Search

ABSTRACT Children delivered by elective, prelabor Cesarean section (C-section) are not exposed to the birth canal microbiota and, in relation to vaginally delivered children, show altered microbiota development. Perturbed microbial colonization during critical early-life windows of development alters metabolic and immune programming and is associated with an increased risk of immune and metabolic diseases. In nonrandomized studies, vaginal seeding of C-section-born neonates partially restores their microbiota colonization to that of their vaginally delivered counterparts, but without randomization, confounding factors cannot be excluded. In a double-blind, randomized, placebo-controlled trial, we determined the effect of vaginal seeding versus placebo seeding (control arm) on the skin and stool microbiota of elective, prelabor C-section-born neonates (n = 20) at 1 day and 1 month after birth. We also examined whether there were between-arm differences in engraftment of maternal microbes in the neonatal microbiota. In relation to the control arm, vaginal seeding increased mother-to-neonate microbiota transmission and caused compositional changes and a reduction in alpha diversity (Shannon Index) of the skin and stool microbiota. The neonatal skin and stool microbiota alpha diversity when maternal vaginal microbiota is provided is intriguing and highlights the need of larger randomized studies to determine the ecological mechanisms and effects of vaginal seeding on clinical outcomes. IMPORTANCE Children delivered by elective C-section are not exposed to the birth canal and show altered microbiota development. Impairing microbial colonization during early life alters metabolic and immune programming and is associated with an increased risk of immune and metabolic diseases. In a double-blind, randomized, placebo-controlled trial, we determined the effect of vaginal seeding on the skin and stool microbiota of elective C-section born neonates and found that vaginal seeding increased mother-to-neonate microbiota transmission and caused compositional changes and a reduction in the skin and stool microbiota diversity. The reduction of neonatal skin and stool microbiota diversity when maternal vaginal microbiota is provided is intriguing and highlights the need of larger randomized studies to determine the ecological mechanisms and effects of vaginal seeding on clinical outcomes.

Corneal transplant is a procedure that aims to replace dysfunctional corneal tissue with a transparent graft and is one of the most widely performed transplant surgeries, but its public and professional awareness is low outside of ophthalmology. Corneal tissue consists of 5 major layers that serve to maintain its structural integrity and refractive shape: the epithelium, Bowman’s layer, the stroma, Descemet’s membrane, and the endothelium. Failure or irreversible damage to any layer of the cornea may be an indication for corneal transplant, and variants of this procedure may be full thickness or selectively lamellar. Complications related to corneal transplantation may occur anywhere from during surgery to years afterward, including rejection, dehiscence, cataract, and glaucoma. Complications should be managed by an ophthalmologist, but other physicians should be aware of prophylactic medications. Topical immunosuppressants and steroids are effective for preventing and treating rejection episodes, whereas there is little evidence to support the use of systemic immunosuppression. Eye protection is recommended for any corneal transplant recipient. Physicians should counsel patients on corneal donation, especially if outside the United States, where donor tissue is in short supply.

The meconium microbiome may provide insight into intrauterine and peripartum exposures and the very earliest intestinal pioneering microbes. Prenatal antibiotics have been associated with later obesity in children, which is thought to be driven by microbiome dependent mechanisms. However, there is little data regarding associations of prenatal or peripartum antibiotic exposure, with or without cesarean section (CS), with the features of the meconium microbiome. In this study, 16S ribosomal RNA gene sequencing was performed on bacterial DNA of meconium samples from 105 infants in a birth cohort study. After multivariable adjustment, delivery mode (p = 0.044), prenatal antibiotic use (p = 0.005) and peripartum antibiotic use (p < 0.001) were associated with beta diversity of the infant meconium microbiome. CS (vs. vaginal delivery) and peripartum antibiotics were also associated with greater alpha diversity of the meconium microbiome (Shannon and Simpson, p < 0.05). Meconium from infants born by CS (vs. vaginal delivery) had lower relative abundance of the genus Escherichia (p < 0.001). Prenatal antibiotic use and peripartum antibiotic use (both in the overall analytic sample and when restricting to vaginally delivered infants) were associated with differential abundance of several bacterial taxa in the meconium. Bacterial taxa in the meconium microbiome were also differentially associated with infant excess weight at 12 months of age, however, sample size was limited for this comparison. In conclusion, prenatal and peripartum antibiotic use along with CS delivery were associated with differences in the diversity and composition of the meconium microbiome. Whether or not these differences in the meconium microbiome portend risk for long-term health outcomes warrants further exploration.

