Sustained Delivery of Olopatadine from Vitamin-E Loaded Contact Lenses.

Purpose: Topical antihistamines, such as olopatadine hydrochloride, an H1 receptor antagonist, are commonly prescribed for treating allergic conjunctivitis. Drug delivery via eye drops has many deficiencies including a short residence time due to tear drainage via the nasolacrimal duct, which results in a low bioavailability and potential for side effects. These deficiencies could be mitigated by a drug-eluting contact lens such as the recently approved ACUVUE® THERAVISION™ WITH KETOTIFEN which is a daily disposable etafilcon, a drug-eluting contact lens with ketotifen (19 µg per lens). Here, we investigate the feasibility of designing a drug-eluting lens with sustained release of olopatadine for treating allergies using an extended wear lens. Methods: Nanobarrier depots composed of vitamin-E (VE) are formed through direct entrapment by ethanol-driven swelling. The drug-loaded lenses are characterized for transparency and water content. In vitro release is measured under sink conditions and fitted to a diffusion control release model to determine diffusivity and partition coefficient. Results: In vitro studies indicate that ACUVUE OASYS® and ACUVUE TruEye™ lenses loaded with ∼0.3 g of VE/g of hydrogel effectively prolong olopatadine dynamics by 7-fold and 375-fold, respectively. Incorporation of VE into the lenses retains visible light transmission and other properties. Conclusion: The VE incorporation in commercial lenses significantly increases the release duration offering the possibility of antiallergy extended wear lenses.

Treatment of Equine Tarsus Long Medial Collateral Ligament Desmitis with Allogenic Synovial Membrane Mesenchymal Stem/Stromal Cells Enhanced by Umbilical Cord Mesenchymal Stem/Stromal Cell-Derived Conditioned Medium: Proof of Concept.

Horses are high-performance athletes prone to sportive injuries such as tendonitis and desmitis. The formation of fibrous tissue in tendon repair remains a challenge to overcome. This impels regenerative medicine to develop innovative therapies that enhance regeneration, retrieving original tissue properties. Multipotent Mesenchymal Stem/Stromal Cells (MSCs) have been successfully used to develop therapeutic products, as they secrete a variety of bioactive molecules that play a pivotal role in tissue regeneration. These factors are released in culture media for producing a conditioned medium (CM). The aforementioned assumptions led to the formulation of equine synovial membrane MSCs (eSM-MSCs)-the cellular pool that naturally regenerates joint tissue-combined with a medium enriched in immunomodulatory factors (among other bioactive factors) produced by umbilical cord stroma-derived MSCs (eUC-MSCs) that naturally contribute to suppressing the immune rejection in the maternal-fetal barrier. A description of an equine sport horse diagnosed with acute tarsocrural desmitis and treated with this formulation is presented. Ultrasonographic ligament recovery occurred in a reduced time frame, reducing stoppage time and allowing for the horse's return to unrestricted competition after the completion of a physical rehabilitation program. This study focused on the description of the therapeutic formulation and potential in an equine desmitis treatment using the cells themselves and their secretomes.

Nelson syndrome and perinatal challenges: A case report and systematic review of the literature.

Nelson syndrome is a rare and potentially life-threatening complication of treatment with total bilateral adrenalectomy for women with Cushing disease. A successful term pregnancy following fertility treatment in a patient with Nelson syndrome is presented. Our study provides guidance in the prenatal and intrapartum management of this condition. A case report and a systematic review of 14 papers describing 50 pregnancies are presented. An electronic database search included Medline (1946 to September 2022), Embase (1980 to September 2022), Cochrane Library, and UKOSS. A small number of pregnancies in women with Nelson syndrome are reported in literature, but there are no guidelines. Some authors detail the prenatal care provided to their patients. Four studies report prenatal monitoring with visual field checks and two report monitoring with X-rays. Five studies report the use of parenteral hydrocortisone at the time of delivery. Where described, women delivered appropriately grown newborns at term, with timing and mode of delivery dictated by obstetric indications. Preconception counseling and optimization of maternal health status improve pregnancy outcomes in women with Nelson syndrome. Multidisciplinary review in a combined obstetric-endocrine prenatal clinic is ideal. Awareness about potential complications during pregnancy and the postnatal period is crucial in providing optimal care to the mother and baby.

