neurocognitive decline. In standard clinical practice, C-ALD lesions are detected and characterized by a neuroradiologist reviewing anatomical MRI scans. We aimed to assess whether diffusion tensor imaging (DTI) is sensitive to the presence and severity of C-ALD lesions and to investigate associations with neurocognitive outcomes after hematopoietic cell therapy (HCT). METHODS: In this retrospective cohort study, we analyzed high-resolution anatomical MRI, DTI, and neurocognitive assessments from boys with C-ALD undergoing HCT at the University of Minnesota between 2011 and 2021. Longitudinal DTI data were compared with an age-matched group of boys with ALD and no lesion (NL-ALD). DTI metrics were obtained for atlas-based regions of interest (ROIs) within 3 subdivisions of the corpus callosum (CC), corticospinal tract (CST), and total white matter (WM). Between-group baseline and slope differences in fractional anisotropy (FA) and axial (AD), radial (RD), and mean (MD) diffusivities were compared using analysis of covariance accounting for age, MRI severity (Loes score), and lesion location. RESULTS: Among patients with NL-ALD (n = 14), stable or increasing FA, stable AD, and stable or decreasing RD and MD were generally observed during the 1-year study period across all ROIs. In comparison, patients with mild posterior lesions (Loes 1-2; n = 13) demonstrated lower baseline FA in the CC splenium (C-ALD 0.50 ± 0.08 vs NL-ALD 0.58 ± 0.04; pBH = 0.022 adjusted Benjamini-Hochberg p-value), lower baseline AD across ROIs (e.g., C-ALD 1.34 ± 0.03 ×10-9 m2/s in total WM vs NL-ALD 1.38 ± 0.04 ×10-9 m2/s; pBH = 0.005), lower baseline RD in CC body and CST, and lower baseline MD across ROIs except CC splenium. Longitudinal slopes in CC splenium showed high sensitivity and specificity in differentiating early C-ALD from NL-ALD. Among all patients with C-ALD (n = 38), baseline Loes scores and DTI metrics were associated with post-HCT neurocognitive functions, including processing speed (e.g., FA WM Spearman correlation coefficient R = 0.64) and visual-motor integration (e.g., FA WM R = 0.71). DISCUSSION: DTI was sensitive to lesion presence and severity as well as clinical neurocognitive effects of C-ALD. DTI metrics quantify C-ALD even at an early stage.

Secondary failure of lentiviral vector gene therapy in a cerebral adrenoleukodystrophy patient with an ABCD1 whole-gene deletion.

A 9-year-old boy with adrenoleukodystrophy due to ABCD1 whole-gene deletion was diagnosed with active cerebral adrenoleukodystrophy characterized by demyelination and gadolinium enhancement on brain MRI. He underwent hematopoietic cell transplant (HCT) with autologous CD34+ cells transduced with an ABCD1-expressing lentiviral vector (eli-cel [elivaldogene autotemcel]) as part of the ALD-104 clinical trial. Fifty days after HCT, the patient's MRI showed gadolinium resolution; the whole-blood vector copy number (VCN) was 0.666 copies/mL. Six months following HCT, an MRI showed re-emergence of gadolinium enhancement; the VCN had decreased to 0.029 copies/mL. Polyclonal antibodies to the ABCD1 gene product were detectable 9 months after transplant, showing reactivity to peroxisomes, suggesting an immune response; however, no antibody binding to human CD34+ cells could be shown. The patient underwent a successful allogeneic HCT 12 months after gene therapy with resultant gadolinium resolution, cerebral disease stabilization, and the disappearance of antibodies. The coincident VCN loss and appearance of antibody to the ABCD1 gene product is of interest, and we postulate that it is related to the patient's whole ABCD1 gene deletion. We suggest close monitoring of loss of gene therapy efficacy due to immune response in patients with full deletions who are considering gene therapy.

Effect of Age, Deboning Time of Carcass, and Different Cooking Conditions on the Woody Breast Myopathies in Chicken: A Meta-Analysis.

