An investigation of nano- and micron-sized carriers based on calcium carbonate and polylactic acid for oral administration of siRNA.

BACKGROUND: Oral delivery of small interfering RNAs (siRNAs) draws significant attention, but the gastrointestinal tract (GIT) has many biological barriers that limit the drugs' bioavailability. The aim of this work was to investigate the potential of micro- and nano-sized CaCO3 and PLA carriers for oral delivery of siRNA and reveal a relationship between the physicochemical features of these carriers and their biodistribution. RESEARCH DESIGN AND METHODS: In vitro stability of carriers was investigated in simulated gastric and intestinal fluids. Toxicity and cellular uptake were investigated on Caco-2 cells. The biodistribution profiles of the developed CaCO3 and PLA carriers were examined using different visualization methods, including SPECT, fluorescence imaging, radiometry, and histological analysis. The delivery efficiency of siRNA loaded carriers was investigated both in vitro and in vivo. RESULTS: Micro-sized carriers were accumulated in the stomach and later localized in the colon tissues. The nanoscale particles (100-250 nm) were distributed in the colon tissues. nPLA was also detected in small intestine. The developed carriers can prevent siRNA from premature degradation in GIT media. CONCLUSION: Our results reveal how the physicochemical properties of the particles, including their size and material type can affect their biodistribution profile and oral delivery of siRNA.

Biomimetic Entropy-Dominant Molecular Hinges with Picomolar Affinity.

Molecular hinges are ubiquitous in both natural and artificial supramolecular systems. A major challenge to date, however, has been simultaneously achieving high thermodynamic and kinetic stability. Here, we employ host-enhanced intramolecular charge-transfer interactions to mediate entropy-favored complexation between a flexible AB2-type guest and a macrocyclic host, forming a new type of molecular hinge with an ultrahigh picomolar binding affinity (Ka > 1012 M-1). This entropy-promoted hinge modulates photoisomerization, exhibiting a substantial preference for the E-isomer, which is further demonstrated to mirror the natural retinal-opsin cycle, promoting the sensitization of visible light. This work unveils an efficient approach to exploit entropy-dominant architectures for the design of hierarchical molecular systems.

Outcomes following Humeral Head Autograft Glenoid Reconstruction in Primary Reverse Total Shoulder Arthroplasty.

BACKGROUND: Patients with severe glenoid bone loss are at increased risk for poor implant fixation, scapular notching, dislocation, joint kinematic disturbances, and prosthetic failure following reverse total shoulder arthroplasty (rTSA). Glenoid bone grafting has proven useful when performing rTSA in patients with inadequate glenoid bone stock, although the current literature is limited. The purpose of this study is to evaluate clinical outcomes in patients with significant glenoid deformity undergoing primary rTSA with one-stage glenoid reconstruction using a humeral head autograft. METHODS: A database of prospectively enrolled patients was reviewed to identify patients who underwent primary rTSA with humeral head autograft (n=40) between 2008 and 2020 by six high-volume shoulder arthroplasty surgeons with minimum two-year follow-up. Variables studied included demographics, medical comorbidities, range of motion (ROM), Constant score, American Shoulder and Elbow Surgeons (ASES) score, pain score, patient satisfaction, glenoid deformity, revisions and complications. Preoperative glenoid deformity was characterized using glenoid version and beta-angles, measured on computed tomography (CT). Improvement at final follow-up was compared to a matched control group of 120 standard primary rTSA patients. Following the post hoc Bonferroni correction, an adjusted alpha value of 0.004 was used to define statistical significance. RESULTS: Forty patients were included with a mean follow-up of 5.3 (range, 2.0-13.2) years. Patients exhibited a mean preoperative glenoid retroversion and beta-angle of 29° and 80°, respectively. At final follow-up, patients who received a graft exhibited lower mean scores for active external rotation (25° vs. 39°; p = 0.001) in comparison to those who did not receive a graft. No differences were observed in active abduction (p = 0.029), active forward elevation (p = 0.009), active internal rotation (p = 0.147), passive external rotation (p = 0.082), Global Shoulder Function score (p = 0.157), Constant score (p = 0.036), ASES score (p = 0.009), or pain score (p = 0.186) between groups. Seven patients (17.5%) exhibited complications of which the most common being aseptic glenoid loosening (15%). CONCLUSION: This study demonstrates that patients undergoing primary rTSA with autogenous humeral head autograft for severe glenoid deficiency experience postoperative improvements in ROM and functional outcome scores that exceeded the minimal clinically important difference and substantial clinical benefit but inferior to matched controls. This suggests that glenoid reconstruction using a resected humeral head autograft is an effective strategy when conducting primary rTSA in patients with significant glenoid deformity.

