Engineered urolithin A-laden functional polymer-lipid hybrid nanoparticles prevent cisplatin-induced proximal tubular injury in vitro.

Functional polymer-lipid hybrid nanoparticles (H-NPs) are a promising class of nanocarriers that combine the benefits of polymer and lipid nanoparticles, offering biocompatibility, structural stability, high loading capacity, and, most importantly, superior surface functionalization. Here, we report the synthesis and design of highly functional H-NPs with specificity toward the transferrin receptor (TfR), using a small molecule ligand, gambogic acid (GA). A fluorescence study revealed the molecular orientation of H-NPs, where the lipid-dense core is surrounded by a polymer exterior, functionalized with GA. Urolithin A, an immunomodulator and anti-inflammatory agent, served as a model drug-like compound to prepare H-NPs via traditional emulsion-based techniques, where H-NPs led to smaller particles (132 nm) and superior entrapment efficiencies (70 % at 10 % drug loading) compared to GA-conjugated polymeric nanoparticles (P-NPs) (157 nm and 52 % entrapment efficiency) and solid lipid nanoparticles (L-NPs) (186 nm and 29 % entrapment efficiency). H-NPs showed superior intracellular accumulation compared to individual NPs using human small intestinal epithelial (FHs 74) cells. The in vitro efficacy was demonstrated by flow cytometry analysis, in which UA-laden H-NPs showed excellent anti-inflammatory properties in cisplatin-induced injury in healthy human proximal tubular cell (HK2) model by decreasing the TLR4, NF-κß, and IL-ß expression. This preliminary work highlights the potential of H-NPs as a novel functional polymer-lipid drug delivery system, establishing the foundation for future research on its therapeutic potential in addressing chemotherapy-induced acute kidney injury in cancer patients.

Residual limb strength and functional performance measures in individuals with unilateral transtibial amputation.

BACKGROUND: Individuals with lower limb amputation exhibit lower residual limb strength compared to their sound limb. Deficits in residual limb knee flexion and extension strength may impact functional performance during tasks relevant to daily living. RESEARCH QUESTION: Does knee flexor and extensor strength in the residual limb impact functional outcome measures, such as walking energetics and performance metrics, in individuals with unilateral transtibial amputation? METHODS: Fourteen individuals with traumatic unilateral transtibial amputation were recruited for this observational study. Participants completed metabolic testing at three standardized speeds based on leg length, as well maximum isokinetic knee flexion and extension strength for both residual and sound limbs. Participants also completed a series of functional outcome tests, including a two-minute walk test, timed stair ascent test, and four-square step test. Walking energetics (metabolic cost, heart rate, and rating of perceived exertion) and performance metrics were compared to percent deficit of residual limb to sound limb knee flexion and extension muscle strength. A linear regression assessed significant relationships (p < 0.05). RESULTS: A significant relationship was observed between percent deficit of knee extension strength and heart rate (p = 0.024) at a fast walking speed. Additionally, percent deficit knee flexion strength related to rating of perceived exertion at slow and moderate walking speeds (p = 0.038, p = 0.024). Percent deficit knee extension strength related to two-minute walk time performance (p = 0.035) and percent deficit knee flexion strength related to timed stair ascent time (p = 0.025). SIGNIFICANCE: These findings suggest the importance of strength retention of the residual limb knee flexion and extension musculature to improve certain functional outcomes in individuals with unilateral transtibial amputation.

Social inequalities and nutritional disparities: the link between obesity and COVID-19.

OBJECTIVE: Cohort studies, clinical audits of patients with COVID-19 in hospital and routine primary care records provided evidence-based insights on the relationship between excess weigh, obesity and COVID-19. The purpose of this umbrella review is to highlight the relationship between nutritional quality and social inequalities related to CDNCD, obesity and SARS-CoV-2 infection. MATERIALS AND METHODS: Only articles published from 2008 to the present were included in the search to show an updated picture of the topic. The search for published studies was conducted in February 2021 in the scientific databases PubMed (MEDLINE). The terms used for the search were "COVID-19", "Obesity", "Disparities", "Nutritional inequalities", "Chronic degenerative non-communicable diseases" and "review" OR "systematic review" OR "meta-analysis" separated by the Boolean operator AND. RESULTS: 1874 reviews were found, but only 99 met the objective. Obese or dysmetabolic patients are those who had a worse course of disease following COVID-19. This data was observed not only for Chinese and Caucasians, but also and above all among Africans, African Americans, Latinos and indigenous people. Plausible mechanisms to explain the association between obesity and COVID-19 outcomes, included the role of excess adipose tissue on respiratory function, metabolic dysfunction, the cardiovascular system, enhanced inflammatory response and impaired response to infection. CONCLUSIONS: Today, chronic non-communicable degenerative diseases (CDNCDs) are responsible for 70% of public health expenditure, affecting 30% of the population (one or more chronic diseases). Unfortunately, given the health emergency due to SARS-CoV-2, infectious diseases are currently more at the center of attention. However, the spread of infectious communicable diseases and CDNCDs is facilitated in situations of social disparity. In fact, in the poorest countries there are the highest rates of malnutrition and there is a greater risk of contracting viral infections, as well as, paradoxically, a risk of comorbidity, due to access to cheaper food and qualitatively poor, with high caloric density.