This meta-analysis review undertakes a comprehensive examination of various approaches for identifying myopathic fillets and meticulously evaluates the effects of bird age, deboning time, and different cooking and storage conditions on woody breast (WB) myopathic conditions in broiler deboned fillets. The data, meticulously collected from 20 articles based on predefined inclusion criteria sourced from various databases and online resources, reveal significant insights. For instance, the analysis uncovers that deboning time significantly affects Meullenet-Owens Razor Shear (MORS), Blunt Meullenet-Owens Razor Shear (BMORS), and descriptive analysis values (p < 0.001). Instrumentation techniques, such as compression force and shear force, along with different cooking conditions, strongly impact BMORS shear force values (R2 = 86.80%), with significance levels ranging from 0.01 to 0.001. Deboning time also substantially impacts MORS shear force values (R = 64.03%). In contrast, the effects of deboning time, bird age, and cooking conditions on descriptive sensory evaluation are minimal when compared to woody breast fillets (age of birds: R2 = 26.53%; cooking conditions: R2 = 32.57%; deboning time: R2 = 10.06%). The overall effect of bird age on chicken breast meat quality shows significant differences for the evaluated parameters (Hedges' g [95% CI] = -0.72 [0.17, 1.26], I2 = 93%, p < 0.01). The sous vide cooking method significantly affects shear force energies and sensory descriptive evaluation for woody breast fillets (Hedges' g [95% CI] = 5.30 [-50.30, 83.40], I2 = 98%, p < 0.01). These findings, with their significant implications, provide valuable insights for optimizing processing conditions in the poultry industry to reduce woody breast occurrences and enhance meat quality, instilling confidence in the robustness of the research.

Role of Noninvasive Urinary Prothrombin Fragment 1 + 2 to Measure Blood Coagulation Indices and Dose of Acenocoumarol.

PF1 + 2 plasma levels are a crucial indicator for assessing anticoagulant action in individuals receiving anticoagulant treatment. Urine also has PF1 + 2 levels due to its molecular size. Hence, the present study aims to measure urinary prothrombin fragment 1 + 2 (uPF1 + 2) in patients taking anticoagulants in order to divulge a noninvasive surrogate marker of PT-INR of blood coagulopathy. A total of 205 people participated in the study: 104 patients on acenocoumarol (AC) and 101 healthy controls (HC). Clinical parameters, including PT-INR, urinary creatinine, etc., were measured in all subjects. To evaluate uPF1 + 2 in samples, MALDI-TOF-MS, Western blot analysis, and ELISA tests were used. The MALDI-TOF-MS results showed the presence of uPF1 + 2 in both AC and HC urine samples. The Western blot, ELISA experiment, and unpaired t test results displayed that the patients with AC had significantly increased levels of uPF1 + 2 compared to HC. A regression study showed a strong positive relation between blood-based PT-INR and uPF1 + 2. ROC validation also revealed the clinical efficacy of uPF1 + 2. For the goal to monitor anticoagulant medication, the present study highlights PF1 + 2, which describes the overall hemostatic capacity and might be utilized in addition to or instead of PT-INR.

Probing and gauging of D-Penicillamine xenobiotics in hepatic Wilson disease patients.

D-penicillamine (PA) is the primary chelator of choice to treat Wilson disease (WD). There are limitations in obtaining comprehensive data on PA metabolites in biological specimens by conventional approaches. Hence, the aim of the present was to identify the major hepatic PA metabolites and draw clear conclusions of the drug's xenobiotic in WD. Urine samples were collected from children with hepatic WD (n = 63, aged 14.8 ± 4 years) 5 h after PA administration (16.3 ± 3.8 mg/kg/day) and age-matched healthy volunteers comprised as controls (n = 30). High-resolution 800 MHz nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry was applied to reveal unambiguous appraisals of different excretory by-products of PA metabolism. Four new products comprising penicillamine disulphide (PD), penicillamine cysteine disulphide (PCD), S-methyl penicillamine (SMP), and N-acetyl penicillamine (NAP) of PA xenobiotic metabolites were identified using high-resolution NMR spectroscopy. Quantitative levels of PCD and SMP were approximately three-fold higher than those of PD and NAP, respectively. High-resolution NMR identifies the major PA metabolites with certainty. Reduction, sulfation, and methylation are the predominant pathways of PA metabolism. There is a potential application for assessing therapeutic monitoring of chelation in hepatic WD.

