Identification of potent BRD4-BD1 inhibitors using classical and steered molecular dynamics based free energy analysis.

In the present work a combination of traditional and steered molecular dynamics based techniques were employed to identify potential inhibitors against the human BRD4 protein (BRD4- BD1); an established drug target for multiple illnesses including various malignancies. Quinoline derivatives that were synthesized in-house were tested for their potential as new BRD4-BD1 inhibitors. Initially molecular docking experiments were performed to determine the binding poses of BRD4-BD1 inhibitors. To learn more about the thermodynamics of inhibitor binding to the BRD4-BD1 active site, the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) free energy calculations were conducted afterwards. The findings of the MM-PBSA analysis were further reinforced by performing steered umbrella sampling simulations which revealed crucial details about the binding/unbinding process of the most potent quinoline derivatives at the BRD4-BD1 active site. We report a novel quinoline derivative which can be developed into a fully functional BRD4-BD1 inhibitor after experimental validation. The identified compound (4 g) shows better properties than the standard BRD4-BD1 inhibitors considered in the study. The study also highlights the crucial role of Gln78, Phe79, Trp81, Pro82, Phe83, Gln84, Gln85, Val87, Leu92, Leu94, Tyr97, Met105, Cys136, Asn140, Ile146 and Met149 in inhibitor binding. The study provides a possible lead candidate and key amino acids involved in inhibitor recognition and binding at the active site of BRD4-BD1 protein. The findings might be of significance to medicinal chemists involved in the development of potent BRD4-BD1 inhibitors.

Impact of environmental temperature on the survival outcomes of breast cancer: A SEER-based study.

BACKGROUND: Experimental evidence in tumor-bearing mouse models shows that exposure to cool, that is, sub-thermoneutral environmental temperature is associated with a higher tumor growth rate and an immunosuppressive tumor immune microenvironment than seen at thermoneutral temperatures. However, the translational significance of these findings in humans is unclear. We hypothesized that breast cancer patients living in warmer climates will have better survival outcomes than patients living in colder climates. METHODS: A retrospective population-based analysis was conducted on 270,496 stage I-III breast cancer patients, who were retrieved from the Surveillance, Epidemiology and End Results (SEER) over the period from 1996 to 2017. The average annual temperature (AAT) was calculated based on city level data from the National Centers for Environmental Information. RESULTS: A total of 270, 496 patients were analyzed. Temperature as assessed in quartiles. After adjusting for potential confounders, patients who lived in the 3rd and 4th quartile temperature regions with AAT 56.7-62.5°F (3rd quartile) and > 62.5°F (4th quartile) had a 7% increase in the OS compared to patients living at AAT < 48.5°F (1st quartile) (HR 0.93, 95% CI 0.90-0.95 and HR 0.93, 95% CI 0.91-0.96, respectively). For DSS, When comparing AAT quartiles, patients living with AAT in the range of 56.7-62.5°F and > 62.5°F demonstrated a 7% increase each in DSS after adjustment (HR 0.93, 95% CI 0.90-0.96 and HR 0.93, 95% CI 0.90-0.96). CONCLUSIONS: Higher environmental temperatures are associated with significantly better OS and DSS in breast cancer patients. Future research is warranted to confirm this observation using large datasets to elucidate the underlying mechanisms and investigate novel therapeutic strategies to minimize this geographic disparity in clinical outcomes.

Creation of Multi-Principal Element Alloy NiCoCr Nanostructures via Nanosecond Laser-Induced Dewetting.