Superomedial pedicle skin-reducing mastectomy in ptotic and large-sized breasts with two-stage reconstruction through transaxillary video-assisted technique: An effective surgical and anesthetic approach.

Introduction: Skin-reducing mastectomy has been applied to several surgical techniques in which subcutaneous mastectomy is associated with various types of skin reduction, with preservation of a lower dermal flap to reinforce the inferior lateral seat of an implant. The aim of the study is to present a case series of patients with pendulous/ptotic and/or large-sized breasts treated for breast cancer at the Breast Surgery Unit of Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale", Naples, Italy, with the superomedial pedicle skin-reducing mastectomy technique, two-stage reconstruction, and transaxillary video-assisted technique, when a postoperative radiotherapy was indicated. We verified its effectiveness by discussing its results, especially in patients who are candidates for postmastectomy radiotherapy. Materials and methods: A single-center retrospective study was performed between January 2020 and March 2021 on a prospectively filled database of conservative mastectomies. Of the 64 patients who underwent nipple/skin-sparing mastectomies in the mentioned period, 17 (mean age 46 years, range 30-62 years) were treated with superomedial pedicle skin-reducing mastectomy, with two-stage breast reconstruction through transaxillary video-assisted replacement expander with definitive prosthesis and contralateral symmetrization, selected for postmastectomy radiotherapy. Results: We had only three minor complications. No flap necrosis, no infections, no breast seromas, and no reconstructive failures were observed. During follow-up of the patients treated with video-assisted reconstruction, there were no cases of infection, hematoma, implant rupture, or suture dehiscence in the reconstructed breast. Discussion: Skin-reducing mastectomy with superomedial pedicle is a safe and reliable procedure to treat breast cancer in selected patients, i.e., those with pendulous/ptotic and or large-sized breasts. Particularly, in patients who undergo postmastectomy radiotherapy, the two-stage reconstruction with video-assisted transaxillary endoscopic approach can find its main indication, using incisions positioned far from the mammary region, offering numerous advantages.

Incorporation of 45S5 bioglass via sol-gel in ß-TCP scaffolds: Bioactivity and antimicrobial activity evaluation.

In this work, ß-TCP (ß-tricalcium phosphate) bioresorbable scaffolds were prepared by the gel casting method. Then, they were impregnated with a 45S5 bioglass sol gel solution to improve biocompatibility and promote bioactivity and antimicrobial activity. The ß-TCP scaffolds had an apparent porosity of 72%, and after the incorporation of the bioglass, this porosity was maintained. The elements of the bioglass were incorporated into ß-TCP matrix and there was a partial transformation from the ß-TCP phase to the α-TCP (α-tricalcium phosphate) phase, besides the formation of bioactive calcium and sodium­calcium silicates. The scaffolds ß-TCP with 45S5 bioglass incorporated (ß-TCP/45S5) did not show a reduction in their values of mechanical strength and Weibull modulus, despite the partial transformation to the α-TCP phase. Bioactivity, cell viability, and antimicrobial activity improved significantly for the ß-TCP/45S5 scaffold comparing to the scaffold without the bioglass. The mineralization of carbonated hydroxyapatite was verified in Simulated Body Fluid (SBF). The cell viability, evaluated by the reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide - MTT in MG63 cells, increased by 178%, and ß-TCP/45S5 scaffold also enhanced cell activity and osteoblast differentiation observed by means of total protein contend and alkaline phosphatase activity, respectively. The formation of growth inhibition zones was also observed in the disk diffusion assay for three tested microorganisms: Staphylococcus aureus, Escherichia coli and Candida albicans. To conclude, the vacuum impregnation method in 45S5 bioglass sol gel solution was effective in penetrating all the interconnected macroporosity of the scaffolds and covering the surface of the struts, which improved their biological properties in vitro, bioactivity and antibacterial activity, without reducing mechanical strength and porosity values. Thus, the ß-TCP/45S5 scaffolds are shown as potential candidates for use in tissue engineering, mainly in bone tissue regeneration and recovery.

