Impact of abnormal uterine bleeding care in premenopausal patients prior to endometrial malignancy diagnosis.

Background: Literature evaluating the management of abnormal uterine bleeding in premenopausal patients prior to endometrial malignancy diagnosis is lacking. Objective: To evaluate predictors and consequences of inadequate evaluation and management of abnormal uterine bleeding and time to endometrial sampling in premenopausal patients prior to endometrial malignancy diagnosis.Study Design.This was a retrospective cohort study of premenopausal individuals with endometrioid endometrial cancer or atypical hyperplasia at a single institution from 2015 to 2020.. Complete noninvasive management encompassed pelvic exam, ultrasound, and progestin treatment before or in conjunction with the endometrial sampling of diagnosis. Multivariable logistic and ordinal odds models were used to evaluate predictors and outcomes. Results: 152 subjects were included, 80.3 % with cancer and 19.7 % with atypical hyperplasia. The majority of patients had anovulatory bleeding, obesityand recent health care. Only 20.4 % had complete nonvinvasive management, and only 12.5 % had complete noninvasive management or endometrial sampling within 2 months of presentation with abnormal bleeding. Class III obesity reduced the likelihood of complete assessment and increased time to sampling, while age 45 and up and parity reduced time to sampling. Most patients had partial workup but no progestin treatment and long intervals before endometrial sampling after presentation to a provider with abnormal bleeding. Incomplete workup correlated to worse cancer grade and stage. Conclusion: Despite high clinical risk and health care contact, most patients had insufficient gynecologic management preceding a diagnosis of endometrial malignancy. Inadequate care correlated to worse oncologic outcomes and demonstrates missed opportunities for early detection and prevention of endometrial cancer.

Advances in surface modifications of the silicone breast implant and impact on its biocompatibility and biointegration.

Silicone breast implants are commonly used for cosmetic and oncologic surgical indications owing to their inertness and being nontoxic. However, complications including capsular contracture and anaplastic large cell lymphoma have been associated with certain breast implant surfaces over time. Novel implant surfaces and modifications of existing ones can directly impact cell-surface interactions and enhance biocompatibility and integration. The extent of foreign body response induced by breast implants influence implant success and integration into the body. This review highlights recent advances in breast implant surface technologies including modifications of implant surface topography and chemistry and effects on protein adsorption, and cell adhesion. A comprehensive online literature search was performed for relevant articles using the following keywords silicone breast implants, foreign body response, cell adhesion, protein adsorption, and cell-surface interaction. Properties of silicone breast implants impacting cell-material interactions including surface roughness, wettability, and stiffness, are discussed. Recent studies highlighting both silicone implant surface activation strategies and modifications to enhance biocompatibility in order to prevent capsular contracture formation and development of anaplastic large cell lymphoma are presented. Overall, breast implant surface modifications are being extensively investigated in order to improve implant biocompatibility to cater for increased demand for both cosmetic and oncologic surgeries.

The efficacy of neuro-optometric visual rehabilitation therapy in patients with visual snow syndrome.

Objective: This study intends to evaluate the feasibility of Neuro-Optometric Rehabilitation Therapy (NORT) to treat Visual Snow Syndrome (VSS). This pilot study utilized the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) to assess quality of life (QOL) before and after treatment. Methods: Twenty-one participants were recruited as successive intake patients diagnosed with VSS at the clinics of Dr. Terry Tsang Optometry, Inc and Neuro-Vision Associates of North Texas. Participants completed the NEI Visual Function Questionnaire 25-2000 edition and performed NORT, conducted by a neuro-optometrist or a qualified vision therapist. The NEI-VFQ-25 was administered before, at 6 weeks, and at 12 weeks of NORT to evaluate the effects of treatment on patient QOL. Results: The participants demonstrated an improvement in QOL composite and subscale scores after 6 and 12 weeks of NORT treatment. The NEI-VFQ-25 composite scores from the pre-test (M = 68, SD = 18) and at 6 weeks of treatment (M = 75, SD = 17) indicate an improvement in QOL [t (20) = 4.0, p = 0.0007]. The NEI-VFQ-25 composite scores from pretest to 12 weeks of treatment showed further improvements. This trend of improvement on NEI-VFQ-25 composite scores continued into the 12th week (M = 77, SD = 17) of treatment [t (20) = 4.5, p = 0.0002]. The subscales of general vision, distance activities, near activities, social functioning, mental health, role difficulties and dependency also showed improvement. Conclusion: Our results suggest that patients with VSS experience improvement in QOL in as little as 6 weeks, with further improvement by 12 weeks of NORT. This suggests NORT is an effective treatment option for managing the condition and improving QOL in patients with VSS, although a reduction in specific symptoms has yet to be demonstrated. This study provides justification that NORT warrants further investigation on VSS symptom reduction.