Silent corticotroph adenomas demonstrate predilection for sphenoid sinus, cavernous sinus, and clival invasion compared to other subtypes.

BACKGROUND AND OBJECTIVE: Nonfunctional pituitary neuroendocrine tumors (PitNETs) exhibit wide variability in growth pattern based on subtype. Silent corticotroph adenomas (SCAs) demonstrate aggressive growth compared to other nonfunctional adenomas (NFPAs), especially into the cavernous sinus. In this study, we sought to characterize other growth patterns of SCAs in comparison to NFPAs. METHODS: We performed a retrospective analysis of all patients with nonfunctional PitNETs treated with surgical resection via endoscopic endonasal approach (EEA) at a single institution from August 1, 2018, to May 11, 2024. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) were reviewed to determine extension into the suprasellar space, sphenoid sinus, cavernous sinus, and clivus. RESULTS: Ninety-one patients were included, including 20 SCAs and 71 NFPAs. SCAs demonstrated significantly greater rates of growth into the sphenoid sinus (55.0% vs. 23.94%, p=0.013), clivus (65.0% vs. 16.9%, p<0.0001), and cavernous sinus (defined as Knosp grade 3 or 4; 55.0% vs. 23.35%, p=0.016). Other NFPAs were more likely to grow into the suprasellar space (92.96% vs. 75.0%, p=0.038). Tumor volume was similar between groups (11.93 cm3 vs. 9.06 cm3, p=0.2). CONCLUSIONS: Silent corticotroph PitNETs demonstrate predilection for invasion of bony structures, with higher rates of growing through the sellar floor into the sphenoid sinus, growing posteroinferiorly into the clivus, and laterally into the cavernous sinuses. Other nonfunctional PitNETs tended to follow the path of least resistance, growing superiorly into the suprasellar space. These differences in growth patterns may account for some of the clinical challenges of treating silent corticotroph PitNETs.

Cell-in-cell phenomena of intracellular neutrophils in a recurrent pleomorphic xanthoastrocytoma.

We describe a case of a young patient with a recurrent pleomorphic xanthoastrocytoma (PXA) showing unusual cell-in-cell (CiC) phenomena. We observed mostly viable but also necrotic neutrophils engulfed within tumor cells. The recurrent tumor was immunopositive for BRAFV600E mutant protein and showed CDKN2 homozygous deletions typical of PXA. Both genetic alterations were also reported in the original primary tumor. Unlike the original tumor that was GFAP and Olig-2 immunopositive, the recurrent neoplasm was largely negative for GFAP and Olig-2 suggesting dedifferentiation. The large malignant cells that contained the neutrophils were negative for histiocytic and lymphohematopoietic markers. Whereas CDKN2 homozygous deletion is common in PXA, its presence is rare in histiocytic neoplasms. Both reactive astrocytes and glial neoplasms very rarely may engulf neutrophils in a process resembling emperipolesis or cellular cannibalism. Future work may clarify which type of CiC pathway is involved.

Machine Learning ADME Models in Practice: Four Guidelines from a Successful Lead Optimization Case Study.