A potential risk assessment tool to monitor pathogens circulation in coastal waters.

The present study reports data on a 20 months campaign monitoring enteric viruses (hepatitis A, norovirus, rotavirus, astrovirus, sapovirus, and aichivirus) and bacteria (Salmonella spp.) in seawater. The aim of this work was to assess the potential correlation among the presence of viruses/bacteria and different environmental factors like seasonality, water discharge sources (treated and untreated wastewater, mixed waters and raw water) as well as influence of the Italian lockdown measure against COVID-19 pandemic. Results showed different prevalence of the investigated viruses with values equal to 16 % for norovirus GI, 15.1 % for norovirus GII, followed by 13.8 % for astrovirus, and 13.3 % for sapovirus. Rotavirus was detected in the 8.4 % of samples and aichivirus was detected with the lowest prevalence of 3.5 %. Hepatitis A virus was never identified in the monitoring campaign. Salmonella spp. was detected with a prevalence of 36.6 %. Statistical analysis displayed a high correlation for the two noroviruses simultaneous detection (NGI and NGII) while a lower correlation was found for co-presence of noroviruses with astrovirus, sapovirus or Salmonella spp. A significant decrease of enteric pathogens in seawater was observed during the restrictions period. Results on seasonality highlighted a higher viral prevalence correlated to the wet season for all the pathogens but rotavirus and aichivirus, which instead showed an opposite trend and a higher incidence in the dry season. With respect to discharge typology, some viruses displayed a higher prevalence in treated waters (astrovirus, rotavirus, sapovirus and aichivirus) while the other investigated pathogens (noroviruses and Salmonella spp.) showed a higher prevalence in mixed waters. The main observations of this work were used to define a potential monitoring strategy that could be useful for sanitary Authorities to implement surveillance plans aimed at preventing possible sanitary outbreaks and/or environmental quality deterioration.

Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in Italy.

Conclusions: Our data reinforces the need to monitor the molecular epidemiology of CR A. baumannii and its associated antimicrobial resistance genes at national level. Background: Carbapenem-resistant (CR) Acinetobacter baumannii has been increasingly recognized as a major cause of health care-associated infections in critically ill patients and hospital outbreaks. Results: CR A. baumannii isolates assigned to international clonal lineage II (ICL II) and to ST78 clonal lineages were responsible for several epidemics in Italian hospitals during 2002-2018. Molecular analysis of carbapenem resistance showed the presence of OXA-58 CHDL in A. baumannii isolates assigned to ICL II and ST78 clonal lineage, which was replaced by OXA-23 CHDL in A. baumannii isolates assigned to ICL II since 2007 in several hospitals. CR A. baumannii was mainly responsible for respiratory tract infections and at a lesser extent for sepsis in intensive care unit patients. Methods: A narrative review of literature was conducted, searching PubMed database for articles on CR Acinetobacter spp. isolates from Italy published between January 2010 and December 2019.

Columbia spotted frogs (Rana luteiventris) have characteristic skin microbiota that may be shaped by cutaneous skin peptides and the environment.

Global amphibian declines due to the fungal pathogen Batrachochytrium dendrobatidis (Bd) have led to questions about how amphibians defend themselves against skin diseases. A total of two amphibian defense mechanisms are antimicrobial peptides (AMPs), a component of amphibian innate immune defense and symbiotic skin bacteria, which can act in synergy. We characterized components of these factors in four populations of Columbia spotted frogs (Rana luteiventris) to investigate their role in disease defense. We surveyed the ability of their AMPs to inhibit Bd, skin bacterial community composition, skin metabolite profiles and presence and intensity of Bd infection. We found that AMPs from R. luteiventris inhibited Bd in bioassays, but inhibition did not correlate with Bd intensity on frogs. R. luteiventris had two prevalent and abundant core bacteria: Rhizobacter and Chryseobacterium. Rhizobacter relative abundance was negatively correlated with AMP's ability to inhibit Bd, but was not associated with Bd status itself. There was no relationship between metabolites and Bd. Bacterial communities and Bd differ by location, which suggests a strong environmental influence. R. luteiventris are dominated by consistent core bacteria, but also house transient bacteria that are site specific. Our emergent hypothesis is that host control and environmental factors shape the microbiota on R. luteiventris.

