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Neovascular age-related macular degeneration (nvAMD) is the leading cause of severe vision loss in the elderly in the developed world. While the introduction of therapies targeting vascular endothelial growth factor (VEGF) has provided the first opportunity to significantly improve vision in patients with nvAMD, many patients respond inadequately to current anti-VEGF therapies. It was recently demonstrated that expression of a second angiogenic mediator, angiopoietin-like 4 (ANGPTL4), synergizes with VEGF to promote choroidal neovascularization (CNV) in mice and correlates with reduced response to anti-VEGF therapy in patients with nvAMD. Here, we report that expression of ANGPTL4 in patients with nvAMD increases following treatment with anti-VEGF therapy and that this increase is dependent on accumulation of hypoxia-inducible factor (HIF)-1a in response to inhibition of VEGF/KDR signaling in the retinal pigment epithelium (RPE). We therefore explored HIF-1 inhibition with 32-134D, a recently developed pharmacologic HIF-inhibitor, for the treatment of nvAMD. 32-134D prevented the expression of both VEGF and ANGPTL4 and was at least as effective as aflibercept in treating CNV in mice. Moreover, by preventing the increase in HIF-1a accumulation in the RPE in response to anti-VEGF therapy, combining 32-134D with aflibercept was more effective than either drug alone for the treatment of CNV. Collectively, these results help explain why many patients with nvAMD respond inadequately to anti-VEGF therapy and suggest that the HIF inhibitor 32-134D will be an effective drug--alone or in combination with current anti-VEGF therapies--for the treatment of patients with this blinding disease. [ABSTRACT FROM AUTHOR]

Nanoparticles play a crucial role in the field of nanotechnology, offering different properties due to their surface area attributed to their small size. Among them, silver nanoparticles (AgNPs) have attracted significant attention due to their antimicrobial properties, with applications that date back from ancient medicinal practices to contemporary commercial products containing ions or silver nanoparticles. AgNPs possess broad-spectrum biocidal potential against bacteria, fungi, viruses, and Mycobacterium, in addition to exhibiting synergistic effects when combined with certain antibiotics. The mechanisms underlying its antimicrobial action include the generation of oxygen-reactive species, damage to DNA, rupture of bacterial cell membranes and inhibition of protein synthesis. Recent studies have highlighted the effectiveness of AgNPs against various clinically relevant bacterial strains through their potential to combat antibioticresistant pathogens. This review investigates the proteomic mechanisms by which AgNPs exert their antimicrobial effects, with a special focus on their activity against planktonic bacteria and in biofilms. Furthermore, it discusses the biomedical applications of AgNPs and their potential non-preparation of antibiotic formulations, also addressing the issue of resistance to antibiotics. [ABSTRACT FROM AUTHOR]

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Objective: Rare disease. Background: Neurilemmomas are rare tumors derived from the Schwann cells that comprise the peripheral nerve sheaths. They have a slow growth and rarely display malignancy. Early diagnosis is rare, and the treatment consists by surgical resection. Although robotic-assisted surgery is commonly used for treating retroperitoneal diseases, there are few reports of resection of retroperitoneal and pelvic schwannoma through robotic-assisted surgery. In the present study, we reported a case of complete excision of a benign retroperitoneal schwannoma of the obturator nerve by robotic-assisted surgery. Case Report: A 51-year-old woman was referred by her gynecologist for left pelvic discomfort of a 3-month duration. The physical examination was normal, but a computerized tomography scan of the abdomen and pelvis showed an expansive pelvic lesion in the topography of the left iliac vessels, a hypodense contrast enhancement measuring 4.6Ã--3.4 cm. Magnetic resonance imaging showed an extraperitoneal lesion located medially and inferiorly to the left external iliac vessels, with a size of 4.9Ã--3.7 cm, and of probable neural etiology. Surgical resection of the tumor was recommended because of the diagnostic hypothesis of obturator nerve schwannoma. Conclusions: This case showed that retroperitoneal neurilemmomas are difficult to diagnose owing to a lack of specific symptoms, and the best treatment is complete tumor resection. The use of robotic techniques gives greater dexterity to the surgeon, since it provides high-definition 3-dimensional vision, which can make the removal of retroperitoneal tumors susceptible to minimally invasive resection in a safe and effective way. [ABSTRACT FROM AUTHOR]