We report a case of phthiriasis palpebrarum in an immunocompetent individual along with the review of the literature. A 61-year-old woman presented with a 2-month history of itching and burning sensation in both eyes. Examination revealed lice and nits anchored to the eyelashes with a mild follicular conjunctival reaction and no evidence of discharge. The patient recovered fully within 2 weeks after manual removal of the lice and crusts along with topical antibiotic ointment and oral ivermectin, with no evidence of lice or nits on follow-up. This study suggests that patients presenting with itching of the eyelids and other asthenopic symptoms should be carefully examined by slit-lamp examination, to not miss out on unusual diagnoses such as found in this case.

Aim: To study if there is an increase in the serum levels of Glial Fibrillary Acidic Protein (GFAP) in patients with glioblastoma so that it can be used as a diagnostic biomarker for these cases. Design: Prospective observational study. Material and Methods: We prospectively examined 193 patients, out of which 25 were controls (patients with degenerative spinal disease or CV junction anomaly), 79 were tumors other than glioma, 45 were histologically proven gliomas except glioblastoma and 44 were histologically proven glioblastomas. Serum was taken from the patients in the pre-operative period. Serum GFAP levels were determined using a biotin-labeled antibody-based sandwich enzyme immunoassay for the quantitative measurement of GFAP in ng/ml. Statistical Analysis: Data analysis was performed by using SPSS (Statistical Package for Social Sciences) version 20:0. Statistical significance was defined as P value < 0.05. Receiver operating characteristic (ROC) curve analysis was used to find the cut-off value of serum GFAP for glioblastoma patients. Results: In Group A (25 controls) and Group B (79 patients with non-glial brain tumors), no patient had detectable levels of GFAP in their serum. Out of the 45 patients with histologically proven gliomas except glioblastoma (Group C), 12 patients had raised serum GFAP levels. Out of the 44 patients with histologically proven glioblastomas (Group D), 38 patients had raised serum GFAP levels while in the remaining 6, the levels of serum GFAP were not detectable. The sensitivity of serum GFAP levels in diagnosing glioblastoma patients was 86.36% and the specificity was 91.95%. The diagnostic accuracy of the test was 90.67%. Conclusions: Serum GFAP is a sensitive and specific marker for glioblastoma and can be a useful pre-operative serum biochemical investigation in differentiating glioblastoma cases from other brain tumors.

With the advent of musculoskeletal ultrasound (US), there has been a paradigm shift in the way rheumatological conditions are detected, quantified and managed. Small joints of the wrist and hand play an important role in the diagnosis and characterization of inflammatory arthritis. Successful scanning of the wrist and hand requires good scanning equipment, thorough knowledge of anatomy and scanning protocols. The dorsal recesses of the wrist, metacarpophalangeal joint, proximal interphalangeal joint and the distal interphalangeal joint are scanned to look for joint effusion, synovial hypertrophy and cortical erosions. The extensor tendons of the wrist and hand have a synovial sheath at the level of the distal radius. The flexor tendons and the median nerve along the volar aspect of the wrist pass through a fibro-osseous tunnel known as the carpal tunnel. US pathologies commonly encountered in inflammatory arthritis have been very well defined in literature, so that there is better reproducibility of the tests and reduction in the inter-observer variation.

Knowledge of the anatomy of the shoulder and its periarticular soft tissues and scanning techniques are essential for successful ultrasound (US) examination of the shoulder. Inflammatory conditions or overuse injuries affecting the periarticular structures are the most common causes of nontraumatic shoulder pain. Dynamic imaging with US is an added advantage and scores over similar cross-sectional imaging modalities. In a routine US examination of the shoulder joint, the extraarticular segment of the long head of biceps, rotator-cuff tendons and their muscle bellies, rotator interval, subacromial-subdeltoid bursa, posterior joint recess, and the acromioclavicular joint are assessed systematically.