Optimization of the ADME properties and pharmacokinetic (PK) profile of compounds is one of the critical activities in any medicinal chemistry campaign to discover a future clinical candidate. Finding ways to expedite the process to address ADME/PK shortcomings and reduce the number of compounds to synthesize is highly valuable. This article provides practical guidelines and a case study on the use of ML ADME models to guide compound design in small molecule lead optimization. These guidelines highlight that ML models cannot have an impact in a vacuum: they help advance a program when they have the trust of users, are tuned to the needs of the program, and are integrated into decision-making processes in a way that complements and augments the expertise of chemists.

4f-Orbital mixing increases the magnetic susceptibility of Cp'3Eu.

Traditional models of lanthanide electronic structure suggest that bonding is predominantly ionic, and that covalent orbital mixing is not an important factor in determining magnetic properties. Here, 4f orbital mixing and its impact on the magnetic susceptibility of Cp'3Eu (Cp' = C5H4SiMe3) was analyzed experimentally using magnetometry and X-ray absorption spectroscopy (XAS) methods at the C K-, Eu M5,4-, and L3-edges. Pre-edge features in the experimental and TDDFT-calculated C K-edge XAS spectra provided unequivocal evidence of C 2p and Eu 4f orbital mixing in the π-antibonding orbital of a' symmetry. The charge-transfer configurations resulting from 4f orbital mixing were identified spectroscopically by using Eu M5,4-edge and L3-edge XAS. Modeling of variable-temperature magnetic susceptibility data showed excellent agreement with the XAS results and indicated that increased magnetic susceptibility of Cp'3Eu is due to removal of the degeneracy of the 7F1 excited state due to mixing between the ligand and Eu 4f orbitals.

Long shared haplotypes identify the Southern Urals as a primary source for the 10th century Hungarians.

During the Hungarian Conquest in the 10th century CE, the early medieval Magyars, a group of mounted warriors from Eastern Europe, settled in the Carpathian Basin. They likely introduced the Hungarian language to this new settlement area, during an event documented by both written sources and archaeological evidence. Previous archaeogenetic research identified the newcomers as migrants from the Eurasian steppe. However, genome-wide ancient DNA from putative source populations has not been available to test alternative theories of their precise source. We generated genome-wide ancient DNA data for 131 individuals from candidate archaeological contexts in the Circum-Uralic region in present-day Russia. Our results tightly link the Magyars to people of the Early Medieval Karayakupovo archaeological horizon on both the European and Asian sides of the southern Urals. Our analyes show that ancestors of the people of the Karayakupovo archaeological horizon were established in the Southern Urals by the Iron Age and that their descendants persisted locally in the Volga-Kama region until at least the 14th century.

The molecular basis of cereal mixed-linkage ß-glucan utilization by the human gut bacterium Segatella copri.

Mixed-linkage ß(1,3)/ß(1,4)-glucan (MLG) is abundant in the human diet through the ingestion of cereal grains, and is widely associated with healthful effects on metabolism and cholesterol levels. MLG is also a major source of fermentable glucose for the human gut microbiota (HGM). Bacteria from the Family Prevotellaceae are highly represented in the HGM of individuals who eat plant rich diets, including certain indigenous people and vegetarians in post-industrial societies. Here, we have defined and functionally characterized an exemplar Prevotellaceae MLG Polysaccharide Utilization Locus (MLG-PUL) in the type-strain Segatella copri (syn. Prevotella copri) DSM 18205 through transcriptomic, biochemical, and structural biological approaches. In particular, structure-function analysis of the cell-surface glycan-binding proteins (SGBP) and glycoside hydrolases (GH) of the S. copri MLG-PUL revealed the molecular basis for glycan capture and saccharification. Notably, syntenic MLG-PULs from human gut, human oral, and ruminant gut Prevotellaceae are distinguished from their counterparts in Bacteroidaceae by the presence of a ß(1,3)-specific endo-glucanase from Glycoside Hydrolase Family 5, Subfamily 4 (GH5_4) that initiates MLG backbone cleavage. The definition of a family of homologous MLG-PULs in individual species enabled a survey of nearly 2000 human fecal microbiomes using these genes as molecular markers, which revealed global population-specific distributions of Bacteroidaceae- and Prevotellaceae-mediated MLG utilization. Altogether, the data presented here provide new insight into the molecular basis of ß-glucan metabolism in the HGM, as a basis for informing the development of approaches to improve the nutrition and health of humans and other animals.