The multi-principal element alloy nanoparticles (MPEA NPs), a new class of nanomaterials, present a highly rewarding opportunity to explore new or vastly different functional properties than the traditional mono/bi/multimetallic nanostructures due to their unique characteristics of atomic-level homogeneous mixing of constituent elements in the nanoconfinements. Here, the successful creation of NiCoCr nanoparticles, a well-known MPEA system is reported, using ultrafast nanosecond laser-induced dewetting of alloy thin films. Nanoparticle formation occurs by spontaneously breaking the energetically unstable thin films in a melt state under laser-induced hydrodynamic instability and subsequently accumulating in a droplet shape via surface energy minimization. While NiCoCr alloy shows a stark contrast in physical properties compared to individual metallic constituents, i.e., Ni, Co, and Cr, yet the transient nature of the laser-driven process facilitates a homogeneous distribution of the constituents (Ni, Co, and Cr) in the nanoparticles. Using high-resolution chemical analysis and scanning nanodiffraction, the environmental stability and grain arrangement in the nanoparticles are further investigated. Thermal transport simulations reveal that the ultrashort (≈100 ns) melt-state lifetime of NiCoCr during the dewetting event helps retain the constituent elements in a single-phase solid solution with homogenous distribution and opens the pathway to create the unique MPEA nanoparticles with laser-induced dewetting process.

Application Scopes of Miniaturized MXene-Functionalized Electrospun Nanofibers-Based Electrochemical Energy Devices.

Exploring combinatorial materials, as well as rational device configuration design, are assumed to be the key strategies for deploying versatile electrochemical devices. MXene sheets have revealed a high hydrophilic surface with proper mechanical and electrical characteristics, rendering them supreme additive candidates to integrate in electrospun electrochemical power tools. The synergetic effects of MXene 2D layers with the nanofibrous networks can boost actuator responsive ability, battery capacity retention, fuel cell stability, sensor sensitivity, and supercapacitor areal capacitance. Their superior mechanical features can be endowed to the electrospun layers through the embedding of the MXene additive. In this review, the preparation and inherent features of the MXene configurations are briefly evaluated. The fabrication and overall performance of the MXene-loaded nanofibers applicable in electrochemical actuators, batteries, fuel cells, sensors, and supercapacitors are comprehensively figured out. Eventually, an outlook on the future development of MXene-based electrospun composites is presented. A substantial focus has been devoted to date to engineering conjugated MXene and electrospun fibrous frames. The potential performance of the MXene-decorated nanofibers presents a bright future of nanoengineering toward technological growth. Meanwhile, a balance between the pros and cons of the synthesized MXene composite layers is worthwhile to consider in the future.

Hurler Syndrome Glycosaminoglycans Decrease in Cerebrospinal Fluid without Brain-Targeted Therapy.

Novel therapies for Hurler syndrome aim to cross the blood-brain barrier (BBB) to target neurodegeneration by degrading glycosaminoglycans (GAG). BBB penetration has been assumed with decreased cerebrospinal fluid (CSF) GAG, yet little is known about CSF GAG without brain-targeting therapies. We compared pre-transplant CSF GAG in patients who were treatment naïve (n = 19) versus receiving standard non-BBB penetrating enzyme replacement therapy (ERT, n = 12). In the ERT versus treatment naïve groups, CSF GAG was significantly lower across all content assayed, raising questions about using CSF GAG decrements to show BBB penetration. Future studies should compare GAG reduction in standard versus novel therapies. ANN NEUROL 2023;94:1182-1186.

Mitochondrial Creatine Kinase Attenuates Pathologic Remodeling in Heart Failure.