Allogenic Synovia-Derived Mesenchymal Stem Cells for Treatment of Equine Tendinopathies and Desmopathies-Proof of Concept.

Tendon and ligament injuries are frequent in sport horses and humans, and such injuries represent a significant therapeutic challenge. Tissue regeneration and function recovery are the paramount goals of tendon and ligament lesion management. Nowadays, several regenerative treatments are being developed, based on the use of stem cell and stem cell-based therapies. In the present study, the preparation of equine synovial membrane mesenchymal stem cells (eSM-MSCs) is described for clinical use, collection, transport, isolation, differentiation, characterization, and application. These cells are fibroblast-like and grow in clusters. They retain osteogenic, chondrogenic, and adipogenic differentiation potential. We present 16 clinical cases of tendonitis and desmitis, treated with allogenic eSM-MSCs and autologous serum, and we also include their evaluation, treatment, and follow-up. The concerns associated with the use of autologous serum as a vehicle are related to a reduced immunogenic response after the administration of this therapeutic combination, as well as the pro-regenerative effects from the growth factors and immunoglobulins that are part of its constitution. Most of the cases (14/16) healed in 30 days and presented good outcomes. Treatment of tendon and ligament lesions with a mixture of eSM-MSCs and autologous serum appears to be a promising clinical option for this category of lesions in equine patients.

Ansiedade pré-operatória e mindfulness: Relatório final de estágio / Preoperative anxiety and mindfulness: Final internship report

Este relatório apresenta-se como trabalho final de Mestrado em Enfermagem de Saúde Mental e Psiquiátrica, do Instituto Politécnico de Leiria. Constitui-se em duas partes de desenvolvimento, referentes às competências adquiridas e desenvolvidas enquanto mestranda desta área. Na primeira parte analisam-se as atividades desenvolvidas durante os ensinos clínicos e estágio realizados, recorrendo a uma metodologia descritiva, analítica e critico-reflexiva, incorporando as experiências vivenciadas e as estratégias aplicadas em cada momento, que permitiram o desenvolvimento das competências previstas para o Enfermeiro Especialista, quer as comuns a todos estes profissionais, quer as específicas para os profissionais especialistas da área da Saúde Mental e Psiquiátrica, definidas pela Ordem dos Enfermeiros. Na segunda parte deste relatório apresenta-se o processo de desenvolvimento de um Projeto de Melhoria Contínua da Qualidade dos Cuidados de Enfermagem em contexto de internamento hospitalar cirúrgico, com componentes científica e reflexiva, resultantes de um processo de investigação-ação sobre o foco de ansiedade pré-operatória. O referencial teórico emerge da literatura disponível, e o prático da experiência da equipa e o seu parecer referente ao projeto. Esta fase do relatório permite evidenciar a transladação para o contexto prático dos conhecimentos adquiridos no contexto académico, contribuindo assim para a melhoria contínua fundamentada dos cuidados prestados. O desenvolvimento de aprendizagens e competências dos enfermeiros e da própria ciência de enfermagem deve visar as necessidades de cuidados de saúde das pessoas e das populações, e a formação progressiva, contínua e diferenciada dos profissionais deve procurar a excelência dos cuidados, de formas criativas e que simultaneamente satisfaçam o cliente e as instituições prestadoras de cuidados e reguladoras desses. Acredita-se que a formação espelhada neste relatório é congruente com esse princípio e que se traduzirá na melhoria dos cuidados prestados enquanto enfermeira, tendo também contribuído para o desenvolvimento pessoal.