Accurate diagnosis and treatment planning are essential for obtaining ideal treatment result in cases involving mandibular incisor extraction. This case report describes a 15-year-old female with balanced soft-tissue profile, peg-shaped maxillary lateral incisors, and moderate mandibular anterior crowding treated with a mandibular incisor extraction. Ideal overbite and overjet were achieved. "Black triangle" formation was avoided due to the bodily movement of mandibular incisors and the use of uprighting springs for ideal axial inclination of mandibular incisors. A mandibular incisor extraction can be an effective treatment option in carefully selected clinical situations.

Tennis leg is caused by a rupture of the medial head of the gastrocnemius muscle, usually at its distal musculotendinous junction region. However, tears in this muscle and its tendon are also included under the term ′tennis leg′. It is seen regularly in practice and is an important cause of a painful calf. The common USG findings include: disruption of the pinnate pattern of the distal medial gastrocnemius, usually near the junction of the triceps surae (which is the echogenic line between the gastrocnemius, the soleus, and the plantaris muscles), fluid tracking along the fascia, adjacent hematoma, and intramuscular tears as well as hematomas. USG is useful for confirming the diagnosis, excluding other causes of a painful calf, for assessing the severity of the disease, and in follow-up.

Cerclage wiring may be used to optimize the stability of intramedullary nail or plate fixations in comminuted proximal femoral fractures, periprosthetic fractures, and other selected cases. In this article, we presented a novel case of iatrogenic sciatic nerve entrapment from cerclage wiring used to supplement intramedullary nail fixation. We also illustrate and highlight the role of ultrasound in assessing the sciatic nerve to make a timely diagnosis.

Summary:. Several studies have linked calcification of the thoracic and lower extremity arterial trunks to an increased risk of developing coronary artery disease (CAD). Calcifications of the radial and/or ulnar artery are regularly identified in hand/wrist x-rays; however, the clinical relevance of these findings as related to identifying subclinical CAD is not well understood. Associations between CAD and upper extremity calcifications have been reported, but the timeline is unclear. The purpose of this study was to evaluate the association between upper extremity arterial calcifications on hand radiographs with CAD by coronary artery calcification (CAC) scoring in patients with no known history of CAD. This is a pilot single-center, prospective, matched cohort study. We included patients with no known history of CAD, related symptoms, or major risk factors. We recruited five patients with calcifications (cal+) and five patients matched by age, race, sex, and medical history but without calcifications (cal−). CAC scores were determined from computed tomography scanning, and lipid profile was evaluated. In the cal+ group, the mean CAC total score was 244.1; in the control (cal−) group, it was 85.2. The mean total cholesterol levels were 220.8 mg per dL and 167 mg per dL in the cal+ and cal− groups, respectively. Two cal+ patients with CAC scores of 937 and 669 died shortly after being enrolled in our study. Preliminary findings suggest that calcifications in the radial or ulnar artery in otherwise asymptomatic patients with no history of CAD may be an independent sign of CAD.

Due to very less bioavailability (20%) of Rosuvastatin calcium, an attempt was made to develop and optimize microemulsion formulation. Capmul MCM, Tween 20 and PEG 400 were selected as oil, surfactant and cosurfactant respectively as the drug is having higher solubility in them. 3:1% w/w S:CoS was selected as it gave higher microemulsion area. Optimized batch (ME-1) was selected having 5% Capmul MCM, 50% Tween 20:PEG 400 and 45% water based on evaluation parameters globule size, zeta potential, PDI, % transmittance. [ABSTRACT FROM AUTHOR]

