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Purpose: Cerebral Palsy (CP) often presents with a sweeping thoracolumbar scoliosis and pelvic obliquity. With severe pelvic obliquity, the ribs come into contact with the high side of the oblique pelvis, termed rib-on-pelvis deformity (ROP). ROP can result in costo-iliac impingement, or pain associated with ROP, and can also adversely affect breathing and sitting balance. The goal of this study was to evaluate whether CP patients with ROP have worse health-related quality of life (HRQOL) before surgery and a greater improvement in HRQOL after surgery., Methods: A retrospective analysis of a prospectively collected, multicenter, international registry was performed for all nonambulatory patients with CP treated with spinal fusion with at least two-year follow-up. HRQOL was measured via the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILD) questionnaire domains (0 = most disability, 100 = least disability). ROP was defined as having a rib distal to the superior portion of the iliac crest on preop upright radiographs. The ROP group and control group without ROP were compared regarding six domain scores and total score of CPCHILD. Multiple linear regression was used to control for curve apex location, major coronal Cobb angle, type of tone, and pelvic obliquity., Results: 340 patients met inclusion criteria (52% female, mean age 14.0 years). The mean major coronal Cobb angle was 81 degrees and mean pelvic obliquity was 22 degrees. 176 patients (51.8%) had ROP while 164 patients (48.2%) did not. ROP was independently associated with worse preoperative Positioning/Transfers/Mobility (PTM), Comfort & Emotions (C&E), and total CPCHILD score via the CPCHILD questionnaire (p < 0.05). Patients with preoperative ROP experienced a greater improvement in the C&E and PTM domains as well as total CPCHILD score than patients without ROP (p < 0.05)., Conclusion: CP patients with rib-on-pelvis deformity experience more pain and worse HRQOL than patients without this deformity. These patients experienced a greater improvement in HRQOL after spinal fusion measured via the CPCHILD questionnaire., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

Background: Despite representing over half of all pediatric patella fractures, inferior pole patellar sleeve fractures (PSFs) are a relatively uncommon pediatric injury. As a result, existing literature on PSFs is limited to case reports and small case series. The purpose of this study was to evaluate the radiographic and clinical characteristics of operatively treated PSFs as well as outcomes following surgical management., Methods: A retrospective review of all inferior pole PSFs requiring surgery from 2007 to 2023 was performed at a single urban tertiary care children's hospital. Cases were identified using diagnostic and billing codes. Patient demographics, injury characteristics, surgical techniques, and postoperative rehabilitation practices were recorded. Regional skeletal maturity, fracture characteristics, and postreduction patellar height were recorded. Postoperative complications were recorded and categorized using the modified Clavien-Dindo Classification System (CDS)., Results: Thirty-eight inferior pole PSFs were identified meeting study criteria. The majority of patients were male (86.8%), and the mean age at injury was 11.0 years (range: 7.2 to 15.0). Mean BMI was 21.1. Radiographically, the majority of patients were Epiphyseal Fusion Stage 0 (nonunion), with a median postreduction Caton-Deschamps index (CDI) of 1.2 (IQR: 1.1 to 1.3). These fractures were predominantly treated with suture-based fixation (84%). Postoperative immobilization varied within the cohort, and the initiation of knee ROM was permitted at a median of 3.5 (IQR: 2.0 to 4.6) weeks. All patients regained full range of motion and straight leg raise without extensor lag, and return-to-sport was achieved by a median of 17.6 weeks (IQR: 12.8 to 30.3). Complications occurred in 10 (26.3%) patients, with 3 (7.9%) requiring a return to the OR (CDS Grade III)., Conclusions: Inferior pole PSFs appear to occur most commonly among prepubertal males of normal BMI and normal patellar height. Despite variable rehabilitation protocols, operative management resulted in restoration of extensor mechanism function. Eight percent of patients experienced complications requiring unplanned surgery. This large series improves our understanding of the epidemiology, injury characteristics, and postoperative outcomes of an operatively treated cohort of a rare injury pattern., Level of Evidence: Level IV., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Recent research suggests that