BACKGROUND: Abnormalities in cardiac energy metabolism occur in heart failure (HF) and contribute to contractile dysfunction, but their role, if any, in HF-related pathologic remodeling is much less established. CK (creatine kinase), the primary muscle energy reserve reaction which rapidly provides ATP at the myofibrils and regenerates mitochondrial ADP, is down-regulated in experimental and human HF. We tested the hypotheses that pathologic remodeling in human HF is related to impaired cardiac CK energy metabolism and that rescuing CK attenuates maladaptive hypertrophy in experimental HF. METHODS: First, in 27 HF patients and 14 healthy subjects, we measured cardiac energetics and left ventricular remodeling using noninvasive magnetic resonance 31P spectroscopy and magnetic resonance imaging, respectively. Second, we tested the impact of metabolic rescue with cardiac-specific overexpression of either Ckmyofib (myofibrillar CK) or Ckmito (mitochondrial CK) on HF-related maladaptive hypertrophy in mice. RESULTS: In people, pathologic left ventricular hypertrophy and dilatation correlate closely with reduced myocardial ATP levels and rates of ATP synthesis through CK. In mice, transverse aortic constriction-induced left ventricular hypertrophy and dilatation are attenuated by overexpression of CKmito, but not by overexpression of CKmyofib. CKmito overexpression also attenuates hypertrophy after chronic isoproterenol stimulation. CKmito lowers mitochondrial reactive oxygen species, tissue reactive oxygen species levels, and upregulates antioxidants and their promoters. When the CK capacity of CKmito-overexpressing mice is limited by creatine substrate depletion, the protection against pathologic remodeling is lost, suggesting the ADP regenerating capacity of the CKmito reaction rather than CK protein per se is critical in limiting adverse HF remodeling. CONCLUSIONS: In the failing human heart, pathologic hypertrophy and adverse remodeling are closely related to deficits in ATP levels and in the CK energy reserve reaction. CKmito, sitting at the intersection of cardiac energetics and redox balance, plays a crucial role in attenuating pathologic remodeling in HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00181259.

All-Arthroscopic Supraspinatus and Infraspinatus Muscle Advancement Leads to High Healing Rate and Excellent Outcomes in Patients With Massive, Retracted Rotator Cuff Tears, Even in Patients With Pseudoparalysis.

PURPOSE: To evaluate the clinical and radiographic outcomes of an all-arthroscopic rotator cuff repair technique involving muscle advancement and double-layer lasso loop (DLLL) repair for massive, retracted posterosuperior cuff tears. METHODS: This was a retrospective case series of patients with massive, retracted posterosuperior cuff tears who underwent the all-arthroscopic muscle advancement technique from March 2017 to September 2021, with a minimum follow-up of 12 months. Key steps included suprascapular nerve release, advancement of the supraspinatus and infraspinatus muscles, and DLLL repair. Preoperative and postoperative visual analog scale score for pain, American Shoulder and Elbow Surgeons (ASES) shoulder score, Constant score, University of California, Los Angeles (UCLA) shoulder score, active range of motion, and strength were compared. Preoperative and postoperative structural radiologic characteristics were analyzed. RESULTS: We evaluated 43 shoulders in 38 patients with a mean follow-up period of 18.8 months (range, 12-55 months). Of the 43 shoulders, 4 showed repair failure (9.3% retear rate). Visual analog scale, ASES, Constant, and UCLA scores significantly improved (P < .001) in patients who showed healing on postoperative magnetic resonance imaging (n = 39). ASES, Constant, and UCLA scores were significantly better in the healed group, with 100% exceeding the minimal clinically important difference for the ASES score and UCLA score and 84.2%, for Constant score. A lower proportion of patients in the retear group achieved the minimal clinically important difference. Active range of motion in all planes significantly improved for patients who had healed repairs (P < .001). Relative abduction strength, supraspinatus strength, and infraspinatus strength were at least 90% of those on the contralateral side. The recovery rate of pseudoparalysis (7 patients) was 100%. CONCLUSIONS: All-arthroscopic muscle advancement, coupled with DLLL repair, leads to a high healing rate with excellent clinical outcomes and recovery of strength to at least 90%, even in patients with pseudoparalysis. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Does forearm referencing using a retroversion guide achieve the targeted retroversion of the humeral component in reverse shoulder arthroplasty?