Therapies targeting VEGF have proven only modestly effective for the treatment of proliferative sickle cell retinopathy (PSR), the leading cause of blindness in patients with sickle cell disease. Here, we shift our attention upstream from the genes that promote retinal neovascularization (NV) to the transcription factors that regulate their expression. We demonstrated increased expression of HIF-1[alpha] and HIF-2[alpha] in the ischemic inner retina of PSR eyes. Although both HIFs participated in promoting VEGF expression by hypoxic retinal Muller cells, HIF-1 alone was sufficient to promote retinal NV in mice, suggesting that therapies targeting only HIF-2 would not be adequate to prevent PSR. Nonetheless, administration of a HIF-2-specific inhibitor currently in clinical trials (PT2385) inhibited NV in the oxygen-induced retinopathy (OIR) mouse model. To unravel these discordant observations, we examined the expression of HIFs in OIR mice and demonstrated rapid but transient accumulation of HIF-1[alpha] but delayed and sustained accumulation of HIF- 2[alpha]; simultaneous expression of HIF-1[alpha] and HIF-2[alpha] was not observed. Staggered HIF expression was corroborated in hypoxic adult mouse retinal explants but not in human retinal organoids, suggesting that this phenomenon may be unique to mice. Using pharmacological inhibition or an in vivo nanoparticle-mediated RNAi approach, we demonstrated that inhibiting either HIF was effective for preventing NV in OIR mice. Collectively, these results explain why inhibition of either HIF-1[alpha] or HIF-2[alpha] is equally effective for preventing retinal NV in mice but suggest that therapies targeting both HIFs will be necessary to prevent NV in patients with PSR., Introduction Several multicenter randomized controlled clinical trials have demonstrated the benefit of monthly (or bimonthly) injections with biological molecules directed against the vasoactive mediator VEGF to treat macular edema in [...]

Systemic scleroderma is a relatively rare, autoimmune, chronic, and debilitating disease, and its etiology is unknown. The disease is characterized by vasomotor disturbances causing skin and mucosa hardening, hand stiffness, excess production of collagen fibers, and impairment of the internal organs associated with the immune system. Extreme mouth-opening limitation is one of the symptoms in the oral cavity, and compromises dental intervention. One of the fundamental steps when performing a dental procedure is dental arch impression. In the presented clinical case, limited mouth opening hindered the impression accuracy. The objective was to present an alternative impression technique for a patient affected by scleroderma, with limited mouth opening and the need for oral rehabilitation with a removable partial prosthesis in the maxillary arch. An individualized tray was developed with design characteristics that allowed access to the oral cavity and removal, after which it was possible to perform the oral impression, reproducing the areas of interest without causing injury to the oral tissues. The orientation plan was elaborated after obtaining the cast. The teeth were assembled, tested in the mouth, and sent to the laboratory for acrylization. The prosthesis was placed once ready. The alternative impression technique enabled oral rehabilitation of the patient despite the mouth-opening limitation, and provided an accurate impression and a good prosthetic result. [ABSTRACT FROM AUTHOR]