PURPOSE: Chronic graft-versus-host disease (cGVHD) is a significant cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplant (HCT). The objective of our study was to determine if early assessment of matrix metalloproteinase-9 (MMP-9) and dry eye (DE) symptoms (via the DE Questionnaire-5 [DEQ-5]) had prognostic utility for the development of cGVHD and/or severe DE symptoms after HCT. MATERIALS AND METHODS: This was a retrospective study of 25 individuals who underwent HCT and had MMP-9 (InflammaDry) and DEQ-5 performed on day 100 post-HCT (D + 100). Patients also completed the DEQ-5 at 6, 9, and 12 months post-HCT. The development of cGVHD was determined by chart review. RESULTS: Overall, 28% of patients developed cGVHD over a median follow-up of 229 days. At D + 100, 32% of patients had a positive MMP-9 in at least one eye and 20% had a DEQ-5 ≥6. However, neither the presence of a positive MMP-9 nor a DEQ-5 score ≥6 at D + 100 predicted the development of cGVHD (MMP-9: hazard ratio [HR]: 1.53, 95% confidence interval [CI]: 0.34-6.85, P = 0.58; DEQ-5 ≥6: HR: 1.00, 95% CI: 0.12-8.32, P = 1.00). In addition, neither of these measures predicted the development of severe DE symptoms (DEQ-5 ≥12) over time (MMP-9: HR: 1.77, 95% CI: 0.24-12.89, P = 0.58; DEQ-5 >6: HR: 0.03, 95% CI: 0.00-889.93, P = 0.49). CONCLUSION: Within our small cohort, DEQ-5 and MMP-9 assessment at D + 100 did not predict the development of cGVHD or severe DE symptoms.

Venetoclax is an approved treatment for relapsed/refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). We report a unique case of venetoclax monotherapy used for front-line induction and as a bridge to allogeneic hematopoietic stem cell transplantation (HCT). Venetoclax therapy resulted in rapid complete resolution of skin lesions, however, treatment interruption due to neutropenia led to brisk cancer recurrence. Fortunately, the patient responded to re-challenge and was able to undergo HCT. Venetoclax is active in the first-line treatment setting for BPDCN, however its effect on blood counts and durability of response should be further studied.

Acute macular neuroretinopathy (AMN) is a deep retinal ischemic manifestation. It has been reported after the use of sympathomimetics, childbirth, bee sting, oral contraceptives, flu-like illness, intravenous contrast agents and bodily trauma not directly involving the eyes. We report a case of AMN following blunt ocular trauma. An 18-year-old male presented with an acute history of blurring of vision following blunt trauma to the right eye. Spectral domain optical coherence tomography (SD-OCT) showed hyperreflectivity of the outer nuclear layer with ellipsoid layer disruption. This report highlights AMN as a manifestation of blunt trauma, presence of which may be an indicator of poor visual prognosis.

Several case reports regarding complications of ventriculoperitoneal (VP) shunt have been published, but peroral extrusion of shunt tube is unusual and reported less frequently. A 4-year-old male child with previous history of VP shunt insertion for congenital hydrocephalus along with shunt revisions twice presented with peritoneal end of shunt tube protruding through the mouth following an acute episode of vomiting. He was conscious without any signs of infection or neurologic deficits. The distal portion of the tube was removed uneventfully with the help of upper GI endoscope that, in addition to removal, provided better views for the identification of site and size of perforation. Peroral extrusion of the shunt tube needs immediate treatment that includes removal of extruded shunt tube, treatment of underlying infection, and attention to perforated viscus. We review the possible pathogenesis of this entity and various treatment options.

Colloid cysts are benign cystic lesions characteristically arising from the third ventricle roof close to the foramen of Monro. Although incredibly rare, hemorrhage within a third ventricular colloid cyst is sparsely reported. To the best of our knowledge, no cases of hemorrhage within the fourth ventricle colloid have ever been documented. Here, we present an interesting case describing a hemorrhagic colloid cyst situated within the fourth ventricle of a 55-year-old female patient who presented with symptoms of headache, vomiting, and gait imbalance. The cyst was excised during surgery via a suboccipital microscopic telovelar approach. Our findings led us to the conclusion that, despite being extremely rare, colloid cysts in the fourth ventricle can present with hemorrhagic episodes, which can exacerbate symptoms and hasten neurological decline. As a result, the presence of unusual radiological characteristics in a fourth ventricle lesion should prompt medical practitioners to suspect an atypical colloid cyst. This consideration can be pivotal in making informed surgical decisions. Expedited management and a microsurgical approach are recommended strategies for a better outcome.