This report is presented as the final work of the Master's Degree in Mental Health and Psychiatric Nursing of the Polytechnic Institute of Leiria. It is divided into two developmental parts, which refer to the competencies acquired and developed as a master's student in this area. The first part analyses the activities developed during the clinical training and internship, using a descriptive, analytical and critical-reflective methodology, incorporating the experiences and the strategies applied at each moment, which allowed developing the competencies expected for the Nurse Specialist, both those common to all these professionals and the specific competencies defined by the Ordem dos Enfermeiros for Mental Health and Psychiatric Specialists. The second part of this report presents the development process of a Continuous Quality Improvement Project of Nursing Care in hospital surgical inpatient settings, with scientific and reflective components, resulting from an action-research process on the focus of preoperative anxiety. The theoretical framework emerges from the available literature, and the practical framework emerges from the team's experience and opinion on the project. This phase of the report highlights the transfer to the practical context of the knowledge acquired in the academic context, thus contributing to the reasoned continuous improvement of the care provided. The development of nurses' learning and skills and nursing science itself should aim at meeting the health care needs of people and populations, and the progressive, continuous and differentiated training of professionals should seek care excellence, in creative ways that simultaneously satisfy the client and the institutions providing and regulating care. It is believed that the training mirrored in this report is congruent with this principle and that it will translate into the improvement of the care provided as a nurse, having also contributed to personal development.

Peripheral neuropathy in Parkinson's disease: prevalence and functional impact on gait and balance.

Peripheral neuropathy is a common problem in patients with Parkinson's disease. Peripheral neuropathy's prevalence in Parkinson's disease varies between 4.8-55%, compared with 9% in the general population. It remains unclear whether peripheral neuropathy leads to decreased motor performance in Parkinson's disease, resulting in impaired mobility and increased balance deficits. We aimed to determine the prevalence and type of peripheral neuropathy in Parkinson's disease patients and evaluate its functional impact on gait and balance. A cohort of consecutive Parkinson's disease patients assessed by movement disorders specialists based on the UK Brain Bank criteria underwent clinical, neurophysiological (nerve conduction studies and quantitative sensory testing) and neuropathological (intraepidermal nerve fibre density in skin biopsy punches) evaluation to characterize the peripheral neuropathy type and aetiology using a cross-sectional design. Gait and balance were characterized using wearable health-technology in OFF and ON medication states, and the main parameters were extracted using validated algorithms. A total of 99 Parkinson's disease participants with a mean age of 67.2 (±10) years and mean disease duration of 6.5 (±5) years were assessed. Based on a comprehensive clinical, neurophysiological and neuropathological evaluation, we found that 40.4% of Parkinson's disease patients presented peripheral neuropathy, with a predominance of small fibre neuropathy (70% of the group). In the OFF state, the presence of peripheral neuropathy was significantly associated with shorter stride length (P = 0.029), slower gait speed (P = 0.005) and smaller toe-off angles (P = 0.002) during straight walking; significantly slower speed (P = 0.019) and smaller toe-off angles (P = 0.007) were also observed during circular walking. In the ON state, the above effects remained, albeit moderately reduced. With regard to balance, significant differences between Parkinson's disease patients with and without peripheral neuropathy were observed in the OFF medication state during stance with closed eyes on a foam surface. In the ON states, these differences were no longer observable. We showed that peripheral neuropathy is common in Parkinson's disease and influences gait and balance parameters, as measured with mobile health-technology. Our study supports that peripheral neuropathy recognition and directed treatment should be pursued in order to improve gait in Parkinson's disease patients and minimize balance-related disability, targeting individualized medical care.

Neuropathology of central nervous system involvement in TTR amyloidosis.

Hereditary transthyretin amyloidosis (ATTRv) is a systemic disease caused by the accumulation of misfolded transthyretin (TTR). It usually presents with an adult-onset progressive axonal peripheral neuropathy and cardiomyopathy. In the central nervous system (CNS), variant TTR is produced by the choroid plexus and accumulates in the leptomeninges. CNS symptoms have been increasingly recognized in this population, including transient focal neurological episodes and stroke, particularly in patients with the V30M mutation and longstanding disease. The prevalence, pathophysiology, and progression of CNS involvement remain to be clarified. The present work explores if there is a recognizable sequence of CNS TTR deposition in ATTRv. We studied the topographical and severity distribution of TTR deposition in 16 patients with ATTRv, aged 27-69 years and with a mean disease duration of 10.9 years (range: 3-29). Our results suggest that CNS pathological involvement in V30M ATTRv occurs early in the disease course, probably starting in pre-symptomatic phases, and follows a distinct sequence. Leptomeninges and subarachnoid meningeal vessels are affected earlier, then followed by perforating cortical vessels and subpial deposition, and finally by deposition in the subependymal and basal ganglia vessels near the ependymal lining. Brainstem and spinal cord show early and severe involvement, with amyloid subpial deposition already seen in initial stages. Despite massive superficial amyloid deposition, no parenchymal deposition outside subpial or subependymal regions was found. Additionally, vascular lesions or superficial cortical siderosis were not frequent. Future studies with more patients from different populations and TTR mutations will be important to confirm these findings. Defining stages of TTR pathology in the CNS may be useful to better understand pathogenic mechanisms leading to symptoms and to interpret neuroimaging biomarkers.