The impact of scanning data measurements on the Acuros dose calculation algorithm configuration.

BACKGROUND: Many dose calculation algorithms for radiotherapy planning need to be configured for each clinical beam using pre-defined measurements. An optimization process adjusts the physical parameters able to estimate the energy released in the medium in any geometrical condition. This work investigates the impact of measured input data quality on the configuration of the type "c" Acuros-XB dose calculation algorithm in the Eclipse (Varian Medical Systems) treatment planning system. METHODS: Different datasets were acquired with the BeamScan water phantom (PTW) to configure 6 MV beams, for both flattened (6X) and flattening filter free mode (6FFF) for a Varian TrueBeam: (i) a correct dataset measured using a Semiflex-3D ion chamber, (ii) a set in missing lateral scatter conditions (MLS), (iii) a set with incorrect effective point of measurement (EPoM), (iv) sets acquired with PinPoint-3D chamber, DiodeP, microDiamond detectors. The Acuros-XB dose calculation algorithm (version 15.6) was configured using the reference dataset, the sets measured with the different detectors, with intentional errors, and using the representative beam data (RBD) made available by the vendor. The physical parameters obtained from each optimization process (spectrum, mean radial energy, electron contamination), were analyzed and compared. Calculated data were finally compared against the input and reference measurements. RESULTS: Concerning the physical parameters, the configurations presenting the largest differences were the MLS conditions (mean radial energy) and the incorrect EPoM (electron contamination). The calculation doses relative to the input data present low accuracy, with mean differences > 2% in some conditions. The PinPoint-3D ion chamber presented lower accuracy for the 6FFF beam. Regarding the RBD, calculations compared well with the input data used for the configuration, but not with the reference data. CONCLUSION: The MLS conditions and the incorrect setting of the EPoM lead to erroneous configurations and should be avoided. The choice of an appropriate detector is important. Whenever the representative beam data is used, a careful check under more clinical geometrical conditions is advised.

Short Report - Medical nutrition therapy for critically ill patients with COVID-19.

No Abstract Available.

Protective effect of sodium propionate in Aß1-42 -induced neurotoxicity and spinal cord trauma.

Sodium propionate (SP) is one of the main short chain fatty acids (SCFA) that can be produced naturally through host metabolic pathways. SP have been documented and include the reduction of pro-inflammatory mediators in an in vivo model of colitis. The aim of this study is to evaluate the neuroprotective effects of SP in reducing inflammatory process associated to neurological disorders. We performed both in vitro model of Alzheimer's disease, induced by oligomeric Aß1-42 stimulation, and in in vivo model of spinal cord injury (SCI) in which neuroinflammation plays a crucial role. For in vitro model, the human neuroblastoma SH-SY5Y cell line was first differentiated with retinoic acid (100 µM) for 24 h and then stimulated by oligomeric Aß1-42 (1 µg/ml) and treated with SP at 0.1- 1-10 µM concentrations for another 24 h. Instead, the in vivo model of SCI was induced by extradural compression of the spinal cord at T6-T8 levels, and animals were treated with SP (10-30-100 mg/kg o.s) 1 and 6 h after SCI. Our results demonstrated that both in in vitro neuroinflammatory model and in vivo model of SCI the treatment with SP significantly reduced NF-κB nuclear translocation and IκBα degradation, as well as decreases COX-2 and iNOS expressions evaluated by Western blot analysis. Moreover, we showed that SP treatment significantly ameliorated histopathology changes and improved motor recovery in a dose-dependent manner. In conclusion, our results demonstrated that SP possesses neuroprotective effects, suggesting it could represent a target for therapeutic intervention in neuroinflammatory disorders.

Near-infrared modulation by means of GeTe/SOI-based metamaterial.

Today, nanophotonics still lacks components for modulation that can be easily implementable in existing silicon-on-insulator (SOI) technology. Chalcogenide phase change materials (PCMs) are promising candidates for tuning in the near infrared: at the nanoscale, thin layers can provide enough contrast to control the optical response of a nanostructure. Moreover, all-dielectric metamaterials allow for resonant behavior without having ohmic losses in the telecom range. Here, a novel hybridization of a SOI-based metamaterial with PCM GeTe is experimentally investigated. A metamaterial based on Si nanorods, covered by a thin layer of GeTe, is designed and fabricated. Switching GeTe from amorphous to crystalline leads to a rather high resonance-governed reflection contrast at 1.55 µm. Additional confocal Raman imaging is done to differentiate the crystallized zones of the metamaterials' unit cell. The findings are in good agreement with numerical analysis and show good perspectives of all-dielectric tunable near-infrared nanophotonics.