synovial fluid neutrophil-to-lymphocyte ratio (SF-NLR) is a superior diagnostic for pyogenic septic arthritis (SA) in adults compared with synovial fluid white blood cell count (SF-WBC) ≥50,000 cells/μL or ≥90% polymorphonuclear leukocytes (SF-%PMN). Other research also indicates that the neutrophil-to-lymphocyte ratio in the blood (B-NLR) may be of diagnostic significance. However, it is not known whether these findings extend to the pediatric population., Methods: Medical records at a large urban tertiary-care children's hospital were queried for emergency department visits between 2012 and 2023, where synovial fluid (SF) analysis was performed to evaluate for SA of the hip or knee. Patients 18 years old and above were excluded. The "conventional composite test" (CCT) for SA was considered positive if SF analysis showed any of the following: (1) SF-WBC ≥50,000 cells/μL, (2) ≥90% PMNs, or (3) organisms reported on gram stain. Patients with aspirate and/or operating room (OR) cultures (or supplemental testing, ie, nucleic acid identification) revealing an offending organism were considered to have culture-positive septic arthritis (CPSA). The remaining patients were considered culture-negative (CN). Serum and SF test data were analyzed to assess their diagnostic utility in identifying CPSA. Receiver operating characteristic (ROC) curves were examined to compare the predictive value of SF-NLR and B-NLR versus conventional indicators of SA., Results: A total of 394 patients met the inclusion criteria. In all, 58.6% (n=231) were male, 67.5% (n=266) involved the knee, and 20.1% (n=79) had CPSA. Those with CPSA had higher ESR and CRP compared with CN patients (P<0.01). Bivariate testing did not show a difference in SF-NLR or B-NLR between those with CPSA and CN patients (P=0.93 and 0.37, respectively). The CCT showed 91% sensitivity and 35% specificity using conventional thresholds. ROC analysis showed that SF-WBC was superior to SF-NLR and B-NLR in the diagnosis of CPSA (AUC=0.71 vs. 0.50 and 0.53, respectively; both P<0.01). Among CCT (+) patients who ended up culture negative, Lyme testing was positive in 48.8% (100/205)., Conclusion: In contrast to adults, SF-NLR and B-NLR were not found to be strong diagnostic indicators of SA of the hip or knee in pediatric patients. This may be because competing diagnoses in children come with systemic inflammatory responses similar to that seen in pyogenic SA, while noninfectious conditions that might represent the major alternate diagnoses in adults do not increase systemic inflammatory markers as significantly. Given the high incidence of Lyme disease seen among patients in this study, this topic should be further studied at pediatric centers outside Lyme-endemic areas to better understand the generalizability of these findings., Significance: Despite excitement regarding SF-NLR and B-NLR as diagnostics for adult SA, these criteria appear less useful in the diagnosis of pyogenic SA in pediatric patients in Lyme-endemic areas., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While prior research provided thorough analysis of the epidemiology of brachial plexus birth injury (BPBI) from 1997 to 2012, recent trends are unknown. The goal of this study was to update the understanding of the epidemiology and risk factors for BPBI., Methods: Installments of the Kids' Inpatient Database (1997 to 2019) were used to estimate BPBI incidence in the United States in comparison to several independent variables over time. An interaction between cesarean (C-) section and newborn weight was explored by defining BPBI rates in a stratified manner. A logistic regression model accounting for this interaction was developed to produce odds ratios for independent factors. Lastly, the temporal relationship between BPBI rates and C-section rates was explored using linear regression., Results: BPBI rates were steady around 0.9 to 1.1 per 1000 live births between 2006 and 2019. C-section rates were similarly stable between 32.3% and 34.0% over this period. Stratified analysis indicated C-section delivery was protective against BPBI across newborn weight classes, but the magnitude of this protective value was highest among newborns with macrosomia. Shoulder dystocia was the strongest risk factor for BPBI in the logistic regression model [adjusted odds ratio (AOR): 56.9, P<0.001]. The AOR for a newborn with macrosomia born through C-section (AOR: 0.581, 95% CI: 0.365-0.925) was lower than that for a normal weight newborn born vaginally (AOR: 1.000, P=0.022). Medicaid insurance coverage (AOR: 1.176, 95% CI: 1.124-1.230, P<0.001), female sex (AOR: 1.238, 95% CI: 1.193-1.283, P<0.001), and non-White race (AOR: 1.295, 95% CI: 