Peripheral nerve imaging is a powerful tool in evaluating peripheral neuropathy. This review aims to provide an overview of the anatomy, clinical significance and pathologies of small peripheral nerves, typically less than 2 mm in diameter. High frequency ultrasound probes offer the best assessment of these nerves whilst permitting real-time clinical correlation, while the role of MRI is inherently limited by spatial resolution constraints and the lack of patient contact. This review discusses techniques for sonographic identification, strategies for optimal visualization and common ultrasound-guided procedures., Competing Interests: Declarations: Informed consent for publication and presentation was obtained from the subjects described in this article. Ethical approval was not warranted for presentation of this review article. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objectives: Corneal thinning and perforation are ocular emergencies necessitating urgent intervention to prevent visual impairment or enucleation. Cyanoacrylate tissue adhesive is frequently used to maintain globe integrity in these cases. However, gaps remain in understanding the outcomes of corneal gluing and the factors influencing its efficacy. This case series evaluates the clinical characteristics and outcomes of glue application in corneal thinning and perforation., Methods: A retrospective chart review was conducted on patients treated for corneal thinning and perforation at the University of Florida between January 2012 and May 2023. Demographic data, clinical history, glue application details, and posttreatment outcomes were collected and analyzed., Results: The study included 128 eyes from 125 subjects. Corneal perforation was found in 71 eyes (55.5%), mostly centrally (49.2%). The leading cause of perforation/thinning was microbial infection (45.3%). The average number of glue applications per eye was 1.66. Within 1 month, 23 patients (18.0%) required only glue reapplication, 37 (28.9%) required surgical intervention (regardless of glue reapplication), and 68 (53.1%) required no further treatment. Factors significantly linked to gluing failure (requiring surgery within 1 month) in univariate analysis included large perforation size, microbial infection, ocular surface disorder, single glue application, and indirect application via sterile drape. Multivariate analysis showed that only large perforation size was significantly associated with gluing failure., Conclusion: Corneal glue application is an effective temporizing measure for corneal thinning and perforation, with multiple applications potentially providing added stability to the globe. However, the need for surgical intervention is high., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Superficial venous pseudoaneurysm is rare. Prompt diagnosis is essential to formulate management plan and decrease morbidity. We describe a novel Eccentric Ripple sign of BAARISh for diagnosing venous pseudoaneurysm., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Glycerol kinase deficiency (GKD) is an X-linked recessive disorder due to glycerol kinase ( GK ) gene mutations resulting in hyperglycerolermia, hyperglyceroluria, and "pseudohypertriglyceridemia." In vivo glycerol metabolism has not been assessed in GKD. A 62-year-old man with suspected GKD and his extended family underwent whole exome sequencing and fasting blood work with two modes of lipid measurements: (1) standard lipase-based methodology and (2) nuclear magnetic resonance (NMR). Two overnight fasted men with GKD and a heterozygote female carrier then underwent 13 C 3 -glycerol infusion. Affected family members had a novel two-nucleotide deletion in exon 5 of the GK gene (c.373&#95;374del). Compared to their family members ( n  = 14), men with GKD ( n  = 5) had significantly lower total cholesterol levels (3.72 ± 0.70 vs. 4.77 ± 0.85 mmol/L, p  = 0.024). Compared to NMR, lipase-based assays overreported triglycerides (5.28 ± 1.38 vs. 0.81 ± 0.32, mmol/L, p  < 0.001) and underreported low-density lipoprotein cholesterol values (0.93 ± 0.23 vs. 2.18 ± 0.42 mmol/L, p  = 0.001) in GKD. Men with GKD could not convert glycerol into glucose or triglycerides, which was preserved in the heterozygote carrier. Glycolytic metabolism of glycerol to lactate persisted in GKD, but it was reduced by a magnitude and, possibly, due to homologous glycerol kinases encoded by other genes. In summary, we report a novel GK pathogenic variant; affected men cannot convert circulating glycerol to glucose or triglycerides and have lower cholesterol levels. These results offer a human model for potentially targeting glycerol kinase to treat conditions associated with hyperglycemia and hyperlipidemia and warrant further investigation., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: In patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high-risk features on histopathologic examination. We evaluated the interaction between post-NAT lymph node metrics and AC receipt on survival., Methods: Patients who received NAT followed by pancreatectomy (2010-2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS., Results: Of 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien-Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post-NAT LNP rates were not different, and median LNR was 0.1, in AC and non-AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non-AC (24 vs. 20 months, respectively; p = 0.04)., Conclusions: LNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Herpes zoster ophthalmicus (HZO) occurs when latent varicella zoster virus reactivates in the ophthalmic division of the fifth cranial nerve (CNV1). HZO commonly affects older and immunocompromised patients. This disease is considered an ophthalmic emergency due to the wide range of associated ocular symptoms, including severe chronic pain and vision loss. HZO is typically a clinical diagnosis due to its classic presentation of a unilateral vesicular eruption in the dermatomes corresponding to CNV1. Timely treatment is imperative to minimize ocular morbidity in HZO, given that ocular involvement is present in 50% of affected patients., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The US Food and Drug Administration (FDA) approved talazoparib with enzalutamide for first-line treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC)., Patients and Methods: The approval was based on the HRR gene-mutated (HRRm) population of TALAPRO-2, a randomized, double-blind trial that randomly assigned 1,035 patients with mCRPC to receive enzalutamide with either talazoparib or placebo. Two cohorts enrolled sequentially: an all-comer population (Cohort 1), followed by an HRRm-only population (Cohort 2). The independent primary end points were radiographic progression-free survival (rPFS) per blinded independent central review (BICR) in Cohort 1 (all-comers) and in the combined HRRm population (all HRRm patients from Cohorts 1 and 2). Overall survival (OS) was a key secondary end point., Results: A statistically significant improvement in rPFS by BICR was demonstrated in both the all-comers cohort and the combined HRRm population, with hazard ratio (HR) of 0.63 (95% CI, 0.51 to 0.78; P < .0001) and 0.45 (95% CI, 0.33 to 0.61; P < .0001), respectively. In an exploratory analysis of the 155 patients with BRCA -mutated ( BRCA m) mCRPC, rPFS HR was 0.20 (95% CI, 0.11 to 0.36). In the non-HRRm/unknown stratum of Cohort 1 (n = 636), the rPFS HR was 0.70 (95% CI, 0.54 to 0.89). OS was immature., Conclusion: Despite a statistically significant rPFS improvement in the all-comer cohort, FDA did not consider the magnitude of rPFS clinically meaningful in the context of the broad indication, combination treatment, and safety profile. Approval was therefore limited to patients with HRRm mCRPC, for whom there was a statistically significant and clinically meaningful improvement in rPFS and favorable OS results. This represents the first approval for the first-line treatment of patients with HRRm mCRPC.