Ankle-foot orthosis alignment affects running mechanics in individuals with lower limb injuries.

BACKGROUND: Individuals with severe lower extremity injuries often require ankle-foot orthoses to return to normal activities. Ankle-foot orthoses alignment is a key consideration during the clinical fitting process and may be particularly important during dynamic activities such as running. OBJECTIVE: To investigate how 3° changes in sagittal plane ankle-foot orthoses alignment affect running mechanics. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve participants with unilateral lower limb injury ran overground and lower extremity running mechanics were assessed. Participants wore their passive-dynamic ankle-foot orthoses in three alignments: clinically fit neutral, 3° plantarflexed from clinically fit neutral, and 3° dorsiflexed from clinically fit neutral. RESULTS: The 3° changes in sagittal alignment significantly influenced ankle mechanics during running. The plantarflexed alignment significantly decreased the peak ankle plantarflexor moment, peak knee extensor moment, and peak ankle and knee power absorption and generation compared to more dorsiflexed alignments. Alignment also altered footstrike angle, with dorsiflexed alignments associated with a more dorsiflexed footstrike pattern and plantarflexed alignments toward a more plantarflexed footstrike pattern. However, alignment did not influence loading rate. CONCLUSION: Small changes in ankle-foot orthoses alignment significantly altered running mechanics, including footstrike angle, and knee extensor moments. Understanding how ankle-foot orthoses design parameters affect running mechanics may aid the development of evidence-based prescription guidelines and improve function for ankle-foot orthoses users who perform high-impact activities. CLINICAL RELEVANCE: Understanding how ankle-foot orthoses alignment impacts biomechanics should be a consideration when fitting passive-dynamic devices for higher impact activities, such as running. Individual running styles, including footstrike patterns, may be affected by small changes in alignment.

Bevacizumab intravítreo en el tratamiento de las oclusiones venosas de la retina / Bevacizumab in the treatment of macular edema complicating retinal vein occlusions