Advances in Nickel-Containing High-Entropy Alloys: From Fundamentals to Additive Manufacturing.

High-entropy alloys (HEAs) are recognized as a class of advanced materials with outstanding mechanical properties and corrosion resistance. Among these, nickel-based HEAs stand out for their impressive strength, ductility, and oxidation resistance. This review delves into the latest advancements in nickel-containing HEAs, covering their fundamental principles, alloy design strategies, and additive manufacturing techniques. We start by introducing HEAs and their unique properties, emphasizing the crucial role of nickel. This review examines the complex relationships between alloy composition, valence electron concentration (VEC), and the resulting crystal structures. This provides insights into design principles for achieving desired microstructures and mechanical properties. Additive manufacturing (AM) techniques like selective laser melting (SLM), electron beam melting (EBM), and laser metal deposition (LMD) are highlighted as powerful methods for fabricating intricate HEA components. The review addresses the challenges of AM processes, such as porosity, fusion defects, and anisotropic mechanical properties, and discusses strategies to mitigate these issues through process optimization and improved powder quality. The mechanical behavior of AM-processed nickel-based HEAs is thoroughly analyzed, focusing on compressive strength, hardness, and ductility. This review underscores the importance of microstructural features, including grain size, phase composition, and deformation mechanisms, in determining the mechanical performance of these alloys. Additionally, the influence of post-processing techniques, such as heat treatment and hot isostatic pressing (HIP) on enhancing mechanical properties is explored. This review also examines the oxidation behavior of nickel-containing HEAs, particularly the formation of protective oxide scales and their dependence on aluminum content. The interplay between composition, VEC, and oxidation resistance is discussed, offering valuable insights for designing corrosion resistant HEAs. Finally, this review outlines the potential applications of nickel-based HEAs in industries such as aerospace, automotive, and energy, and identifies future research directions to address challenges and fully realize the potential of these advanced materials.

Biosynthesis of silver nanoparticle from flower extract of Dillenia indica and its efficacy as antibacterial and antioxidant.

Dillenia indica is a medicinal tree of the Dilleniaceae and its flower extract was used for the synthesis of silver nanoparticle (AgNPs). The optimal conditions for AgNPs synthesis were as such: 2 mM AgNO3, pH 4.5 and 48-h reaction time. The characteristic band of AgNPs was observed at the wavelength of 435 nm by UV-visible spectroscopic study. Fourier-transform infrared (FTIR) analysis depicted the involvement of several functional groups of plant extracts in the synthesis of AgNPs. Nanoparticles were mostly spherical shaped and uniformly distributed, when observation was made by Transmission electron microscopy (TEM). Energy Dispersive X-Ray (EDX) showed absorption peak approximately at 3 keV thus confirmed the presence of silver metal in AgNP. X-ray diffraction (XRD) investigation and selected area electron diffraction (SAED) patterns showed the crystalline nature of the AgNPs. Dynamic light scattering (DLS) analysis exhibited average size of the nanoparticles as 50.17 nm with a polydispersity index (PDI) value of 0.298. The zeta potential of nanoparticles was observed as -24.9 mV. To assess antibacterial activity, both AgNPs alone or its combination with the antibiotic were tried against six pathogenic bacteria. The combination of AgNPs with antibiotic was maximum effective against Shigella boydii (16.07 ± 0.35) and Klebsiella pneumoniae (15.03 ± 0.20). AgNPs alone showed maximum inhibition for both Gram-positive bacteria: methicillin-resistant Staphylococcus aureus (19.97 ± 0.20 mm) and Enterococcus faecium (19.80 ± 0.15 mm). Maximum inhibition of Enterobactor cloacae and Pseudomonas aeruginosa was observed by antibiotic taken alone. Evaluation through 2,2-diphenyl-1-picrylhydrazyl (DPPH) and DNA nicking assays demonstrated the antioxidant capabilities of the nanoparticles.

An Innovative Approach for Precise Identification of the Lowest Unoccupied Molecular Orbital Using the Parametric Equation of Motion.