1.237-1.357, P<0.001) were independent risk factors for BPBI. Over time, the rate of BPBI correlated very strongly with the rate of C-section (R2=0.980)., Conclusions: While BPBI and C-section rates were relatively stable after 2006, BPBI incidence strongly correlated with C-section rates. This highlights the need for close surveillance of BPBI rates as efforts to lower the frequency of C-section evolve. Female, Black, and Hispanic newborns and children with Medicaid insurance experience BPBI at a higher rate, a finding which could direct future research and influence policy., Level of Evidence: Level IV-case series., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hardware removal (HR) is one of the most common surgical procedures in pediatric orthopaedics. Surgeons advocate for HR for a variety of reasons, including to limit peri-implant fracture risk, restore native anatomy for adult reconstruction surgery, permit bone growth and development, and mitigate implant-related pain/irritation. To our knowledge, no recent study has investigated the characteristics and complications of HR in pediatric orthopaedics. The goal of this study is to report the prevalence and complications of hardware removals across all of pediatric orthopaedic surgery., Methods: A retrospective case series was conducted of all hardware removals from 2012 to 2023 performed at a single urban tertiary-care children's hospital. Cases were identified using CPT codes/billing records. Spinal hardware and cases for which hardware was either implanted or explanted at an outside hospital were excluded. Patient demographic and clinical data were recorded. For patients with multiple hardware removals, each case was recorded independently., Results: A total of 2585 HR cases for 2176 children met study criteria (57.7% male; mean age 12.3±4.4 y). The median postoperative follow-up time was 1.7 months (interquartile range: 0.6 to 6.9). The most common sites of hardware removal were the femur/knee (32.7%), tibia/fibula/ankle (19.3%), and pelvis/hip (18.5%). The most common complications included sustained, new-onset postoperative pain (2.6%), incomplete hardware removal (1.6%), and perioperative fracture (1.4%). The overall complication rate of hardware removal was 9.5%. Eighty-eight percent of patients who underwent hardware removal for pain experienced pain relief postoperatively. HR >18 months after insertion had a 1.2x higher odds of overall complication (P=0.002) and 3x higher odds of incomplete removal/breakage (P<0.001) than hardware removed 9 to 18 months after insertion., Conclusions: The overall complication rate of hardware removal across a large series in the pediatric population was 9.5%. Despite hardware removal being one of the most common and often routine procedures in pediatric orthopaedics, the complication rate is not benign. Surgeons should inform patients and families about the likelihood of success and the risks of incomplete removal during the informed consent process., Level of Evidence: IV., Competing Interests: J.B.A. is a consultant for DePuy Synthes. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Skin carcinoma, including malignant melanoma, basal, squamous, and Merkel cell carcinoma, present significant healthcare challenges. Conventional treatments like surgery and chemotherapy suffer from limitations like non-specificity, toxicity, and adverse effects. The upcoming treatments are dominated by nano-sized delivery systems, which improve treatment outcomes while minimizing side effects. Moving ahead, targeted nanoparticles allow localized delivery of drugs at tumor site, ensuring minimal damage to surrounding tissues., Areas Covered: This review explores various targeting strategies for specific types of skin cancers. The strategies discussed include nanocarrier-mediated targeted delivery with multiple types of ligands like aptamers, antibodies, peptides, and vitamins and their advantages in skin cancer. Upcoming cutting-edge technologies such as smart delivery systems, microneedle-assisted delivery and three-dimensional printed scaffolds have also been discussed in detail. The findings in this review are summarized from databases like PubMed, Scopus, Web of Science, ClinicalTrials.gov, NIH, and articles published between 2005 and 2024 that discuss targeted therapy for skin cancer., Expert Opinion: Specific cancer-targeting strategies promise personalized treatments, improving response rates and reducing need for intensive therapies. The review highlights various challenges, their solution, and economic aspects in this dynamic field. It further emphasizes the potential for specialized strategies to revolutionize skin cancer treatment.