INTRODUCCIÓN: Dentro de las vasculopatías retinianas, las oclusiones venosas de la retina (OVR) representan la segunda causa más frecuente de pérdida de visión luego de la retinopatía diabética. Se han descripto dos tipos diferentes de OVR: la oclusión de vena central de la retina (OVCR), y la oclusión de rama venosa retinal (ORVR). De acuerdo al compromiso oclusivo del lecho capilar de la retina, se las clasifica en isquémicas (o no perfundidas), y no isquémicas (perfundidas), presentando una patogénesis, diagnóstico, pronóstico y tratamiento diferente. Se ha demostrado que los niveles de factor de crecimiento vascular endotelial (VEGF) aumentan significativamente en las oclusiones venosas retinianas, lo que tiene como consecuencia una disfunción de la barrera hematorretinal y el aumento de la permeabilidad vascular, con el consecuente edema macular. La inyección intravítrea de bevacizumab, un anticuerpo monoclonal recombinante que actúa en forma directa contra cualquier forma activa de VEGF, ha demostrado ser efectiva para reducir el espesor macular y mejorar la agudeza visual en el tratamiento de OVR. OBJETIVO: Evaluar los cambios en la agudeza visual y en los espesores maculares de pacientes con oclusiones venosas retinianas tratados con inyecciones intravítreas de bevacizumab. Pacientes y métodos: Se evaluaron retrospectivamente 39 pacientes con diagnóstico de oclusión venosa retiniana (OVR) complicada de edema macular y tratados mediante inyección intravítrea de 1,25 mg/0,05 ml bevacizumab (Avastin®, Roche Diagnostic GmbH, Manheim, Alemania), con un seguimiento mínimo de 18 meses. La agudeza visual se evaluó mediante tabla de Snellen y se convirtió en unidades LogMAR. El espesor macular se evaluó mediante tomografía de coherencia óptica (OCT). Según la presentación clínica se las clasificó en: 1. Oclusión de rama (ORVR), incluyendo las oclusiones hemisféricas y 2. Oclusión de vena central (OVCR), incluyendo oclusión venosa hemicentral. A su vez, mediante angiografía fluoresceínica se las clasificó en oclusiones predominántemente isquémicas, y predominántemente no isquémicas. Las variables cuantitativas se analizaron mediante medidas de tendencia central, dispersión y forma. Los cambios en la agudeza visual se calcularon utilizando la prueba de Wilcoxon. Las diferencias entre variables continuas fueron calculadas mediante la prueba T de Student para variables paramétricas, y Mann Whitney para variables no paramétricas. RESULTADOS: La edad promedio fue de 66,8 años (DE: 13,65; rango= 31-92 años). El 55% de los casos estudiados fueron OVCR y el 37,5% ORVR. La media del total de inyecciones durante los 18 meses de seguimiento fue de 4,11±1,61 (rango= 1 a 6). La terapia con láser de rescate se realizó en 10 (25%) pacientes. Todos los pacientes que debieron ser tratados con láser tuvieron una AV inferior a 1 décima al final del seguimiento. La agudeza visual promedio al inicio del tratamiento fue de 1,092 con una desviación estándar (DE) de 0,36, con un rango de 0,10 y 1,60. Tras el inicio del tratamiento, todos los grupos de pacientes logran un incremento significativo en la AV (P= <0,0001). A los 18 meses de tratamiento la agudeza visual promedio fue de 0,739 con una DE de 0,45 con un rango de entre 0,00 y 1,50. La agudeza visual media de los pacientes con OVCR antes del tratamiento fue de 1,09 (DE: 0,35; rango= máxima 0,50 y mínima 1,60), y a los 18 meses de tratamiento de 0,87 (DE: 0,73; rango= 0,20 a 1,50). En cambio, los pacientes con ORVR antes del tratamiento presentaron una media de 1,10 (DE: 0,31; rango= máxima de 0,40 y mínima de 1,6), y luego del tratamiento una media de 0,53 (DE: 0,38; rango= máxima 0,1 y mínima 1,2). El 54,5% de los casos fue de predominio isquémico o mixtos, y el 43,5% fue a predominio edematosos al inicio del tratamiento. La agudeza visual media de los pacientes con tipo edematoso fue de 0,93 (DE: 0,34; rango= máxima 0,10 y mínima 1,40), mientras que los pacientes con patología isquémica presentaron una media de 1,25 (DE: 0,32; rango= máxima de 0,40 y mínima de 1,6). Ambos grupos respondieron en forma significativa al tratamiento (p< 0.05). Sin embargo, los pacientes con predominio edematoso lograron una mejoría mayor que aquellos con predominio isquémico. (P=0.0054) La agudeza visual media de los pacientes con predominio edematoso a los 18 meses del tratamiento fue de 0,50 (DE: 0,44; rango= máxima 0,0 y mínima 1,40), mientras que los pacientes con predominio isquémico presentaron una media de 0,97 (DE: 0,35; rango= máxima 0,20 y mínima 1,4). La media de los espesores maculares previo al inicio del tratamiento fue de 654.19 ± 272.05 micras (rango= 215 a 1497 micras), mientras que la media luego del tratamiento fue de 449 ± 247,62 micras (rango= 140 a 1005 micras) (p=0,0009). No hubo efectos colaterales ni complicaciones locales ni sistémicas atribuibles a la inyección de bevacizumab durante el seguimiento. CONCLUSIÓN: El bevacizumab fue eficaz en el tratamiento del edema macular secundario a OVR. La respuesta terapéutica fue mayor en las ORVR. En nuestra serie no hubo complicaciones oculares ni sistémicas vinculadas al tratamiento. (AU)