It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly understood. Here, we provide evidence demonstrating that oxidative stress cooperates with hypoxia to synergistically stimulate the accumulation of hypoxia-inducible factor (HIF)-1a in the retinal pigment epithelium (RPE), resulting in increased expression of the HIF-1-dependent angiogenic mediators that promote CNV. HIF-1 inhibition blocked the expression of these angiogenic mediators and prevented CNV development in an animal model of ocular oxidative stress, demonstrating the pathological role of HIF-1 in response to oxidative stress stimulation in neovascular AMD. While human-induced pluripotent stem cell (hiPSC)-derived RPE monolayers exposed to chemical oxidants resulted in disorganization and disruption of their normal architecture, RPE cells proved remarkably resistant to oxidative stress. Conversely, equivalent doses of chemical oxidants resulted in apoptosis of hiPSC-derived retinal photoreceptors. Pharmacologic inhibition of HIF-1 in the mouse retina enhanced--while HIF-1 augmentation reduced--photoreceptor apoptosis in two mouse models for oxidative stress, consistent with a protective role for HIF-1 in photoreceptors in patients with advanced dry AMD. Collectively, these results suggest that in patients with AMD, increased expression of HIF-1a in RPE exposed to oxidative stress promotes the development of CNV, but inadequate HIF-1a expression in photoreceptors contributes to the development of GA. [ABSTRACT FROM AUTHOR]

Clinical involvement of the nervous system in visceral larva migrans due to Toxocara is rare, although in experimental animals the larvae frequently migrate to the brain. A review of the literature from the early 50's to date found 29 cases of brain involvement in toxocariasis. In 20 cases, various clinical and laboratory manifestations of eosinophilic meningitis, encephalitis, myelitis or radiculopathy were reported. We report two children with neurological manifestations, in which there was cerebrospinal fluid pleocytosis with marked eosinophilia and a positive serology for Toxocara both in serum and CSF. Serology for Schistosoma mansoni, Cysticercus cellulosae, Toxoplasma and cytomegalovirus were negative in CSF, that was sterile in both cases. Improvement of signs and symptoms after specific treatment (albendazole or thiabendazole) was observed in the two cases. A summary of data described in the 25 cases previously reported is presented and we conclude that in cases of encephalitis and myelitis with cerebrospinal fluid pleocytosis and eosinophilia, parasitic infection of the central nervous system should be suspected and serology should be performed to establish the correct diagnosis and treatment.

This study proposed to evaluate the influence of the crystallization firing process and the hydrothermal degradation on the bond strength between different reinforced glass-ceramics and resin cement. Material and Methods: zirconia-reinforced lithium silicate (ZLS) and lithium disilicate (LD) were divided into six groups according to aging simulation (baseline or after thermocycling) and restorative approach (ZLS without firing; ZLS with firing; LD with firing). ZLS and LD surfaces were etched with 5% hydrofluoric acid for 30 s and 20 s, respectively, and then received a layer of silane coupling agent (Monobond-N). Then, cylinders of resin cement (1 mm diameter × 2 mm height) were bonded onto their surfaces. The baseline samples were immersed in distilled water for 24 h before the microshear bond strength (µSBS) test, while half of the specimens were tested after 6000 cycles of thermocycling aging. The types of failures were analyzed through stereomicroscopic and scanning electron microscope. The failure modes were classified as adhesive, predominantly adhesive, cohesive in ceramic, or cohesive in cement. The µSBS data were analyzed by two-way ANOVA and Tukey's test. A restorative approach (p = 0.000) and aging (p = 0.000) affected the bond strength. The highest bond-strength values were observed in the ZLS without the optional crystallization firing. The most frequent failures were adhesive and predominantly adhesive. The cementation of zirconia-reinforced lithium silicate without the optional crystallization firing process leads to high bond-strength values with resin cement. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine the effect of calving to timed artificial insemination (C‐TAI) interval on fertility of Bos taurus and Bos indicus cows and to determine the best C‐TAI interval to include postpartum cows in TAI programs in each genotype (B. taurus and B. indicus). In experiment 1, a retrospective study was performed, with data from 2,709 TAI in Bos taurus and Bos indicus cows with different C‐TAI intervals. There was a positive linear effect of C‐TAI interval on the pregnancy probability (p <.0001). However, there was no effect or interaction with the genotype. When C‐TAI intervals were grouped in classes, pregnancy rate differed in groups (p <.05). Receiver operating characteristic (ROC) analysis was performed, and it was observed that 52 days would be the better C‐TAI interval to maximize fertility in beef cows. According to the previous result, we further stratified into two C‐TAI interval groups (≤ 52 days or > 52 days). Cows with C‐TAI longer than 52 days (C‐TAI > 52) had greater pregnancy rate (56%) than cows with short C‐TAI (46%; p <.01). In experiment 2, 18 postpartum beef cows were subjected to TAI protocol at different C‐TAI intervals (n = 6 cows per group): 40, 60 or 80 days postpartum. Cows with 60 days of C‐TAI had a greater preovulatory follicle diameter than cows with 80 days postpartum (p <.05). The C‐TAI interval did not affect (p >.05) the ovulation rate nor the proportion of endometrial polymorphonuclear leucocytes. We conclude that C‐TAI interval affects pregnancy rate in both Bos taurus and Bos indicus. We recommend a C‐TAI interval longer than 52 days to increase fertility of beef cows included in TAI programs. [ABSTRACT FROM AUTHOR]