Discovery and lectotype designation of Longitarsuscalifornicus (Motschulsky) (Coleoptera, Chrysomelidae, Galerucinae, Alticini).

The lectotype of Longitarsuscalifornicus (Motschulsky, 1845) is designated, described, and illustrated. An illustrated key to eight light-colored Longitarsus species known to occur in the western United States is presented. A brief history of Russian entomological collecting in North America during the first half of 19th century, with specimens preserved in Zoological Museum of Moscow University, Moscow and Zoological Institute, St. Petersburg, is provided.

Reduction in rate of implant waste associated with robotic-assisted total hip arthroplasty.

Aims: Implant waste during total hip arthroplasty (THA) represents a significant cost to the USA healthcare system. While studies have explored methods to improve THA cost-effectiveness, the literature comparing the proportions of implant waste by intraoperative technology used during THA is limited. The aims of this study were to: 1) examine whether the use of enabling technologies during THA results in a smaller proportion of wasted implants compared to navigation-guided and conventional manual THA; 2) determine the proportion of wasted implants by implant type; and 3) examine the effects of surgeon experience on rates of implant waste by technology used. Methods: We identified 104,420 implants either implanted or wasted during 18,329 primary THAs performed on 16,724 patients between January 2018 and June 2022 at our institution. THAs were separated by technology used: robotic-assisted (n = 4,171), imageless navigation (n = 6,887), and manual (n = 7,721). The primary outcome of interest was the rate of implant waste during primary THA. Results: Robotic-assisted THA resulted in a lower proportion (1.5%) of implant waste compared to navigation-guided THA (2.0%) and manual THA (1.9%) (all p < 0.001). Both navigated and manual THA were more likely to waste acetabular shells (odds ratio (OR) 4.5 vs 3.1) and polyethylene liners (OR 2.2 vs 2.0) compared to robotic-assisted THA after adjusting for demographic and perioperative factors, such as surgeon experience (p < 0.001). While implant waste decreased with increasing experience for procedures performed manually (p < 0.001) or with navigation (p < 0.001), waste rates for robotic-assisted THA did not differ based on surgical experience. Conclusion: Robotic-assisted THAs wasted a smaller proportion of acetabular shells and polyethylene liners than navigation-guided and manual THAs. Individual implant waste rates vary depending on the type of technology used intraoperatively. Future studies on implant waste during THA should examine reasons for non-implantation in order to better understand and develop methods for cost-saving.

Influence of Electron Donors on the Charge Transfer Dynamics of Carbon Nanodots in Photocatalytic Systems.

Carbon nanodots (CNDs) are nanosized light-harvesters emerging as next-generation photosensitizers in photocatalytic reactions. Despite their ever-increasing potential applications, the intricacies underlying their photoexcited charge carrier dynamics are yet to be elucidated. In this study, nitrogen-doped graphitic CNDs (NgCNDs) are selectively excited in the presence of methyl viologen (MV2+, redox mediator) and different electron donors (EDs), namely ascorbic acid (AA) and ethylenediaminetetraacetic acid (EDTA). The consequent formation of the methyl viologen radical cation (MV•+) is investigated, and the excited charge carrier dynamics of the photocatalytic system are understood on a 0.1 ps-1 ms time range, providing spectroscopic evidence of oxidative or reductive quenching mechanisms experienced by optically excited NgCNDs (NgCNDs*) depending on the ED implemented. In the presence of AA, NgCNDs* undergo oxidative quenching by MV2+ to form MV•+, which is short-lived due to dehydroascorbic acid, a product of photoinduced hole quenching of oxidized NgCNDs. The EDTA-mediated reductive quenching of NgCNDs* is observed to be at least 2 orders of magnitude slower due to screening by EDTA-MV2+ complexes, but the MV•+ population is stable due to the irreversibly oxidized EDTA preventing a back reaction. In general, our methodology provides a distinct solution with which to study charge transfer dynamics in photocatalytic systems on an extended time range spanning 10 orders of magnitude. This approach generates a mechanistic understanding to select and develop suitable EDs to promote photocatalytic reactions.