BACKGROUND: Component positioning affects clinical outcomes of reverse shoulder arthroplasty, which necessitates an implantation technique that is reproducible, consistent, and reliable. This study aims to assess the accuracy and precision of positioning the humeral component in planned retroversion using a forearm referencing guide. METHODS: Computed tomography scans of 54 patients (27 males and 27 females) who underwent primary reverse shoulder arthroplasty for osteoarthritis or cuff tear arthropathy were evaluated. A standardized surgical technique was used to place the humeral stem in 15° of retroversion. Version was assessed intraoperatively visualizing the retroversion guide from above and referencing the forearm axis. Metal subtraction techniques from postoperative computed tomography images allowed for the generation of 3D models of the humerus and for evaluation of the humeral component position. Anatomical humeral plane and implant planes were defined and the retroversion 3D angle between identified planes was recorded for each patient. Accuracy and precision were assessed. A subgroup analysis evaluated differences between male and female patients. RESULTS: The humeral retroversion angle ranged from 0.9° to 22.8°. The majority (81%) of the measurements were less than 15°. Mean retroversion angle (±SD) was 9.9° ± 5.8° (95% CI 8.4°-11.5°) with a mean percent error with respect to 15° of -34% ± 38 (95% CI -23 to -44). In the male subgroup (n = 27, range 3.8°-22.5°), the mean retroversion angle was 11.9° ± 5.4° (95% CI 9.8°-14.1°) with a mean percent error with respect to 15° of -21% ± 36 (95% CI -6 to -35). In the female subgroup (n = 27, range 0.9°-22.8°), mean retroversion angle was 8.0° ± 5.5° (95% CI 5.8°-10.1°) and the mean percent error with respect to 15° was -47% ± 36 (95% CI -32 to -61). The differences between the 2 gender groups were statistically significant (P = .006). CONCLUSION: Referencing the forearm using an extramedullary forearm referencing system to position the humeral stem in a desired retroversion is neither accurate nor precise. There is a nonnegligible tendency to achieve a lower retroversion than planned, and the error is more marked in females.

Comparison of Shoulder Range of Motion Quantified with Mobile Phone Video-Based Skeletal Tracking and 3D Motion Capture-Preliminary Study.

BACKGROUND: The accuracy of human pose tracking using smartphone camera (2D-pose) to quantify shoulder range of motion (RoM) is not determined. METHODS: Twenty healthy individuals were recruited and performed shoulder abduction, adduction, flexion, or extension, captured simultaneously using a smartphone-based human pose estimation algorithm (Apple's vision framework) and using a skin marker-based 3D motion capture system. Validity was assessed by comparing the 2D-pose outcomes against a well-established 3D motion capture protocol. In addition, the impact of iPhone positioning was investigated using three smartphones in multiple vertical and horizontal positions. The relationship and validity were analysed using linear mixed models and Bland-Altman analysis. RESULTS: We found that 2D-pose-based shoulder RoM was consistent with 3D motion capture (linear mixed model: R2 > 0.93) but was somewhat overestimated by the smartphone. Differences were dependent on shoulder movement type and RoM amplitude, with adduction the worst performer among all tested movements. All motion types were described using linear equations. Correction methods are provided to correct potential out-of-plane shoulder movements. CONCLUSIONS: Shoulder RoM estimated using a smartphone camera is consistent with 3D motion-capture-derived RoM; however, differences between the systems were observed and are likely explained by differences in thoracic frame definitions.

TIP60 acts as a regulator of genes involved in filopodia formation and cell migration during wound healing.

Wound healing is a complex phenomenon that requires coordination of numerous molecular and cellular changes to facilitate timely and efficient repair of the damaged tissue. Although many of these molecular pathways have been detailed, others remain to be elucidated. In the present work, we show for the first time, roles for the acetyltransferase TIP60 and nuclear receptor transcription factor PXR in this process, participating in wound healing by altering actin dynamics and cellular motility. We found that in response to wound-injury, TIP60 induces rapid formation of filopodia at the wounded cell front, leading to enhanced cell migration and faster closure of the wound. Further, qPCR analysis revealed heightened expression of Cdc42 and ROCK1 genes, key regulators involved in filopodia formation and actin reorganization, exclusively in TIP60-PXR-expressing cells upon wound-induction. We also performed ChIP assays to confirm the context-specific binding of TIP60 on the ROCK1 promoter and demonstrated that the TIP60 chromodomain is essential for loading of the TIP60-PXR complex onto the chromatin. Results from immunoprecipitation assays revealed that during the wounded condition, TIP60 alters the chromatin microenvironment by specifically acetylating histones H2B and H4, thereby modulating the expression of target genes. Overall, findings of this study show that TIP60 is a novel regulator of the wound healing process by regulating the expression of wound repair-related genes.