INTRODUCTION: Within the retinal vascular disease,retinal venous occlusion (RVO) represents the second most common cause of vision loss after diabetic retinopathy. In turn, it is estimated that the RVO affects approximately 1.6% of people worldwide. It has been described two different types of RVO: the central retinal vein occlusion (CRVO), which includes the hemicentral retinal vein occlusion (HCRVO), and the branch retinal vein occlusion (BRVO), which includes Major BRVO (occlusion of a retinal vein that drains one of the quadrants or more), Minor BRVO (occlusion of a retinal vein that drains less than a quadrant) and Hemispheric retinal vein occlusions (half or more of the retina). According to the occlusive pattern of the retinal capillary bed, this disease is classified as ischemic (or non perfused); when the areas of noncapillary perfusion, seen under fluorescein angiography, have an extension of more than 10 disc diameters; and non-ischemic (o perfused), presenting a pathogenesis, diagnosis, prognosis and different treatment. Non-ischemic form is generally more benign, with a less dramatic visual impairment, a greater chance of spontaneous recovery, a better treatment response, and generally has no risk of neovascularization. Instead; ischemic form is much more severe, causing a more dramatic visual acuity decline, with little chance of clinical improvement, an increased risk of blindness and an increased risk of neovascularization. Although the physiopathogenesis of OVR is not accurately known, it is suggested that the thickening and stiffness of arteries and arterioles caused by arteriosclerosis leads to compression of the retinal veins at the sites where adventitia is shared with arteries (in its intraneural route to the optic nerve and the arteriovenous crossings), leading eventually to a turbulent blood flow, damage to endothelial cells, thrombus formation and eventual vein occlusion. This theory is supported by studies showing pathological structural changes in veins and arteries of patients with VO. Moreover, other factors related to venous deregulation, such as inadequate vasoconstriction and increased vascular permeability, could also play an important role in the retinal venous occlusive phenomena. In some patients, especially young people and adults under 50 years old, inflammatory disorders and hypercoagulable states may contribute to the hysiopathogenesis of the RVO. It has been shown that the presence of vascular endothelial growth factor (VEGF) increased significantly the chances to develop retinal vein occlusions. The result is a blood­retinal barrier dysfunction and an increased vascular permeability, with consequent macular edema. It has also been reported that VEGF plays an important role in the pathogenesis of macular edema in both ORV and CRVO.10 While there is insufficient level 1 evidence to support OVR treatment, multiple therapeutic possibilities have been described, such as anticoagulation, intravitreal fibrinolysis, hemodilution, laser photocoagulation, laser-induced anastomosis, radial optical neurotomy, adventiciotomía, intravitreal injection of triamcinolone acetonide, intravitreal injection of dexamethasone, and injection intravitreal antiangiogenic monoclonal antibodies, such as ranibizumab, bevacizumab, and aflibercept, alone or associated with photocoagulation, have shown efficacy and variables complications rates. Intravitreal injection of bevacizumab, a recombinant monoclonal antibody that acts directly against any active form of VEGF, has been shown to be effective in reducing macular thickness and improving visual acuity in the treatment of OVR. However, the need for multiple injections has been reported since the effects of intravitreal bevacizumab (as well as the other antiangiogenics) are short-lived. On one hand, Bevacizumab has the disadvantage that it is administered off-label; in addition each dose must be extracted from a vial for oncological use, which represents a risk of contamination if strictly rules of asepsis are not taken. On the other hand, the cost of each dose is lower than that of other products (ranibizumab, aflibercept) already approved for intraocular use. This allows that more patients have access to a prolonged treatment in underdeveloped or developing countries, such as Argentina. PURPOSE: To evaluate changes in visual acuity and macular thickness after intravitreal bevacizumab for the treatment of macular edema in patients with retinal vein occlusions (RVO). PATIENS AND METHODS: 39 consecutive patients with macular edema complicating RVO and treated with intravitreal injections of bevacizumab 1.25 mg/0.05 ml alone or associated with scattered peripheral laser photocoagulation, with a minimun follow-up of 18 months, were evaluated. Snellen visual acuity in LogMar units and macular thinckness measured by optical coherence tomography (OCT) were the end points. According to clinical and fluorescein angiographic presentation RVO were classified in branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO), and in non ischemic and ischemic. Wilcoxon test for paired variables, Mann Whitney for independant variables, and Student test for continuous variables, were used for statistical analysis. RESULTS: With a mean age of 66.8 years (SD: 13.65; range= 31-92 years), 62.5% of cases were CRVO and 37.5% BRVO. Mean number of injections was 4.11±161 (range= 1-6). Laser was performed in 25% of patients that did not respond to bevacizumab. At 18 months of follow-up, improvement of visual acuity and macular thickness was statistically significant (p=0.0001 and p=0.0009 respectively). BRVO showed better response to treatment than CRVO. Best visual results were obtained at first month (median= 1.00 P25= 0.5 P75= 1.30) and at 9 month (median= 0.8 P25= 0.5 P75= 1.20) after first injection, but no further improvement was observed beyond 9 months of treatment (p=0.84). No significant visual and macular thickness differences were obtained between patients treated with bevacizumab alone (p=0.116) and bevacizumab and laser (p=0.846). No ocular or systemic attributable-to-treatment side effects were observed. CONCLUSIONS: Bevacizumab was effective in improving visual acuity and reducing macular thinckness in patients with macular edema complicating RVO, especially in BRVO. No ocular or systemic complications were observed during follow-up. (AU)

Risk Differences Between Prediabetes And Diabetes According To Breast Cancer Molecular Subtypes.