Epithelial-Mesenchymal Plasticity Induced by Discontinuous Exposure to TGFß1 Promotes Tumour Growth.

Transitions between epithelial and mesenchymal cellular states (EMT/MET) contribute to cancer progression. We hypothesize that EMT followed by MET promotes cell population heterogeneity, favouring tumour growth. We developed an EMT model by on and off exposure of epithelial EpH4 cells (E-cells) to TGFß1 that mimics phenotypic EMT (M-cells) and MET. We aimed at understanding whether phenotypic MET is accompanied by molecular and functional reversion back to epithelia by using RNA sequencing, immunofluorescence (IF), proliferation, wound healing, focus formation and mamosphere formation assays as well as cell xenografts in nude mice. Phenotypic reverted epithelial cells (RE-cells) obtained after MET induction presented epithelial morphologies and proliferation rates resembling E cells. However, the RE transcriptomic profile and IF staining of epithelial and mesenchymal markers revealed a uniquely heterogeneous mixture of cell subpopulations with a high self-renewal ability. RE cell heterogeneity was stably maintained for long periods after TGFß1 removal both in vitro and in large tumours derived from the nude mice. Overall, we show that phenotypic reverted epithelial cells (RE cells) do not return to the molecular and functional epithelial state and present mesenchymal features related to aggressiveness and cellular heterogeneity that favour tumour growth in vivo. This work strengthens epithelial cell reprogramming and cellular heterogeneity fostered by inflammatory cues as a tumour growth-promoting factor in vivo.

Mortality by colon, lung, esophagus, prostate, cervix and breast cancers in Brazilian capitals, 2000-2015: a multilevel analysis.

This study aimed to analyze the role of period, geographic and socio demographic factors in cancer-related mortality by prostate, breast, cervix, colon, lung and esophagus cancer in Brazilians capitals (2000-2015). Ecological study using data of Brazilian Mortality Information. Multilevel Poisson models were used to estimate the adjusted risk of cancer mortality. Mortality rate levels were higher in males for colon, lung and esophageal cancers. Mortality rates were highest in the older. Our results showed an increased risk of colon cancer mortality in both sexes from 2000 to 2015, which was also evidenced for breast and lung cancers in women. In both genders, the highest mortality risk for lung and esophageal cancers was observed in Southern capitals. Midwestern, Southern and Southeastern capitals showed the highest mortality risk for colon cancer both for males and females. Colon cancer mortality rate increased for both genders, while breast and lung cancers mortality increased only for women. The North region showed the lowest mortality rate for breast, cervical, colon and esophageal cancers. The Midwest and Northeast regions showed the highest mortality rates for prostate cancer.

Mortality by colon, lung, esophagus, prostate, cervix and breast cancers in Brazilian capitals, 2000-2015: a multilevel analysis / Mortalidade por câncer de cólon, pulmão, esôfago, próstata, colo do útero e mama nas capitais brasileiras, 2000-2015: uma análise multinível

Abstract This study aimed to analyze the role of period, geographic and socio demographic factors in cancer-related mortality by prostate, breast, cervix, colon, lung and esophagus cancer in Brazilians capitals (2000-2015). Ecological study using data of Brazilian Mortality Information. Multilevel Poisson models were used to estimate the adjusted risk of cancer mortality. Mortality rate levels were higher in males for colon, lung and esophageal cancers. Mortality rates were highest in the older. Our results showed an increased risk of colon cancer mortality in both sexes from 2000 to 2015, which was also evidenced for breast and lung cancers in women. In both genders, the highest mortality risk for lung and esophageal cancers was observed in Southern capitals. Midwestern, Southern and Southeastern capitals showed the highest mortality risk for colon cancer both for males and females. Colon cancer mortality rate increased for both genders, while breast and lung cancers mortality increased only for women. The North region showed the lowest mortality rate for breast, cervical, colon and esophageal cancers. The Midwest and Northeast regions showed the highest mortality rates for prostate cancer.