Roux-en-Y gastric bypass, a procedure proven effective for treating morbid obesity and metabolic disorders, carries the risk of complications such as the formation of internal hernias. These hernias are often difficult to diagnose and can be potentially fatal because they can cause structural obstruction. Most internal hernias occur in the jejunojejunostomy mesentery space, followed by Petersen's space hernias, although herniation at other locations can also occur. Our case report presents an example of a rare internal hernia after laparoscopic Roux-en-Y gastric bypass. A 36-year-old woman presented with an uncommon internal hernia located between the liver and alimentary loop, resulting in the formation of a new space and consequently incarcerating the entire biliopancreatic loop. This type of internal hernia is rare and has not been reported in the literature, indicating that this is the first report of such a case. In this case, we realized that the diagnosis was challenging and imaging examinations could not help determine the etiology of the pain and obstruction. Therefore, videolaparoscopy revealed an uncommon hernia formed by firm adhesion between the hepatic segment III and the alimentary loop mesentery. Our case is an example of an internal hernia that was not detected with a normal computed tomography scan of the abdomen and pelvis. Only diagnostic laparoscopy revealed herniation, effectively preventing further complications for the patient. [ABSTRACT FROM AUTHOR]

The physicochemical properties of nanoparticles (NPs) directly influence the colloidal stability and bio‐nano interface, which makes the study of these factors extremely important for NPs applicability. Here, we report the influence of pH and ionic strength in the size, surface charge, and antimicrobial activity of chitosan/rhamnolipid nanoparticles (C/RL‐NPs), synthesized by mixing C and RL in the proportion of 1:1, with the dropwise addition of TPP (sodium tripolyphosphate) in the molar ratio of 1:2.5:1.3, respectively. The obtained NPs were resuspended in different solvents to investigate the ionic strength effect on their stability and antimicrobial activity. By decreasing pH and ionic strength, NPs size was reduced while their surface charge increased. Chitosan nanoparticles (C‐NPs) remained stable in the presence of TPP at acidic pH and low ionic strength, indicating that the modulation of physicochemical conditions for the crosslinking between the two ionic components was an efficient approach to enhance C/RL‐NPs colloidal stability. Thermogravimetric analysis confirmed the interaction between rhamnolipid and chitosan in C/RL‐NPs. The antibacterial activity of C/RL‐NPs against Staphylococcus aureus increased significantly, demonstrating the importance of investigating size and surface charge to dictate the bioactivity properties of such hybrid natural‐based nanomaterial. [ABSTRACT FROM AUTHOR]