The lowest unoccupied molecular orbital (LUMO) plays a crucial role in quantum chemistry, but current quantum chemistry calculations fail to provide useful virtual orbitals, making it challenging to explore various processes such as photochemical reactions, electron attachment, reduction, or excitation processes. The LUMO obtained from the self-consistent field (SCF) solution can not be relied upon and needs to be identified as they are often present among the continuum states having almost similar energies. The nuclear charge stabilization method has been proven useful in identifying LUMO. Herein, we have proposed the application of parametric equations of motion (PEM) in conjunction with nuclear charge stabilization method to identify the LUMO obtained from the SCF solution exhibiting stability with different basis sets including diffuse functions.

Effect of laparoscopic cholecystectomy on 25-hydroxyvitamin D levels and bone mineral density in post menopausal women.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the gold standard management for benign gallbladder diseases. It has been observed that there is alteration in vitamin D levels and bone mineral density after cholecystectomy due to altered enterohepatic circulation. With increase in average age expectancy of the population, low levels of vitamin D levels and osteoporosis after cholecystectomies might cause increased health care burden. METHODS: A prospective observational study was planned between 1 January 2022 and 30 June 2023 in the Department of General Surgery at PGIMER Chandigarh, a tertiary care hospital in north India. One hundred and three post-menopausal women who underwent LC and met the inclusion and exclusion criteria were included in the study. All participants underwent estimation of vitamin D and bone mineral density preoperatively and third-post operative month (POM). RESULTS: The mean age of the patients was 58.46 ± 7.44. Pain abdomen was present in 68(66%) patients, 18 had epigastric discomfort and 17 had dyspepsia. The mean levels of vitamin D decreased from 21.92 at the baseline to 20.12 at third POM (p < .001). There was a significant change in t score Femoral Neck (-1.12 vs -1.15, p < .001) and Lumbar spine L1-L4 - 1.98 vs -1.98 (p = .033). z-scores of the femoral neck were -0.34 vs -0.54 (p < .001) and of lumbar spine L1-L4 were -0.95 vs 1.02 (p < .001). The decrease in fracture risk for the femoral neck (p = .344) and the lumbar spine (p = .223) was not statistically significant. CONCLUSION: There is a significant decrease in vitamin D and BMD levels after LC in post-menopausal females.

Nanoscale core-shell structure and recrystallization of swift heavy ion tracks in SrTiO3.

It is widely accepted that the interaction of swift heavy ions with many complex oxides is predominantly governed by the electronic energy loss that gives rise to nanoscale amorphous ion tracks along the penetration direction. The question of how electronic excitation and electron-phonon coupling affect the atomic system through defect production, recrystallization, and strain effects has not yet been fully clarified. To advance the knowledge of the atomic structure of ion tracks, we irradiated single crystalline SrTiO3 with 629 MeV Xe ions and performed comprehensive electron microscopy investigations complemented by molecular dynamics simulations. This study shows discontinuous ion-track formation along the ion penetration path, comprising an amorphous core and a surrounding few monolayer thick shell of strained/defective crystalline SrTiO3. Using machine-learning-aided analysis of atomic-scale images, we demonstrate the presence of 4-8% strain in the disordered region interfacing with the amorphous core in the initially formed ion tracks. Under constant exposure of the electron beam during imaging, the amorphous part of the ion tracks readily recrystallizes radially inwards from the crystalline-amorphous interface under the constant electron-beam irradiation during the imaging. Cation strain in the amorphous region is observed to be significantly recovered, while the oxygen sublattice remains strained even under the electron irradiation due to the present oxygen vacancies. The molecular dynamics simulations support this observation and suggest that local transient heating and annealing facilitate recrystallization process of the amorphous phase and drive Sr and Ti sublattices to rearrange. In contrast, the annealing of O atoms is difficult, thus leaving a remnant of oxygen vacancies and strain even after recrystallization. This work provides insights for creating and transforming novel interfaces and nanostructures for future functional applications.

Unveiling perceptions regarding post mastectomy breast reconstruction: A questionnaire-based survey of patients from central India.