Evaluation of prostate cancer tissue metabolomics: would clinics utilise it for diagnosis?

The difficulty of diagnosing prostate cancer (PC) with the available biomarkers frequently leads to over-diagnosis and overtreatment of PC, underscoring the need for novel molecular signatures. The purpose of this review is to provide a summary of the currently available cellular metabolomics for PC molecular signatures. A comprehensive search on PubMed was conducted to find studies published between January 2004 and August 2022 that reported biomarkers for PC detection, development, aggressiveness, recurrence and treatment response. Although potential studies have reported the presence of distinguishing molecules that can distinguish between benign and cancerous prostate tissue. However, there are few studies looking into signature molecules linked to disease development, therapy response or tumour recurrence. The majority of these studies use high-dimensional datasets, and the number of potential metabolites investigated frequently exceeds the size of the available samples. In light of this, pre-analytical, statistical, methodological and confounding factors such as antiandrogen therapy (NAT) may also be linked to the identified chemometric multivariate differences between PC and relevant control samples in the datasets. Despite the methodological and procedural challenges, a range of methodological groups and processes have consistently identified a number of signature metabolites and pathways that appear to imply a substantial involvement in the cellular metabolomics of PC for tumour formation and recurrence.

Hematopoietic cell transplantation for Mucopolysaccharidosis I in the presence of decreased cardiac function.

BACKGROUND: Severe mucopolysaccharidosis type I, (MPS IH) is a rare inherited lysosomal disorder resulting in progressive storage of proteoglycans (GAGs) in central nervous system and somatic tissues and, if left untreated, causing death within the first decade of life. Hematopoietic cell transplantation (HCT) arrests many of the features of MPS IH but carries a 10-15% risk of mortality. Decreased cardiac function can occur in MPS IH and increase the risk of HCT. METHODS: Retrospective chart review was performed to determine the long-term outcome of individuals evaluated for HCT with MPS IH who had decreased cardiac function as measured by cardiac echocardiogram (echo) and ejection fraction (EF) of <50% at the time of initial evaluation. RESULTS: Six patients ranging in age from 1 week to 21 months (median: 4 months) had EFs ranging from 25 to 47% (median: 32%) at diagnosis and were initiated on enzyme replacement therapy (ERT) with improvement in EF in three patients by 5 months. The remaining three patients continued to have EFs <50% and continuous milrinone infusion was added in the pre-HCT period. On average, milrinone infusion was able to be discontinued post-HCT, prior to hospital discharge, within a mean of 37 days. Five patients survived HCT and are alive today with normal EFs. One patient receiving milrinone died of sepsis during HCT with a normal EF. CONCLUSION: Decreased cardiac systolic function in infants with MPS IH that fails to normalize with ERT alone may benefit from the addition of continuous milrinone infusion during HCT.

Cardiac 31P MR spectroscopy: development of the past five decades and future vision-will it be of diagnostic use in clinics?