Objective: Most prior investigations on adverse outcomes after open reduction (OR) for developmental dysplasia of the hip (DDH) have focused on avascular necrosis, redislocation, and residual dysplasia. To our knowledge, no previous study has investigated risk factors for stiffness, an underappreciated source of postoperative morbidity. The goals of this study were to define the entity more clearly and evaluate the prevalence and risk factors for arthrofibrosis after OR for DDH., Methods: A retrospective study was conducted, including all open hip reductions for DDH performed by a single surgeon from 2009 to 2022. Preoperative anteroposterior pelvic radiographs were used to calculate superior displacement, which was defined as the distance from the highest point of the proximal femoral metaphysis to the Hilgenreiner line, normalized by pelvic width. Cases treated with premature postoperative bracing cessation and/or referral to physical therapy with a resolution of stiffness within 6 months were categorized as mild arthrofibrosis. Cases that required >6 months of formal physical therapy for persistent range of motion concerns, manipulation under anesthesia, and/or inpatient rehabilitation admission were categorized as significant arthrofibrosis., Results: This study included 170 hips with a mean age of 21.6 months (range: 6.1 to 93.6 mo) and a mean follow-up of 46.8 months. 156 ORs (91.8%) were done through an anterior approach. Sixty-four patients (37.6%) had a concomitant isolated pelvic osteotomy, and 34 (20.0%) had both pelvic and femoral osteotomies. During the postoperative course, 109 patients (64.1%) had no arthrofibrosis, 38 (22.4%) had mild stiffness, and 23 (13.5%) had significant arthrofibrosis. On multivariable analysis, older age, superior displacement, and concomitant pelvic osteotomy were associated with any degree of arthrofibrosis (P< 0.05). Children older than 18 months or with dislocations higher than 16% of pelvic width had a 4.7 and 2.7 times higher risk, respectively, of experiencing some degree of stiffness postoperatively., Conclusions: Older age, high dislocations, and concomitant pelvic osteotomy without femoral shortening are risk factors for stiffness after OR for DDH. Surgeons should counsel families about the risk of postoperative stiffness, which occurred to some degree in 36% of our patients., Level of Evidence: Level IV., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neuromuscular early-onset scoliosis (N-EOS) often presents with a long sweeping thoracolumbar scoliosis and pelvic obliquity. With severe pelvic obliquity, the ribs come into contact with the high side of the pelvis, termed rib-on-pelvis deformity (ROP). The goal of this study is to evaluate whether ROP is associated with reported pain and other health-related quality of life (HRQOL) measures. We hypothesize that ROP is associated with increased pain and negative HRQOL., Methods: A multicenter international registry was queried for all nonambulatory patients with N-EOS from 2012 to 2022. Both surgical and nonsurgical patients were included. ROP was classified as a binary radiographic assessment of preoperative (surgical patients) and most recent follow-up (nonsurgical patients) upright radiographs. Reported pain and other HRQOL measures were assessed through the 24-Item Early Onset Scoliosis Questionnaire (EOSQ-24). Patients with nonupright radiographs or EOSQ-24 questionnaires and corresponding radiographs >4 months apart were excluded., Results: Totally, 225 patients (8.4±3.1 y, 55% female) were included. The median major curve was 63.3 (IQR: 40.6 to 81.2) degrees and median pelvic obliquity was 15.5 degrees (IQR: 8.8 to 26.4). Eighty-three patients (37%) had ROP. ROP was associated with both frequency (P<0.001) and severity (P<0.001) of pain. ROP was associated with worse general health (P=0.01), increased difficulty with vocalization (P=0.02), increased frequency of shortness of breath (P=0.002), and increased difficulty sitting upright (P=0.04). Regarding overall EOSQ-24 domains, ROP was associated with worse general health, pain/discomfort, pulmonary function, and physical function (P<0.01). In a subanalysis of 76 patients who underwent surgical intervention with at least 2 years of follow-up, patients with preoperative ROP experienced significantly greater improvements in both frequency (P=0.004) and severity (P=0.001) of pain than the patients without preoperative ROP at 2 years postoperatively., Conclusions: The overall incidence of ROP in N-EOS is about 37%. ROP is associated with greater pain and worse HRQOL through the EOSQ-24 questionnaire. Furthermore, these patients experienced a greater reduction in pain after surgery. Clinicians and parents must be aware that ROP is possibly a pain generator, but responds positively to surgical intervention., Level of Evidence: Level III., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Skin carcinoma is one of the most prevalent types of carcinomas. Due to high incidence of side effects in conventional therapies (radiotherapy and chemotherapy), photodynamic therapy (PDT) has gained huge attention as an alternate treatment strategy. PDT involves the administration of photosensitizers (PS) to carcinoma cells which produce reactive oxygen species (ROS) on irradiation by specific wavelengths of light that result in cancer cells' death via apoptosis, autophagy, or necrosis. Topical delivery of PS to the skin cancer cells at the required concentration is a challenge due to the compounds' innate physicochemical characteristics. Nanocarriers have been observed to improve skin permeability and enhance the therapeutic efficiency of PDT. Polymeric nanoparticles (NPs), metallic NPs, and lipid nanocarriers have been reported to carry PS successfully with minimal side effects and high effectiveness in both melanoma and non-melanoma skin cancers. Advanced carriers such as quantum dots, microneedles, and cubosomes have also been addressed with reported studies to show their scope of use in PDT-assisted skin cancer treatment. In this review, nanocarrier-aided PDT in skin cancer therapies has been discussed with clinical trials and patents. Additionally, novel nanocarriers that are being investigated in PDT are also covered with their future prospects in skin carcinoma treatment., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Rheumatoid Arthritis (RA) is a chronic, inflammatory, auto-immune disease that is majorly associated with the degradation of the synovial linings of the joints. It is a progressive disease that reduces the life span in affected individuals. Nanoparticles involving hyaluronic acid (HA) have gained the limelight for designing target-specific and more effective drug delivery options for RA. HA is found abundantly in the synovial fluid and acts as a natural ligand for the CD44 receptors. The targeted delivery approach using CD44 as the target can help in minimizing off-target drug distribution. These HA-based surface-decorated nanocarriers, hydrogels, and MNs are cutting-edge strategies that promise tailored delivery, fewer side effects, and more patient adherence to address the common issues associated with RA therapy. Considering the above facts, this review attempts to discuss the role of HA in making more effective formulations for therapeutic delivery in treating RA. Additionally, it provides a comprehensive overview of the potential advancements, mainly in treating RA by HA-based topical, transdermal, and parenteral drug delivery systems, with relevant case studies. The existing difficulties and potential paths for future research on HA-based non-conventional formulations for the management of RA are also discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Humeral head osteonecrosis in the pediatric patients most often occurs in patients with underlying hemoglobinopathies, exposure to chronic corticosteroids, or after trauma. The purpose of this study was to perform a systematic review evaluating the prevalence, clinical characteristics, and management of humeral head osteonecrosis in the pediatric population., Methods: PubMed, Ovid MEDLINE, and Scopus were screened with the terms "osteonecrosis," "avascular necrosis," "pediatric," and "proximal humerus" on January 10, 2024. A total of 218 studies were screened, and 74 studies were evaluated for eligibility. Studies that reported on the prevalence and/or management of pediatric humeral head osteonecrosis were included. The systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines., Results: Twelve studies met inclusion criteria: four retrospective case series, three prospective case series, one retrospective cohort study, one retrospective case-control study, and three case reports. A majority of the studies (67%) discussed chemotherapy-induced osteonecrosis of the humeral head. A total of 77 patients (106 shoulders) with humeral head osteonecrosis were identified. The overall prevalence of osteonecrosis of the humeral head across eight studies examining at-risk populations (underlying hemoglobinopathies or undergoing chemotherapy) was 2%. Intra-articular steroid injections, physical therapy, and activity modification are effective conservative management strategies. Additionally, core decompression and hemiarthroplasty are surgical treatment options., Conclusions: The prevalence of osteonecrosis of the humeral head is low even among at-risk populations with associated medical conditions. A variety of conservative and surgical treatment options have been described, but no comparative evaluations of these modalities has been conducted., Level of Evidence: IV., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