INTRODUCTION: Post mastectomy breast reconstruction uptake remains low in the developing countries. We examined patient perspectives about it in a cohort of Indian breast cancer patients. METHODS: This prospective study was conducted at a tertiary care center in central India. All post mastectomy patients for breast cancer were interviewed via a survey questionnaire to assess their perspective regarding post mastectomy breast reconstruction. RESULTS: None of the 192 patients underwent immediate or delayed reconstruction by the end of 24 months follow-up. Age, education level, occupation and marital status did not affect the uptake of post mastectomy breast reconstruction. The most common patient-reported reasons for not having reconstruction were the desire to avoid additional surgery and the belief that it was not important (80% for each). System related factors such as additional cost of surgery and additional length of stay were reported to be important by 55% and 65% patients respectively. CONCLUSION: Our survey of 192 post mastectomy breast cancer patients showed that none opted for post mastectomy reconstruction, suggesting significant barriers to it. Understanding and addressing these barriers are crucial to ensuring comprehensive care for these breast cancer patients.

International Society for Cell & Gene Therapy Stem Cell Engineering Committee report on the current state of hematopoietic stem and progenitor cell-based genomic therapies and the challenges faced.

Genetic manipulation of hematopoietic stem cells (HSCs) is being developed as a therapeutic strategy for several inherited disorders. This field is rapidly evolving with several novel tools and techniques being employed to achieve desired genetic changes. While commercial products are now available for sickle cell disease, transfusion-dependent ß-thalassemia, metachromatic leukodystrophy and adrenoleukodystrophy, several challenges remain in patient selection, HSC mobilization and collection, genetic manipulation of stem cells, conditioning, hematologic recovery and post-transplant complications, financial issues, equity of access and institutional and global preparedness. In this report, we explore the current state of development of these therapies and provide a comprehensive assessment of the challenges these therapies face as well as potential solutions.

Developmental delay can precede neurologic regression in early onset metachromatic leukodystrophy.

OBJECTIVE: Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disorder. Emerging therapies are most effective in the presymptomatic phase, and thus defining this window is critical. We hypothesize that early development delay may precede developmental plateau. With the advent of presymptomatic screening platforms and transformative therapies, it is essential to define the onset of neurologic disease. METHODS: The specific ages of gain and loss of developmental milestones were captured from the medical records of individuals affected by MLD. Milestone acquisition was characterized as: on target (obtained before the age limit of 90th percentile plus 2 standard deviations compared to a normative dataset), delayed (obtained after 90th percentile plus 2 standard deviations), or plateau (skills never gained). Regression was defined as the age at which skills were lost. LI-MLD was defined by age at onset before 2.5 years. RESULTS: Across an international cohort, 351 subjects were included (n = 194 LI-MLD subcohort). The median age at presentation of the LI-MLD cohort was 1.4 years (25th-75th %ile: 1.0-1.5). Within the LI-MLD cohort, 75/194 (39%) had developmental delay (or plateau) prior to MLD clinical presentation. Among the LI-MLD cohort with a minimum of 1.5 years of follow-up (n = 187), 73 (39.0%) subjects never attained independent ambulation. Within LI-MLD + delay subcohort, the median time between first missed milestone target to MLD decline was 0.60 years (maximum distance from delay to onset: 1.9 years). INTERPRETATION: Early developmental delay precedes regression in a subset of children affected by LI-MLD, defining the onset of neurologic dysfunction earlier than previously appreciated. The use of realworld data prior to diagnosis revealed an early deviation from typical development. Close monitoring for early developmental delay in presymptomatic individuals may help in earlier diagnosis with important consequences for treatment decisions.

Comprehensive review of deep learning in orthopaedics: Applications, challenges, trustworthiness, and fusion.