Background: Childhood Sjögren's disease is a rare, underdiagnosed, and poorly-understood condition. By integrating machine learning models on a paediatric cohort in the USA, we aimed to develop a novel system (the Florida Scoring System) for stratifying symptomatic paediatric patients with suspected Sjögren's disease., Methods: This cross-sectional study was done in symptomatic patients who visited the Department of Pediatric Rheumatology at the University of Florida, FL, USA. Eligible patients were younger than 18 years or had symptom onset before 18 years of age. Patients with confirmed diagnosis of another autoimmune condition or infection with a clear aetiological microorganism were excluded. Eligible patients underwent comprehensive examinations to rule out or diagnose childhood Sjögren's disease. We used latent class analysis with clinical and laboratory variables to detect heterogeneous patient classes. Machine learning models, including random forest, gradient-boosted decision tree, partial least square discriminatory analysis, least absolute shrinkage and selection operator-penalised ordinal regression, artificial neural network, and super learner were used to predict patient classes and rank the importance of variables. Causal graph learning selected key features to build the final Florida Scoring System. The predictors for all models were the clinical and laboratory variables and the outcome was the definition of patient classes., Findings: Between Jan 16, 2018, and April 28, 2022, we screened 448 patients for inclusion. After excluding 205 patients due to symptom onset later than 18 years of age, we recruited 243 patients into our cohort. 26 patients were excluded because of confirmed diagnosis of a disorder other than Sjögren's disease, and 217 patients were included in the final analysis. Median age at diagnosis was 15 years (IQR 11-17). 155 (72%) of 216 patients were female and 61 (28%) were male, 167 (79%) of 212 were White, and 20 (9%) of 213 were Hispanic, Latino, or Spanish. The latent class analysis identified three distinct patient classes: class I (dryness dominant with positive tests, n=27), class II (high symptoms with negative tests, n=98), and class III (low symptoms with negative tests, n=92). Machine learning models accurately predicted patient class and ranked variable importance consistently. The causal graphical model discovered key features for constructing the Florida Scoring System., Interpretation: The Florida Scoring System is a paediatrician-friendly tool that can be used to assist classification and long-term monitoring of suspected childhood Sjögren's disease. The resulting stratification has important implications for clinical management, trial design, and pathobiological research. We found a highly symptomatic patient group with negative serology and diagnostic profiles, which warrants clinical attention. We further revealed that salivary gland ultrasonography can be a non-invasive alternative to minor salivary gland biopsy in children. The Florida Scoring System requires validation in larger prospective paediatric cohorts., Funding: National Institute of Dental and Craniofacial Research, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Heart, Lung, and Blood Institute, and Sjögren's Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Pathogenic bacteria in the oral cavity or a physiological microbiome imbalance can cause or maintain disease. Thus, this work examined a novel betadine-saline combination for antibacterial and antifungal activities., Materials and Methods: This study was in vitro . Betadine, saline, and their mixtures were tested for Bacillus subtilis , Staphylococcus aureus (gram-positive), Pseudomonas aeruginosa , Escherichia coli , and Aspergillus niger (gram-negative). Pour plate and disc diffusion methods were used to test CFUs, DZI, and RZI for various agent combinations., Results: For Lactobacillus acidophilus , Betadine 90% + saline 10% had the greatest DZI and RZI at 24 and 12 mm, respectively. For E. coli , Betadine 50% + saline 50% had the highest at 16 and 8 mm. Betadine 60% + saline 40% had 14 mm RZI and the highest antifungal activity., Conclusion: The novel betadine-saline antibacterial and antifungal combination performed well. In vivo research should confirm the existing findings., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Objective: This study sought to determine the relationship between right ventricular (RV) function and clinical variables and prognosis in individuals with acute myocardial infarction (AMI) utilizing strain imaging., Materials and Methods: A prospective observational research involving 150 patients who had been admitted with AMI was carried out. Utilizing two-dimensional speckle-tracking strain imaging, RV function was assessed. Age, sex, risk factors, and