Chitosan nanoparticles for combined drug delivery and magnetic hyperthermia: From preparation to in vitro studies.

Chitosan nanoparticles (CSNPs) ionically crosslinked with tripolyphosphate salts (TPP) were employed as nanocarriers in combined drug delivery and magnetic hyperthermia (MH) therapy. To that aim, three different ferrofluid concentrations and a constant 5-fluorouracil (5-FU) concentration were efficiently encapsulated to yield magnetic CSNPs with core-shell morphology. In vitro experiments using normal cells, fibroblasts (FHB) and cancer cells, human glioblastoma A-172, showed that CSNPs presented a dose-dependent cytotoxicity and that they were successfully uptaken into both cell lines. The application of a MH treatment in A-172 cells resulted in a cell viability of 67-75% whereas no significant reduction of cell viability was observed for FHB. However, the A-172 cells showed re-growth populations 4h after the application of the MH treatment when CSNPs were loaded only with ferrofluid. Finally, a combined effect of MH and 5-FU release was observed with the application of a second MH treatment for CSNPs exhibiting a lower amount of released 5-FU. This result demonstrates the potential of CSNPs for the improvement of MH therapies.

Composite Chitosan/Agarose Ferrogels for Potential Applications in Magnetic Hyperthermia.

Composite ferrogels were obtained by encapsulation of magnetic nanoparticles at two different concentrations (2.0 and 5.0 % w/v) within mixed agarose/chitosan hydrogels having different concentrations of agarose (1.0, 1.5 and 2.0% (w/v)) and a fixed concentration of chitosan (0.5% (w/v)). The morphological characterization carried out by scanning electron microscopy showed that dried composite ferrogels present pore sizes in the micrometer range. Thermogravimetric measurements showed that ferrogels present higher degradation temperatures than blank chitosan/agarose hydrogels without magnetic nanoparticles. In addition, measurements of the elastic moduli of the composite ferrogels evidenced that the presence of magnetic nanoparticles in the starting aqueous solutions prevents to some extent the agarose gelation achieved by simply cooling chitosan/agarose aqueous solutions. Finally, it is shown that composite chitosan/agarose ferrogels are able to heat in response to the application of an alternating magnetic field so that they can be considered as potential biomaterials to be employed in magnetic hyperthermia treatments.

Chitosan/agarose hydrogels: cooperative properties and microfluidic preparation.

The preparation of composite biopolymer hydrogels offers the capability to produce biocompatible and biodegradable materials with cooperative properties. In this paper, two natural polymers, namely, chitosan and agarose were employed to prepare composite hydrogels with dual pH and temperature properties. The elastic modulus of the composite hydrogels increased with agarose concentration reaching the value of 1 kPa for the chitosan/agarose gel with a 2% (w/v) concentration of agarose. In addition, composite gels exhibited a higher stability in acidic aqueous solutions, in comparison with agarose gels. The drug release properties of the composite hydrogels were tested by loading a model anticancer drug, 5-Fluorouracil, in the hydrogel interior. At pH=7.4, the cumulative release of 5-FU was ∼ 50% within 96 h and decreased to ∼ 33% at pH = 5.2, which was attributed to the different solubility of 5-FU as a function of pH. The preparation of composite microgels with controllable dimensions in the range from 42 to 18 µm and with narrow size distribution (polidispersity not exceeding 1.5%) was achieved by the microfluidic emulsification of an aqueous mixture of chitosan and agarose and subsequent gelation of the precursor droplets by cooling.

Magnetic core-shell chitosan nanoparticles: rheological characterization and hyperthermia application.