G protein-coupled receptor (GPCR) pharmacogenomics.

The field of pharmacogenetics, the investigation of the influence of one or more sequence variants on drug response phenotypes, is a special case of pharmacogenomics, a discipline that takes a genome-wide approach. Massively parallel, next generation sequencing (NGS), has allowed pharmacogenetics to be subsumed by pharmacogenomics with respect to the identification of variants associated with responders and non-responders, optimal drug response, and adverse drug reactions. A plethora of rare and common naturally-occurring GPCR variants must be considered in the context of signals from across the genome. Many fundamentals of pharmacogenetics were established for G protein-coupled receptor (GPCR) genes because they are primary targets for a large number of therapeutic drugs. Functional studies, demonstrating likely-pathogenic and pathogenic GPCR variants, have been integral to establishing models used for in silico analysis. Variants in GPCR genes include both coding and non-coding single nucleotide variants and insertion or deletions (indels) that affect cell surface expression (trafficking, dimerization, and desensitization/downregulation), ligand binding and G protein coupling, and variants that result in alternate splicing encoding isoforms/variable expression. As the breadth of data on the GPCR genome increases, we may expect an increase in the use of drug labels that note variants that significantly impact the clinical use of GPCR-targeting agents. We discuss the implications of GPCR pharmacogenomic data derived from the genomes available from individuals who have been well-phenotyped for receptor structure and function and receptor-ligand interactions, and the potential benefits to patients of optimized drug selection. Examples discussed include the renin-angiotensin system in SARS-CoV-2 (COVID-19) infection, the probable role of chemokine receptors in the cytokine storm, and potential protease activating receptor (PAR) interventions. Resources dedicated to GPCRs, including publicly available computational tools, are also discussed.

Mesial temporal lobe epilepsy and hippocampal sclerosis associated with BRAFV600E mutant neurons in the Cornu Ammonis: an uncertain pathogenesis and a diagnostic challenge.

Mesial temporal lobe epilepsy (MTLE) is a common cause of seizures, and hippocampal sclerosis (HS) is the predominant subtype. BRAFV600E mutations in MTLE-HS have only been reported infrequently. Herein, we illustrate the neurologic, radiological, and histopathological details of a patient with MTLE-HS and BRAFV600E mutant neurons. A 31-year-old male with medically refractory epilepsy presented with magnetic resonance imaging (MRI) and electroencephalography (EEG) findings typical of mesial temporal sclerosis without a mass lesion. The surgical specimens showed ILAE Type 1 HS with neurons immunopositive for BRAFV600E mutant protein distributed along the Cornu Ammonis (CA) curvature. Instead of the normal mostly perpendicular orientation of pyramidal neurons relative to the hippocampal surface, the BRAF mutant neurons were often oriented in a parallel manner. On CD34 immunostaining, sparse clusters or nodules of CD34+ stellate cells and single immunopositive stellate cells were identified. BRAFV600E or CD34 immunopositive cells were less than 1 % of total cells. The patient responded well to surgery with no further seizures after 2 years and occasional auras. Hippocampal BRAF mutant non-expansive lesion (HBNL) has been used to describe such lesions with preserved cytoarchitecture and without overt tumor mass. Others may argue for the dual pathology of HS with early ganglioglioma. Whether pre-neoplastic lesions or early tumors, these cases are important for understanding early glioneuronal tumorigenesis and suggest that BRAFV600E studies should be routinely performed on MTLE-HS cases in the setting of clinical trials. With next-generation sequencing, a FANCL deletion was detected in almost half of the alleles in our case, suggesting that many of the histologically normal-appearing cells of the hippocampus contain this alteration. FANCL mutations can result in cytogenetic anomalies and defective DNA repair and therefore may underlie the development of a low frequency BRAF alteration.