The perpetuity of cancer prevalence at a global level calls for development of novel therapeutic approaches with improved targetability and reduced adverse effects. Conventional cancer treatments have a multitude of limitations such as nonselectivity, invasive nature, and severe adverse effects. Chemotherapy is also losing its efficacy because of the development of multidrug resistance in the majority of cancers. To address these issues, selective targeting-based approaches are being explored for an effective cancer treatment. Mitochondria, being the moderator of a majority of crucial cellular pathways like metabolism, apoptosis, and reactive oxygen species (ROS) homeostasis, are an effective targeting site. Mitochondria-targeted photodynamic therapy (PDT) has arisen as a potential approach in this endeavor. By designing photosensitizers (PSs) that preferentially accumulate in the mitochondria, PDT offers a localized technique to induce cytotoxicity in cancer cells. In this review, we intend to explore the crucial principles and challenges associated with mitochondria-targeted PDT, including variability in mitochondrial function, mitochondria-specific PSs, targeted nanocarrier-based monotherapy, and combination therapies. The hurdles faced by this emerging strategy with respect to safety, optimization, clinical translation, and scalability are also discussed. Nonetheless, mitochondria-targeted PDT exhibits a significant capacity in cancer treatment, especially in combination with other therapeutic modalities. With perpetual research and technological advancements, this treatment strategy is a great addition to the arsenal of cancer treatment options, providing better tumor targetability while reducing the damage to surrounding healthy tissues. This review emphasizes the current status of mitochondria-targeted PDT, limitations, and future prospects in its pursuit of safe and efficacious cancer therapy.

Wound dressings act as a physical barrier between the wound site and the external environment, preventing additional harm; choosing suitable wound dressings is essential for the healing process. Polysaccharide biopolymers have demonstrated encouraging findings and therapeutic prospects in recent decades about wound therapy. Additionally, polysaccharides have bioactive qualities like anti-inflammatory, antibacterial, and antioxidant capabilities that can help the process of healing. Due to their excellent tissue adhesion, swelling, water absorption, bactericidal, and immune-regulating properties, polysaccharide-based bio-adhesive films have recently been investigated as intriguing alternatives in wound management. These films also mimic the structure of the skin and stimulate the regeneration of the skin. This review presented several design standards and functions of suitable bio-adhesive films for the healing of wounds. Additionally, the most recent developments in the use of bio-adhesive films as wound dressings based on polysaccharides, including hyaluronic acid, chondroitin sulfate, dextran, alginate, chitosan, cellulose, konjac glucomannan, gellan gum, xanthan gum, pectin, guar gum, heparin, arabinogalactans, carrageen, and tragacanth gum, are thoroughly discussed. Lastly, to create a road map for the function of polysaccharide-based bio-adhesive films in advanced wound care, their clinical performances and future challenges in making bio-adhesive films by three-dimensional bioprinting are summarized., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: For decades, finding effective long-term or disease-modifying treatments for skin disorders has been a major focus of scientists. The conventional drug delivery systems showed poor efficacy with high doses and are associated with side effects, which lead to challenges in adherence to therapy. Therefore, to overcome the limitations of conventional drug delivery systems, drug delivery research has focused on topical, transdermal, and intradermal drug delivery systems. Among all, the dissolving microneedles have gained attention with a new range of advantages of drug delivery in skin disorders such as breaching skin barriers with minimal discomfort and its simplicity of application to the skin, which allows patients to administer it themselves., Areas Covered: This review highlighted the insights into dissolving microneedles for different skin disorders in detail. Additionally, it also provides evidence for its effective utilization in the treatment of various skin disorders. The clinical trial status and patents for dissolving microneedles for the management of skin disorders are also covered., Expert Opinion: The current review on dissolving microneedles for skin drug delivery is accentuating the breakthroughs achieved so far in the management of skin disorders. The output of the discussed case studies anticipated that dissolving microneedles can be a novel drug delivery strategy for the long-term treatment of skin disorders.