Stabilized magnetic nanoparticles are the subject of intense research for targeting applications and this work deals with the design, preparation and application of specific core-shell nanoparticles based on ionic crosslinked chitosan. The nanometric size of the materials was demonstrated by dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM) that also proved an increase of the size of chitosan nanoparticles (NPs) with the magnetite content. Steady oscillatory rheology measurements revealed a gel-like behavior of aqueous dispersions of chitosan NPs with concentrations ranging from 0.5% to 2.0% (w/v). The cytotoxicity of all the materials synthesized was analyzed in human fibroblasts cultures using the Alamar Blue and lactate dehydrogenase (LDH) assays. The measured specific power absorption under alternating magnetic fields (f = 580 kHz, H = 24 kA/m) indicated that magnetic core-shell chitosan NPs can be useful as remotely driven heaters for magnetic hyperthermia.

EmrA1 membrane fusion protein of Francisella tularensis LVS is required for resistance to oxidative stress, intramacrophage survival and virulence in mice.

Francisella tularensis is a category A biodefence agent that causes a fatal human disease known as tularaemia. The pathogenicity of F. tularensis depends on its ability to persist inside host immune cells primarily by resisting an attack from host-generated reactive oxygen and nitrogen species (ROS/RNS). Based on the ability of F. tularensis to resist high ROS/RNS levels, we have hypothesized that additional unknown factors act in conjunction with known antioxidant defences to render ROS resistance. By screening a transposon insertion library of F. tularensis LVS in the presence of hydrogen peroxide, we have identified an oxidant-sensitive mutant in putative EmrA1 (FTL_0687) secretion protein. The results demonstrate that the emrA1 mutant is highly sensitive to oxidants and several antimicrobial agents, and exhibits diminished intramacrophage growth that can be restored to wild-type F. tularensis LVS levels by either transcomplementation, inhibition of ROS generation or infection in NADPH oxidase deficient (gp91Phox(-/-)) macrophages. The emrA1 mutant is attenuated for virulence, which is restored by infection in gp91Phox(-/-) mice. Further, EmrA1 contributes to oxidative stress resistance by affecting secretion of Francisella antioxidant enzymes SodB and KatG. This study exposes unique links between transporter activity and the antioxidant defence mechanisms of F. tularensis.

Identification of a novel Francisella tularensis factor required for intramacrophage survival and subversion of innate immune response.

Francisella tularensis, the causative agent of tularemia, is one of the deadliest agents of biological warfare and bioterrorism. Extremely high virulence of this bacterium is associated with its ability to dampen or subvert host innate immune response. The objectives of this study were to identify factors and understand the mechanisms of host innate immune evasion by F. tularensis. We identified and explored the pathogenic role of a mutant interrupted at gene locus FTL_0325, which encodes an OmpA-like protein. Our results establish a pathogenic role of FTL_0325 and its ortholog FTT0831c in the virulent F. tularensis SchuS4 strain in intramacrophage survival and suppression of proinflammatory cytokine responses. This study provides mechanistic evidence that the suppressive effects on innate immune responses are due specifically to these proteins and that FTL_0325 and FTT0831c mediate immune subversion by interfering with NF-κB signaling. Furthermore, FTT0831c inhibits NF-κB activity primarily by preventing the nuclear translocation of p65 subunit. Collectively, this study reports a novel F. tularensis factor that is required for innate immune subversion caused by this deadly bacterium.

Influence of iron oxide nanoparticles on the rheological properties of hybrid chitosan ferrogels.

Magnetite nanoparticles have been successfully synthesized in the presence of chitosan using an in situ coprecipitation method in alkali media. This method allows obtaining chitosan ferrogels due to the simultaneous gelation of chitosan. The chitosan concentration has been varied and its effects on the particle synthesis investigated. It has been demonstrated that high chitosan concentrations prevents the formation of magnetite due to the slow diffusion of the alkali species through the viscous medium provided by chitosan, instead iron hydroxides are formed. The presence of magnetite nanoparticles increases the elastic modulus which results in a reinforcement of the chitosan ferrogels. This effect is counterbalanced by the disruption of hydrogen bonding responsible for the formation of chitosan hydrogels in alkali media.