Effects of Low-Frequency Deep Brain Stimulation in Bilateral Zona Incerta for a Patient With Tremor and Cerebellar Ataxia.

Background: Whether low-frequency deep brain stimulation (DBS) in the caudal zona incerta (cZi) can improve cerebellar ataxia symptoms remains unexplored. Case Report: We report a 66-year-old man initially diagnosed with essential tremor and subsequently developed cerebellar ataxia after bilateral cZi DBS implantation. We tested the effects of low-frequency DBS stimulations (sham, 10 Hz, 15 Hz, 30 Hz) on ataxia severity. Discussion: Low-frequency cZi DBS improves ataxic speech at 30 Hz, but not at 10 Hz or 15 Hz in this patient. Low-frequency DBS did not improve gait or stance. Therefore, low-frequency stimulation may play a role in treating ataxic speech. Highlights: The finding of this case study suggests that bilateral low-frequency DBS at 30 Hz in the caudal zona incerta has the potential to improve ataxic speech but has limited impact on gait and stance. The involvement of zona incerta in speech warrants further investigation.

Flow diversion of cerebral aneurysms in Type I osteogenesis imperfecta: A case report of the first two treatments in humans.

Osteogenesis imperfecta (OI) predisposes individuals to easy bone fracture, vessel fragility, and platelet dysfunction. We report the first known case of neurointerventional treatment with flow diversion of intracranial aneurysms in a patient with OI. A 62 year-old female with known OI Type I, history of >40 lifetime bone fractures and hypertension, underwent workup for transient ischemic attacks revealing a 4-mm right A1 segment aneurysm in 2016. Perioperative dual antiplatelet therapy was aspirin 81 mg and clopidogrel 37.5 mg daily. Tri-axial access was utilized to deploy a 3.5 × 16-mm Pipeline Flex device without complication. Two-month follow-up revealed Raymond I (O'Kelly Marotta I) obliteration of the aneurysm. Five-year follow-up revealed a de novo left-sided 3-mm A1-A2 junction aneurysm. A 4 × 12-mm Surpass Evolve was placed without complication. Six-month follow-up revealed Raymond I (O'Kelly Marotta I) obliteration of the second aneurysm. The patient remained asymptomatic at all follow-up visits.

Analysis of Flutianil and OC56635 Residues in Hemp Cannabis Matrices by LC-MS/MS.

In this paper, we present analytical methodologies for the determination of the thiazolidine fungicide flutianil (trade name GATTEN) and its primary metabolite OC56635 in hemp cannabis matrices. A total of nine crop matrices were tested: whole seed, fiber, flower buds, hemp hearts, hemp seed oil, hemp meal, hemp flour, ethanol extracted CBD resin (CBD-E), and supercritical CO2 extracted CBD resin (CBD-C). Processing of the CBD-E and CBD-C crop fractions was carried out in-house using methods detailed herein. Field sample analysis utilized sequential extractions, stacked solid phase extraction (SPE) column cleanups, and evaporation to prepare the samples for LC-MS/MS quantitation. Method validations for each fraction were carried out using untreated hemp matrices over a minimum of three levels, with lowest levels of method validation (LLMV) of 0.010 µg/g for all fractions except the CBD resins, for which LLMV was 0.020 µg/g. Flutianil-treated samples from nine field sites were collected from several crop production regions and analyzed to determine the distribution of incurred flutianil and OC56635 residues within the different hemp matrices. This data was generated in support of nationwide registration with the United States Environmental Protection Agency (USEPA).

Isolation and Crystallographic Characterization of an Octavalent Co2O2 Diamond Core.