The tumor is an uncontrolled growth of tissue that can be localized (benign) or possesses the capability of metastasis (malignant). The conventional methods of tumor diagnosis, such as acupuncture, endoscopy, and histopathology, and treatment methods, such as injections, chemotherapy, surgery, and radiotherapy, are invasive, expensive, and pose severe safety and management issues for the patients. Microneedle technology is a recently developed approach for active transdermal drug delivery. It is minimally invasive, self-administrable, bypasses the first-pass effect, and effectively delivers chemotherapeutics and drugs at low doses, thus, overcoming the drawbacks of conventional delivery systems. This review provides an idea of the types, materials utilized in the fabrication, and techniques used for the preparation of microneedles (MNs), as well as their application in tumor diagnosis and treatment. Additionally, emphasis is given to the case studies related to MNs-assisted tumor therapy, such as photothermal therapy, gene therapy, photodynamic therapy, chemotherapy, immunotherapy, and various combination therapies. MNs also serve as a tool for diagnosis by the bio-sampling of blood and interstitial skin fluid, as well as biosensing various cancer biomarkers. The combined therapy and diagnostics provide theranostic MNs for enhanced and personalized tumor therapy. The limitations and prospects of MNs development are also discussed.

Nanocarriers have the utmost significance for advancements in drug delivery and nanomedicine technology. They are classified as polymer-based nanocarriers, lipid-based nanocarriers, viral nanoparticles, or inorganic nanoparticles, depending on their constituent parts. Lipid-based nanocarrier systems have gained tremendous attention over the years because of their noteworthy properties like high drug-loading capacity, lower toxicity, better bioavailability and biocompatibility, stability in the gastrointestinal tract, controlled release, simpler scale-up, and validation process. Nanocarriers still have some disadvantages like poor drug penetration, limited drug encapsulation, and poor targeting. These disadvantages can be overcome by their surface modification. Surface-modified nanocarriers result in controlled release, enhanced penetration efficiency, and targeted medication delivery. In this review, the authors summarize the numerous lipid-based nanocarriers and their functionalization through various surface modifiers such as polymers, ligands, surfactants, and fatty acids. Recent examples of newly developing surface-modified lipid-based nanocarrier systems from the available literature, along with their applications, have been compiled in this work., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Graphene-tethered ZnO nanocomposites with rod shapes and oval-shaped 5-fluorouracil-loaded graphene-supported ZnO nanohybrids were synthesized using one pot wet chemical bottom up coprecipitation method. The presence of hexagonal nanophase of ZnO lattice with surface-tethered graphene sheets were confirmed using XRD pattern and supportive UV-Vis and FTIR spectrum. XRD data of these nanocomposites were matched with TEM images which proved the hexagonal ZnO core maintained even after surface tailoring with graphene and drug loading. These porous nanocomposites were loaded with anticancer drug 5-fluorouracil for enhancement in anticancer activity on breast cancer MCF-7 cells. The optical, morphological and phase physicochemical characterizations of the nanohybrids were performed using techniques as UV-Vis, FTIR, XRD spectrometry, and TEM microscopic analysis. The nanocomposites did not only exhibit biocompatibility but also pH responsive in vitro delivery applied for anticancer therapy on the basis of spectrometric MTT assay following sustained drug release with zero-order Peppas release kinetics. These nanocomposites exhibited higher anticancer activity on MCF-7 cells than free drug after in vitro MTT assay. On the basis of these demonstrations, these newer nanocomposites find future biomedical applications in pH-responsive drug delivery., (© 2022. The Author(s), under exclusive licence to Islamic Azad University.)

Objective: The association between accidents and subsequent work unit safety perceptions was assessed to address cognitive and behavioral changes following accidents., Background: Many studies attempt to predict accident rates using measures of work unit safety, but effects vary considerably. Conversely, this study examined whether recent accidents may be positively associated with work unit safety perceptions, as suggested by behavioral learning mechanisms (increases in safety investments following accidents) or cognitive mechanisms (defensive attributions regarding accident causality)., Method: Lagged squadron-level accident experience was correlated with work unit safety perceptions obtained through a 61-question safety climate survey administered to 6,361 individuals in U.S. Navy flight squadrons., Results: Positive associations between minor or intermediately severe accidents and future safety climate scores were found, although no effect was found for major accidents., Conclusion: We suggest that accident history should be considered when examining work unit safety perceptions because recent accidents may be associated with higher safety climate scores. We did not find that this varies systematically with accident severity, and longitudinal research on additional samples is needed to further test this possibility., Application: This research may be used to refine measurement of work unit safety and to examine impacts of accidents or safety violations on workers' cognitive processes and group behavioral changes.