Deep learning (DL) in orthopaedics has gained significant attention in recent years. Previous studies have shown that DL can be applied to a wide variety of orthopaedic tasks, including fracture detection, bone tumour diagnosis, implant recognition, and evaluation of osteoarthritis severity. The utilisation of DL is expected to increase, owing to its ability to present accurate diagnoses more efficiently than traditional methods in many scenarios. This reduces the time and cost of diagnosis for patients and orthopaedic surgeons. To our knowledge, no exclusive study has comprehensively reviewed all aspects of DL currently used in orthopaedic practice. This review addresses this knowledge gap using articles from Science Direct, Scopus, IEEE Xplore, and Web of Science between 2017 and 2023. The authors begin with the motivation for using DL in orthopaedics, including its ability to enhance diagnosis and treatment planning. The review then covers various applications of DL in orthopaedics, including fracture detection, detection of supraspinatus tears using MRI, osteoarthritis, prediction of types of arthroplasty implants, bone age assessment, and detection of joint-specific soft tissue disease. We also examine the challenges for implementing DL in orthopaedics, including the scarcity of data to train DL and the lack of interpretability, as well as possible solutions to these common pitfalls. Our work highlights the requirements to achieve trustworthiness in the outcomes generated by DL, including the need for accuracy, explainability, and fairness in the DL models. We pay particular attention to fusion techniques as one of the ways to increase trustworthiness, which have also been used to address the common multimodality in orthopaedics. Finally, we have reviewed the approval requirements set forth by the US Food and Drug Administration to enable the use of DL applications. As such, we aim to have this review function as a guide for researchers to develop a reliable DL application for orthopaedic tasks from scratch for use in the market.

Quality Improvement in Neonatal Care: Successful Adoption of the Eat, Sleep, Console Protocol in a Rural Hospital Setting.

Introduction: The United States faces a growing burden of neonatal opioid withdrawal syndrome in rural hospitals. Traditional treatments often extend hospital stays and medication use. The Eat, Sleep, and Console (ESC) approach offers a new management strategy but is challenging in resource-limited settings. This study aimed to apply ESC in rural hospitals to reduce neonatal intensive care unit admissions, decrease length of stay (LOS) to under 7 days, and lower medication use by more than 80% within a year. Methods: Our quality improvement initiative at rural hospitals implemented a multimodal approach for in utero opioid-exposed infants, involving staff education, electronic medical record updates, and nonpharmacological care strategies. Data from January 2020 to December 2023 assessed treatment impact, including pharmacotherapy need and hospital stay lengths, using statistical process control for analysis. Results: After ESC implementation, the percentage of opioid-exposed infants receiving pharmacological treatment significantly decreased from 60.7% to 7.9%. The average LOS was reduced from 14.5 days to 5.25 days. These improvements persisted for 24 months, with no readmissions within 30 days of discharge. This approach also reduced hospital charges by over $5 million, demonstrating its clinical and financial effectiveness. Conclusions: The multidisciplinary approach successfully implemented ESC in a resource-limited setting, significantly reducing both the LOS and medication exposure for opioid-exposed infants while also saving significant healthcare costs. This successful model has been adopted by at least four regional rural hospitals, thus broadening the program's impact.

Nanoparticles as a Tool for Alleviating Plant Stress: Mechanisms, Implications, and Challenges.

Plants, being sessile, are continuously exposed to varietal environmental stressors, which consequently induce various bio-physiological changes in plants that hinder their growth and development. Oxidative stress is one of the undesirable consequences in plants triggered due to imbalance in their antioxidant defense system. Biochemical studies suggest that nanoparticles are known to affect the antioxidant system, photosynthesis, and DNA expression in plants. In addition, they are known to boost the capacity of antioxidant systems, thereby contributing to the tolerance of plants to oxidative stress. This review study attempts to present the overview of the role of nanoparticles in plant growth and development, especially emphasizing their role as antioxidants. Furthermore, the review delves into the intricate connections between nanoparticles and plant signaling pathways, highlighting their influence on gene expression and stress-responsive mechanisms. Finally, the implications of nanoparticle-assisted antioxidant strategies in sustainable agriculture, considering their potential to enhance crop yield, stress tolerance, and overall plant resilience, are discussed.

Efficacy of the omental roll-up technique in pancreaticojejunostomy to prevent postoperative pancreatic fistula after pancreaticoduodenectomy.