High-valent cobalt oxides play a pivotal role in alternative energy technology as catalysts for water splitting and as cathodes in lithium-ion batteries. Despite this importance, the properties governing the stability of high-valent cobalt oxides and specifically possible oxygen evolution pathways are not clear. One root of this limited understanding is the scarcity of high-valent Co(IV)-containing model complexes; there are no reports of stable, well-defined complexes with multiple Co(IV) centers. Here, an oxidatively robust fluorinated ligand scaffold enables the isolation and crystallographic characterization of a Co(IV)2-bis-µ-oxo complex. This complex is remarkably stable, in stark contrast with previously reported Co(IV)2 species that are highly reactive, which demonstrates that oxy-Co(IV)2 species are not necessarily unstable with respect to oxygen evolution. This example underscores a new design strategy for highly oxidizing transition-metal fragments and provides detailed data on a previously inaccessible chemical unit of relevance to O-O bond formation and oxygen evolution.

Topical bromfenac in VEGF-driven maculopathies: topical review and meta-analysis.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs have the potential to reduce treatment burden and improve outcomes of anti-VEGF therapy for a number of retinal disorders, including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. In this review, we focused on the advantages of topical bromfenac as an adjunct to intravitreal anti-VEGF therapy in VEGF-driven maculopathies. METHODS: Cochrane Library, PubMed, and EMBASE were systematically reviewed to identify the relevant studies of neovascular age-related macular degeneration, diabetic macular edema, macular edema associated with retinal vein occlusion, myopic choroidal neovascularization, and radiation maculopathy which reported changes in central retinal thickness, visual acuity, and the number of anti-VEGF injections needed when anti-VEGF therapy was combined with topical bromfenac. RESULTS: In total, ten studies evaluating bromfenac as an adjunct to anti-VEGF therapy were identified. Five studies were included in meta-analysis of the number of injections and five studies were included in the analysis of changes in central retinal thickness. A statistically significantly lower number of intravitreal injections (p = 0.005) was required when bromfenac was used as an adjunct to anti-VEGF therapy compared to anti-VEGF monotherapy with pro re nata regimen. At the same time, eyes receiving bromfenac as an adjunct to anti-VEGF therapy demonstrated non-inferior outcomes in central retinal thickness (p = 0.07). Except for one study which reported better visual outcomes with combined treatment, no difference in visual acuity or clinically significant adverse effects were reported. CONCLUSIONS: This literature review and meta-analysis showed that topical bromfenac can be considered as a safe adjunct to anti-VEGF therapy with a potential to reduce the treatment burden with anti-VEGF drugs requiring frequent injections without compromising improvement of central retinal thickness or visual acuity.

Meso-Macroporous Hydroxyapatite Powders Synthesized in Polyvinyl Alcohol or Polyvinylpyrrolidone Media.

Mesoporous hydroxyapatite (HA) is widely used in various applications, such as the biomedical field, as a catalytic, as a sensor, and many others. The aim of this work was to obtain HA powders by means of chemical precipitation in a medium containing a polymer-polyvinyl alcohol or polyvinylpyrrolidone (PVP)-with concentrations ranging from 0 to 10%. The HA powders were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, atomic emission spectroscopy with inductively coupled plasma, electron paramagnetic resonance, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The specific surface area (SSA), pore volume, and pore size distributions were determined by low-temperature nitrogen adsorption measurements, and the zeta potential was established. The formation of macropores in powder agglomerates was determined using SEM and TEM. The synthesis in 10% PVP increased the SSA from 101.3 to 158.0 m2/g, while the ripening for 7 days led to an increase from 112.3 to 195.8 m2/g, with the total pore volume rising from 0.37 to 0.71 cm3/g. These materials could be classified as meso-macroporous HA. Such materials can serve as the basis for various applications requiring improved textural properties and may lay the foundation for the creation of bulk 3D materials using a technique that allows for the preservation of their unique pore structure.