Hyperglycemia and hyperinsulinemia may play a role in breast carcinogenesis and prediabetes and diabetes have been associated with increased breast cancer (BC) risk. However, whether BC molecular subtypes may modify these associations is less clear. We therefore investigated these associations in all cases and by BC molecular subtypes among women living in Southern Italy. Cases were 557 patients with non-metastatic incident BC and controls were 592 outpatients enrolled during the same period as cases and in the same hospital for skin-related non-malignant conditions. Adjusted multivariate logistic regression models were built to assess the risks of developing BC in the presence of prediabetes or diabetes. The analyses were repeated by strata of BC molecular subtypes: Luminal A, Luminal B, HER2+, and Triple Negative (TN). Prediabetes and diabetes were significantly associated with higher BC incidence after controlling for known risk factors (OR = 1.94, 95% CI 1.32-2.87 and OR = 2.46, 95% CI 1.38-4.37, respectively). Similar results were seen in Luminal A and B while in the TN subtype only prediabetes was associated with BC (OR = 2.43, 95% CI 1.11-5.32). Among HER2+ patients, only diabetes was significantly associated with BC risk (OR = 3.04, 95% CI 1.24-7.47). Furthermore, when postmenopausal HER2+ was split into hormone receptor positive versus negative, the association with diabetes remained significant only in the former (OR = 5.13, 95% CI 1.53-17.22). These results suggest that prediabetes and diabetes are strongly associated with BC incidence and that these metabolic conditions may be more relevant in the presence of breast cancer molecular subtypes with positive hormone receptors. J. Cell. Physiol. 232: 1144-1150, 2017. © 2016 Wiley Periodicals, Inc.

Painful bone metastasis in elderly treated with radiation therapy: Single- or multiple-fraction regimen? A multicentre retrospective observational analysis.

BACKGROUND: Bone metastases are a frequent complication of advanced oncologic disease. Pain associated to bone metastasis is a major cause of morbidity in cancer patients, especially in elderly. AIMS: The aim of this multicentric retrospective observational study is to evaluate the efficacy of different schedules of radiation therapy in elderly patients in terms of pain relief. METHODS: 206 patients over the age of 60 were enrolled in 1 year time for a multicentre retrospective observational study. Patients were treated with palliative purposes for painful bone metastases. RESULTS: Pain intensity difference (PID) was found in 72% of patients. Reported PID was statistically significant for p < 0.01. Pain intensity measured by a point numeric rating scale was statistically significant reduced for p < 0.05 by one-fraction regimen compared to other two regimens. DISCUSSION: In recent years, numerous studies have evaluated the most appropriate regimen of fractionation in individual cases, despite this, a consensus about the best schedule is still debated. CONCLUSIONS: On our analysis, single-fractionation scheme (8 Gy) confirmed to be statistical significant effective in providing pain reduction due to bone metastases. Radiation therapy provides significant pain relief of symptomatic bone metastases, but appropriate radiotherapy scheduled is needed in order to get significant response to treatment. Multidisciplinary approach is warranted to value the balance between the therapeutic objectives and the patient quality of life.

PPAR-α Modulates the Anti-Inflammatory Effect of Melatonin in the Secondary Events of Spinal Cord Injury.

Melatonin is the principal secretory product of the pineal gland, and its role as an immunomodulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and reduces the development of inflammation and tissue injury events associated with spinal cord trauma. Previous results suggest that peroxisome proliferator-activated receptor α (PPAR-α), a nuclear receptor protein that functions as a transcription factor activated by fatty acids, plays a role in control of secondary inflammatory process associated with spinal cord injury (SCI).With the aim to characterize the role of PPAR-α in melatonin-mediated anti-inflammatory activity, we tested the efficacy of melatonin (30 mg/kg) in an experimental model of spinal cord trauma, induced in mice, by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy, and comparing mice lacking PPAR-α (PPAR-α KO) with wild-type (WT) mice.The results obtained indicate that melatonin-mediated anti-inflammatory activity is weakened in PPAR-α KO mice, as compared to WT controls. In particular, melatonin was less effective in PPAR-α KO, compared to WT mice, as evaluated by inhibition of the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, pro-inflammatory cytokine expression, nuclear factor κB (NF-κB) activation, and inducible nitric oxide synthase (iNOS) expression. This study indicates that PPAR-α can contribute to the anti-inflammatory activity of melatonin in SCI.