In the past five decades, the use of the magnetic resonance (MR) technique for cardiovascular diseases has engendered much attention and raised the opportunity that the technique could be useful for clinical applications. MR has two arrows in its quiver: One is magnetic resonance imaging (MRI), and the other is magnetic resonance spectroscopy (MRS). Non-invasively, highly advanced MRI provides unique and profound information about the anatomical changes of the heart. Excellently developed MRS provides irreplaceable and insightful evidence of the real-time biochemistry of cardiac metabolism of underpinning diseases. Compared to MRI, which has already been successfully applied in routine clinical practice, MRS still has a long way to travel to be incorporated into routine diagnostics. Considering the exceptional potential of 31P MRS to measure the real-time metabolic changes of energetic molecules qualitatively and quantitatively, how far its powerful technique should be waited before a successful transition from "bench-to-bedside" is enticing. The present review highlights the seminal studies on the chronological development of cardiac 31P MRS in the past five decades and the future vision and challenges to incorporating it for routine diagnostics of cardiovascular disease.

Characterization of primary hyperparathyroidism based on target organ involvement: An analysis from the Indian PHPT registry.

BACKGROUND: It has been a matter of debate for long time about the existence of two distinct phenotypes of primary hyperparathyroidism (PHPT) predisposed to either renal or skeletal manifestation. OBJECTIVE: To differentiate characteristics of symptomatic PHPT patients based on the presence of skeletal or renal involvement. DESIGN: Retrospective analysis of data from the Indian PHPT registry. PATIENTS: PHPT patients were divided into four discrete groups: asymptomatic, presenting with renal manifestations alone, skeletal manifestations alone, and both skeletal and renal manifestations. MEASUREMENTS: Clinical, biochemical, and tumour weight and histopathological characteristics of these groups were compared. RESULTS: Of the 229 eligible patients, 45 were asymptomatic, 62 had renal manifestations, 55 had skeletal manifestations, and 67 had both skeletal and renal manifestations. Patients with both skeletal and renal manifestations had higher serum calcium levels than those with isolated skeletal involvement [12.5 (11.1-13.7) mg/dL, 11.2 (10.6-12.3) mg/dL, respectively; p < .05]. Serum alkaline phosphatase (AP), plasma parathyroid hormone (PTH) levels, and parathyroid tumour weight were significantly higher in patients with isolated skeletal, and both skeletal and renal manifestations, compared to the other two groups. A preoperative PTH and AP level of 300 pg/mL and 152 U/L, predicted the risk of developing skeletal involvement with sensitivity and specificity of 71%, 70%, and 69%, 67%, respectively. CONCLUSIONS: We observed distinct skeletal and renal phenotypic subgroups among PHPT patients with characteristic biochemical and hormonal patterns with higher parathyroid disease burden in patients with skeletal complications compared to those with isolated renal manifestation.

Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities.

Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.

Neurocognitive and mental health impact of adrenoleukodystrophy across the lifespan: Insights for the era of newborn screening.

X-linked adrenoleukodystrophy (ALD) is a rare inherited neurological disorder that poses considerable challenges for clinical management throughout the lifespan. Although males are generally more severely affected than females, the time course and presentation of clinical symptoms are otherwise difficult to predict. Opportunities to improve outcomes for individuals with ALD are rapidly expanding due to the introduction of newborn screening programs for this condition and an evolving treatment landscape. The aim of this comprehensive review is to synthesize current knowledge regarding the neurocognitive and mental health effects of ALD. This review provides investigators and clinicians with context to improve case conceptualization, inform prognostic counseling, and optimize neuropsychological and mental health care for patients and their families. Results highlight key predictive factors and brain-behavior relationships associated with the diverse manifestations of ALD. The review also discusses considerations for endpoints within clinical trials and identifies gaps to address in future research.

Enhanced electrical and magnetic functionality of Ni-Zn-co-doped CoFe2O4 rGO nanocomposites.