comorbidities were recorded as clinical parameters. A 12-month follow-up was conducted to assess major adverse cardiovascular events (MACE)., Results: 65% of the study's participants were men, with a mean age of 58.2 years. When compared to a healthy control group, individuals with AMI had significantly lower RV longitudinal strain (RVLS) ( P 0.001). RVLS and left ventricular ejection fraction had a statistically significant connection (r = 0.642, P 0.001). Patients with compromised RVLS had a greater rate of MACE over the follow-up period compared to those with maintained RV function ( P = 0.014)., Conclusion: In conclusion, strain imaging offers useful information for evaluating RV function in patients with AMI. Reduced left ventricular performance and a higher likelihood of unfavorable clinical outcomes are linked to impaired RVLS. Utilizing strain imaging to detect RV dysfunction early can help direct treatment plans and enhance patient outcomes., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Introduction: Alteration in the various markers is seen in diabetic nephropathy (DN). In the current research, four different markers were evaluated and were examined for their diagnostic value in the nephropathic type 2 diabetes patients., Methods: A prospective clinical trial was piloted with diabetic male subjects with nephropathy. The subjects were followed up for 9 months. Thirty subjects were recruited as type 2 diabetes mellitus patients without nephropathy as controls. The interventional groups were grouped again as microalbuminuria, normoalbuminuria, and hyperfiltration. All of them underwent testing for urinary biomarkers like urine protein, ACR, HbA1C, and estimated glomerular filtration rate (eGFR). Correlation and logistic regression were used to compare all diagnostic tests across various groupings., Results: The greatest area under curve (AUC) values were .90 and .91 for AGT and AGT/Cr, respectively. The AUC, specificity, sensitivity, and cut-off value of AGT/Cr were, respectively, .91, 85%, 91%, and 4.36 mg/g. When using urine as the cut-off, the sensitivity was 42 and 100 for ACR and eGFR both. All other biomarkers had lower values than the AGT. Less than. 50 was evident for NGAL/Cr and NAGL., Conclusions: To identify DN, before the initiation of the albuminuria, compared to other diagnostic markers, urinary AGT demonstrated a greater diagnostic value. Further research is suggested to corroborate the findings., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Psoriasis, an auto-inflammatory disorder, has major manifestations in the skin but can affect other organs. Currently, this condition has no cure, and the treatments include anti-inflammatory medications. Nanoparticles are widely used for drug delivery and have found successful applications in therapy for cancer and infectious diseases. Nanoparticles can also be used to deliver anti-inflammatory drugs to sites of inflammation. Moreover, some nanotechnology platforms possess intrinsic anti-inflammatory properties and may benefit the therapy of inflammation-driven disorders. Herein, we present a protocol to study nanotechnology concepts' anti-inflammatory properties in a chemically-induced psoriasis model., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The purpose of this study was to compare the efficacy, and ocular pharmacokinetics of a new 0.04% w/v bis in die means twice a day (BID) ophthalmic solution and marketed 0.05% w/v quater in die means four times a day (QID) ophthalmic emulsion of difluprednate in New Zealand white (NZW) rabbits. Methods: The preclinical proof of concept was established in paracentesis-induced acute inflammation, endotoxin-induced acute uveitis, and bovine serum albumin-induced chronic uveitis in NZW rabbit animal models. A comparison of clinical score, total cell count, and total protein was performed to determine efficacy. An ocular pharmacokinetic study was conducted to study the influence of the vehicle on the ocular absorption of the drug. Results: In both uveitis models, the new solution formulation and marketed emulsion formulation inhibited total clinical score, total cell count, PGE 2, and total protein significantly more than the placebo and lipopolysaccharide (disease control) groups and were comparable. In an ocular pharmacokinetic study, the C max and AUC 0-t of difluoroprednisolone 17-butyrate in humor were ∼2-fold higher after 14 days' instillation of new solution formulation (0.04% w/v, BID) compared with 14 days' instillation of marketed emulsion (0.05% w/v, QID). Conclusions: The study demonstrated that the efficacy of the solution formulation at a lower dose and reduced dosing regimen were comparable to that of the emulsion formulation. The reduction in strength and regimen may result in improved patient adherence and outcomes.