Blending chitosan and gelatin, two biodegradable and non-toxic polymers, is a recurrent choice in food coating or biomaterials development. The incorporation of vegetal extracts into chitosan/gelatin films can improve or introduce some properties to these materials. Jatobá resin is a product of Hymenaea genus trees with antimicrobial and anti-inflammatory activities, interesting properties for films applied in several areas. The chitosan degree of acetylation (DA) influences the inter and intramolecular interactions of this polymer and, therefore, also implicates in changes of its properties. This research aims to study the influence of jatobá resin inclusion and chitosan DA modification on chitosan/gelatin films properties. Both jatobá resin and chitosan DA affected physicochemical, antimicrobial and barrier properties of the films, allowing the control of these properties by changes in these parameters. Jatobá resin incorporation and the decrease in chitosan DA significantly improved antimicrobial activity and water vapor permeability of films with the reduction of water solubility and swelling. [Display omitted] • Controlling films properties is feasible by jatobá resin inclusion and DA changes. • Resin addition increases water resistance and permeability of chitosan/gelatin films. • Chitosan/gelatin/jatobá resin films demonstrate high water vapor transmission rate. • Both DA and vegetal resin influence antimicrobial efficacy of chitosan/gelatin films. • Chitosan-based films properties make them ideal candidates as bioactive systems. [ABSTRACT FROM AUTHOR]

Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide. We conducted an observational study of 262 consecutive individuals (n = 344 eyes) with ocular toxoplasmosis who were followed over a 34-month period. Most subjects were T. gondii IgG + /IgM- (n = 242; 92.4%; 317 eyes), and 140 eyes (40.7%) had active lesions. For eyes in which retinal lesions were active at recruitment and best-corrected visual acuity (BCVA) could be measured (n = 133), 21.0% (n = 28) remained blind (BCVA below 20/400) after inflammation resolved. In these eyes, atypical ocular toxoplasmosis (OR 4.99; 95% CI 1.14–22.85; p = 0.0330), macular lesion (OR 9.95; 95% CI 2.45–47.15; p = 0.0019) and any complication (OR 10.26; 95% CI 3.82–30.67; p < 0.0001) were associated with BCVA below 20/200. For eyes with only inactive lesions at recruitment and BCVA measured (n = 178), 28.1% (n = 50) were blind. In these eyes, having at least one lesion larger than one disc-diameter (OR 6.30; 95% CI 2.28–22.46; p = 0.0013) and macular lesion (OR 5.69; 95% CI 2.53–13.54; p < 0.0001) were associated with BCVA below 20/200. Older age (OR 1.02; 95% CI 1.00–1.05; p = 0.0493) and active disease at presentation (OR 4.74; 95% CI 1.95–12.91; p = 0.0011) were associated with recurrences. Additional clinical attention should be directed towards patients with risk factors for poor visual outcome. [ABSTRACT FROM AUTHOR]

In this study, chitosan and gelatin materials incorporated with grape seed (Vitis vinifera L.) (VSE) and jabuticaba peel (Plinia cauliflora) (PPE) extracts were developed with potential application as food coatings. It was evaluated how the concentration of the extracts and their addition order in the polymeric matrix affect its properties. Samples with VSE presented a higher total phenolic content and also a more elastic behavior than samples with PPE. The addition order effect over viscosity was the opposite for the extracts, and for the samples with VSE a lower viscosity was obtained when the extract was added before gelatin. All samples were hydrophilic, a good result for application as coatings. Films with PPE were less soluble than chitosan/gelatin film, and CG5P sample was chosen as the most suitable for the desired application, due to its lower water vapor permeation value. The microbial permeation test showed that all samples avoid microorganism growth, extending shelf life of food. The results of this study revealed the extracts concentration was the main factor which influenced the studied parameters; however, their addition order had significant importance on rheological and barrier properties, the ones most influenced by the availability of extract compounds in the polymeric system. Unlabelled Image • Extracts of grape seed (VSE) and jabuticaba peel (PPE) are rich in phenolics. • Phenolics addition functionalized the properties of chitosan/gelatin mixtures. • Mixtures with VSE were more elastic and presented a higher phenolic content. • Higher extracts concentrations led to a reduction in initial viscosity of the samples. • Films properties were more influenced by extracts concentration than addition order. [ABSTRACT FROM AUTHOR]