Enhancement in electrical and magnetic functionalities of rGO CoFe2O4 and Co0.7Zn0.3Fe1.7Ni0.3O4 nanocomposites was identified compared to their spinel-type metal oxides. Moreover, changes in morphology that occurred during the formation of the composites were fabricated via a simple in situ hydrothermal route. Electron microscopic investigations confirmed that the microspheres of the metal oxides were constructed by porous nanolamellae comprising nanoparticles interconnected to form highly stable porous microspheres. Conversely, in rGO-CoFe2O4 and rGO-Co0.7Zn0.3Fe1.7Ni0.3O4 composites, distorted spinel-type metal oxide spheres on rGO sheets were observed. Frequency-dependent conductivity increased with an increase in temperature, obeying Jonscher's power law and Koop's phenomenological theory. The resistance of ferrites decreased from ∼1.4 MΩ to 30 KΩ for their respective rGO-based nanocomposites. The hysteresis curves of all the compounds showed them to be isotropic, soft ferrimagnetic in nature. Furthermore, a 30-50% enhancement in the values of magnetic parameters of the ferrites occurred when they were interfaced with rGO sheets. This enhancement was probably due to the interfacial interaction of rGO with ferrites. Such enhancement may afford an advancement in the potential applications of these nanocomposites.

Exaggerated response to pattern reversal visual evoked potential among migraineurs.

OBJECTIVE: Visual evoked potential recording has reported ambiguous results among migraineurs, thus the present study explored the association of check-size and reversal rates on the latency and amplitude of pattern reversal VEP among migraineurs. METHOD AND MATERIAL: Monocular VEP responses for both eyes were recorded in 133 migraineurs and 111 controls. Checkerboard pattern with phase reversal frequency of 0.5, 1, 2 and 4 Hz and check-size of 16 × 16, 32 × 32, 64 × 64 and 128 × 128, i.e. spatial frequency of 0.475, 1.029, 2.056 and 4.112 cycle per degree (cpd) were used to record 100 responses each. Three-minutes gap was given after change of reversal frequency to a higher rate for next cycle of 4 check-size records. RESULT: A linear increase in latencies was observed with decreasing check-size in both groups, but migraineurs had significantly higher latencies at a given reversal rate. Amplitudes A1 and A2 were higher among migraineurs and amplitude A2 showed an inverted 'U' shaped trend with maximum amplitude at 32 × 32 check size (1.029 cpd) in both groups, with an exaggerated response among migraineurs. Check-size 32 × 32 i.e. spatial frequency of 1.029 behaves differently than other larger or smaller check-sizes. CONCLUSION: Variable VEP response for different visual stimuli may be due to differential activation of respective retinocortical pathways and cortical areas. The highest amplitude at modest check-size suggests a contributory role of foveal-parafoveal fibres in migraineurs. Exaggerated physiological response to visual stimuli may be responsible for higher amplitudes and prolonged latencies among migraineurs.

Exaggerated physiological VEP response as higher amplitudes and prolonged latencies, among migraineurs may be due to differential activation of respective retinocortical pathways and cortical areas.

Anterior deltoid muscle reflection using a deltopectoral approach is safe and does not influence outcome of reverse shoulder arthroplasty.