Backgrounds/Aims: Pancreaticoduodenectomy (PD) is being performed more frequently. A pancreaticojejunostomy (PJ) leak is the major determinant of patient outcomes. An omental flap around PJ might improve postoperative outcomes. Methods: A prospective randomized controlled trial was planned at PGIMER, Chandigarh. Fifty-eight patients meeting the criteria were included in the study. Group A underwent PD with omental roll-up and group B underwent standard PD. Results: The mean age of patients in group A was 57.1 ± 14.3 years and 51.2 ± 10.7 in group B. Jaundice (p = 0.667), abdominal pain (p = 0.69), and co-morbidities were equal among the groups. The body mass index of patients in group B was higher at 24.3 ± 5.4 kg/m2 (p = 0.03). The common bile duct diameter (12.6 ± 5.3 mm vs. 17.2 ± 10.3 mm, p = 0.13) and the pancreatic duct diameter (4.06 ± 2.01 mm vs. 4.60 ± 2.43 mm, p = 0.91) were comparable. The intraoperative blood loss (mL) was significantly higher in group B (233.33 ± 9.57 vs. 343.33 ± 177.14, p = 0.04). Drain fluid amylase levels on postoperative day (POD) 1 (p = 0.97) and POD3 (p = 0.92) were comparable. The rate of postoperative pancreatic fistula (POPF) grade A (p ≥ 0.99) and grade B (p = 0.54) were comparable. The mean postoperative length of stay among was similar (p = 0.89). Conclusions: An omental wrap can be performed without increase in complexity of the procedure. However, its utility in preventing POPFs and morbidity remains unclear.

Medial scapular body (MSB) Goutallier classification: MRI-based reliability and validity of evaluation of the Goutallier classification for grading fatty infiltration of the rotator cuff.

BACKGROUND: The degree of atrophy and fatty infiltration of rotator cuff muscle belly is a key predictor for cuff repairability. Traditionally, Goutallier grading of fatty infiltration is assessed at sagittal scapular Y-view. Massive rotator cuff tears are associated with tendon retraction and medial retraction of cuff musculature, resulting in medialization of the muscle bulk. Thus, standard Y-view can misrepresent the region of interest and may misguide clinicians when assessing repairability. It is hypothesized that by assessing the muscle belly with multiple medial sagittal magnetic resonance imaging (MRI) sections at the medial scapular body, the Medial Scapular Body-Goutallier Classification (MSB-GC) will improve reliability and repeatability, giving a more representative approximation to the degree of fatty infiltration, as compared with the original Y-view. METHODS: Fatty infiltration of the rotator cuff muscles were classified based on the Goutallier grade (0-4) at 3 defined sections: section 1, original Y-view; section 2, level of suprascapular notch; and section 3, 3 cm medial to the suprascapular notch on MRI scans. Six subspecialist fellowship-trained shoulder surgeons and 3 musculoskeletal radiologists independently evaluated deidentified MRI scans of included patients. RESULTS: Of 80 scans, 78% (n = 62) were massive cuff tears involving the supraspinatus, infraspinatus, and subscapularis tendons. Interobserver reliability (consistency between observers) for Goutallier grade was excellent for all 3 predefined sections (range: 0.87-0.95). Intraobserver reliability (repeatability) for Goutallier grade was excellent for all 3 sections and 4 rotator cuff muscles (range: 0.83-0.97). There was a moderate to strong positive correlation of Goutallier grades between sections 1 and 3 and between sections 2 and 3 and these were statistically significant (P < .001). There was a reduction in the severity of fatty infiltration on the Goutallier classification from sections 1 to 3 across all muscles: 42.5% of both supraspinatus and infraspinatus were downgraded by 1, 20% of supraspinatus and 3.8% of infraspinatus were downgraded by 2, and 2.5% of supraspinatus were downgraded by 3. CONCLUSION: This study found that applying the Goutallier classification to more medial MRI sections (MSB-GC) resulted in assignment of lower grades for all rotator cuff muscles. Additionally, this method demonstrated excellent test-retest reliability and repeatability. Inclusion of a more medial view or whole scapula on MRI, especially in advanced levels of tear retraction, could be more reliable and representative for assessment of the degree of fatty infiltration within the muscle bulk that could help predict tear repairability and therefore improve clinical decision making, which should be studied further in clinical studies.