Oxidative stress is commonly observed in cells following exposure to nanoparticles. Both negative (e.g., cytotoxicity and inflammation) and beneficial (e.g., anti-inflammatory and tumor growth inhibiting) responses have been linked in the literature to oxidative stress, emphasizing the importance of developing methodologies to study this phenomenon in cells following their exposure to nanoparticles. In the protocol described herein, primary human T cells isolated from the peripheral blood of healthy donor volunteers are treated with nanoparticles and controls, and the generation of reactive oxygen species is detected by flow cytometry using CM-H 2 DCFDA reagent., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The complement system is complex and includes two main components: the systemic or plasma complement and the so-called intracellular complement or complosome. The complement proteins expressed by the liver and secreted into blood plasma compose the plasma complement system, whereas complement proteins expressed by and functioning inside the cell represent the intracellular complement. The complement system plays an essential role in host defense; however, complement activation may lead to pathologies when uncontrolled. When such undesirable activation of the plasma complement occurs in response to a drug product, it leads to immediate-type hypersensitivity reactions independent of immunoglobulin E. These reactions are often called complement activation-related pseudoallergy (CARPA). In addition to the blood plasma, the complement protein C3 is found in many cells, including lymphocytes, monocytes, endothelial, and even cancer cells. The activation of the intracellular complement generates split products, which are exported from the cell onto the membrane. Since the activation of the intracellular complement in T lymphocytes was found to correlate with autoimmune disorders, and growing evidence is available for the involvement of T lymphocytes in the development of drug-induced hypersensitivity reactions, understanding the ability of nanomaterials to activate intracellular complement may aid in establishing a long-term safety profile for these materials. This chapter describes a flow cytometry-based protocol for detecting intracellular complement activation by engineered nanomaterials., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)