BACKGROUND: The deltopectoral approach is well accepted for shoulder arthroplasty procedures. The extended deltopectoral approach with detachment of the anterior deltoid from the clavicle allows increased joint exposure and can protect the anterior deltoid from traction injury. The efficacy of this extended approach has been demonstrated in anatomic total shoulder replacement surgery. However, this has not been shown in reverse shoulder arthroplasty (RSA). The primary aim of this study was to evaluate the safety of the extended deltopectoral approach in RSA. The secondary aim was to evaluate the performance of the deltoid reflection approach in terms of complications and surgical, functional, and radiologic outcomes up to 24 months after surgery. METHODS: A prospective, nonrandomized comparative study was performed between January 2012 and October 2020 including 77 patients in the deltoid reflection group and 73 patients in the comparative group. The decision for inclusion was based on patient and surgeon factors. Complications were recorded. Patients were followed up for ≥24 months to evaluate their shoulder function and undergo ultrasound evaluation. Functional outcome measures included the Oxford Shoulder Score, Disabilities of the Arm, Shoulder and Hand score, American Shoulder and Elbow Surgeons score, pain intensity (rated on visual analog scale [VAS] from 0 to 100), and range of motion (forward flexion, abduction, and external rotation). A regression analysis was performed to evaluate any factors of influence on the VAS score. RESULTS: There were no significant differences in the complication rate between the 2 groups (14.5% in deltoid reflection group and 13.8% in comparative group, P = .915). Ultrasound evaluation was available in 64 patients (83.1%), and no proximal detachment was observed. In addition, there were no significant differences in functional outcome measures both preoperatively and at 24 months after surgery between the groups assessed based on the mean VAS pain score, Oxford Shoulder Score, Disabilities of the Arm, Shoulder and Hand score, American Shoulder and Elbow Surgeons score, forward flexion, abduction, and external rotation. Adjustment for possible confounders in a regression model indicated that only prior surgery significantly influenced the VAS pain score after surgery (P = .031; 95% confidence interval, 0.574-11.67). Deltoid reflection (P = .068), age (P = .466), sex (P = .936), use of glenoid graft (P = .091), prosthesis manufacturer (P = .382), and preoperative VAS score (P = .362) were not of influence. DISCUSSION: The results of this study show that an extended deltopectoral approach for RSA is safe. Selected reflection of the anterior deltoid muscle improved exposure and prevented anterior deltoid muscle injury followed by reattachment. Patients had similar functional scores preoperatively and at 24 months postoperatively compared with a comparative group. Furthermore, ultrasound evaluation showed intact reattachments.

A biomechanical analysis of double-screw, double-button, and screw-button fixation constructs in patient-specific instrument-guided Latarjet procedure.

BACKGROUND: The Latarjet coracoid transfer procedure reliably stabilizes the glenohumeral joint for shoulder instability. However, complications such as graft osteolysis, nonunion and fracture continue to affect patient clinical outcomes. The double-screw (SS) construct is regarded as the gold standard method of fixation. SS constructs are associated with graft osteolysis. More recently, a double-button technique (BB) has been suggested to minimize graft-related complications. However, BB constructs are associated with fibrous nonunion. To mitigate this risk, a single screw combined with a single button (SB) construct has been proposed. It is thought that this technique incorporates the strength of the SS construct and allows micromotion superiorly to mitigate stress shielding-related graft osteolysis. AIMS: The primary aim of this study was to compare the failure load of SS, BB, and SB constructs under a standardized biomechanical loading protocol. The secondary aim was to characterize the displacement of each construct throughout testing. METHODS: Computed tomography scans of 20 matched-pair cadaveric scapulae were performed. Specimens were harvested and dissected free of soft tissue. SS and BB techniques were randomly assigned to specimens for matched-pair comparison with SB trials. A patient-specific instrument (PSI)-guided Latarjet procedure was performed on each scapula. Specimens were tested using a uniaxial mechanical testing device under cyclic loading (100 cycles, 1 Hz, 200 N/s) followed by a load-to-failure protocol (0.5 mm/s). Construct failure was defined by graft fracture, screw avulsion, and/or graft displacement of more than 5 mm. RESULTS: Forty scapulae from 20 fresh frozen cadavers with a mean age of 69.3 years underwent testing. On average, SS constructs failed at 537.8 N (SD 296.8), whereas BB constructs failed at 135.1 N (SD 71.4). SB constructs required a significantly greater load to fail compared with BB constructs (283.5 N, SD 162.8, P = .039). Additionally, SS (1.9 mm, IQR 0.87) had a significantly lower maximum total graft displacement during the cyclic loading protocol compared with SB (3.8 mm, IQR 2.4, P = .007) and BB (7.4 mm, IQR 3.1, P < .001) constructs. CONCLUSION: These findings support the potential of the SB fixation technique as a viable alternative to SS and BB constructs. Clinically, the SB technique could reduce the incidence of loading-related graft complications seen in the first 3 months of BB Latarjet cases. The study is limited to time-specific results and does not account for bone union or osteolysis.