Resumo Este estudo teve como objetivo analisar o papel de fatores temporais, geográficos e sociodemográficos na mortalidade por câncer de próstata, mama, colo do útero, cólon, pulmão e esôfago nas capitais brasileiras (2000-2015). Estudo ecológico utilizando informações brasileiras de mortalidade. Modelos de Poisson multinível foram usados ​​para estimar o risco ajustado de mortalidade por câncer. Os níveis de mortalidade foram maiores em homens para câncer de cólon, pulmão e esôfago. As taxas de mortalidade foram mais altas nos idosos. Nossos resultados mostraram risco aumentado de mortalidade por câncer de cólon em ambos os sexos de 2000 a 2015, o que também foi evidenciado para câncer de mama e de pulmão em mulheres. Em ambos os sexos, o maior risco de mortalidade para câncer de pulmão e esôfago foi observado nas capitais do Sul. As capitais do Centro-Oeste, Sul e Sudeste apresentaram o maior risco de mortalidade por câncer de cólon tanto para homens quanto para mulheres. A taxa de mortalidade por câncer de cólon aumentou para ambos os sexos, enquanto a mortalidade por câncer de mama e de pulmão aumentou apenas para as mulheres. A região Norte apresentou a menor taxa de mortalidade por câncer de mama, colo do útero, cólon e esôfago. As regiões Centro-Oeste e Nordeste apresentaram as maiores taxas de mortalidade por câncer de próstata.

Analysis of the Main Groups Victimized by Familiar Violence and by Violence by a Known Person in Brazil.

ABSTRACT: This study aims to evaluate the ratio of the number of cases of family violence and violence by a known person, over the four surveys that took place in 2006, 2007, 2009, and 2011, within the population treated in the Brazilian health services, according to demographic and socioeconomic characteristics. Data from the Vigilância de Violências e Acidentes survey was used. The variables age, victim sex, aggressor sex, race, and schooling level were considered in the analysis. This study pointed out decreasing trend in the number of violence-related care within the older age group. The number of familial violence-related care per victim sex was higher for male victims when the aggressor was female, and conversely, it was higher for female victims when the aggressor was male. The number of violence-related care was mostly higher in non-White people than in White. People with low schooling levels showed the highest ratio of the number of violence-related care.

Intermittent versus Continuous Catheterization and Differences in the Evolution of Labor: Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the differences between bladder emptying options (permanent catheterization and intermittent bladder emptying/spontaneous urination) regarding the effects on labor length, need of operative vaginal deliveries, and cesarean section rate. DATA SOURCES: The search was conducted in MEDLINE, Scopus, Web of Science, and The Cochrane Central Register of Controlled Trials databases. SELECTION OF STUDIES: The survey returned 964 studies. A total of 719 studies were evaluated by title and abstract, of which 4 were selected for inclusion. DATA COLLECTION: All references were inserted in the Rayyan QCRI tool (Rayyan Systems Inc., Cambridge, MA, USA). The full text of the selected articles was obtained so we could later decide whether or not to include them in this systematic review. DATA SYNTHESIS: No differences were found in the number of instrumented deliveries or in cesarean section rate between groups. CONCLUSIONS: After evaluating the studies performed on the topic, we concluded that there is no clear advantage to either method, although continuous catheterization was associated with a greater occurrence of eutocic births. In the remaining outcomes, there were no differences between catheterization types.

OBJETIVO: Avaliar as diferenças entre as opções de esvaziamento vesical (cateterismo permanente e esvaziamento vesical intermitente/micção espontânea) em relação aos efeitos na duração do trabalho de parto, necessidade de partos vaginais operatórios e taxa de cesárea. FONTES DE DADOS: A pesquisa foi realizada nas bases de dados MEDLINE, Scopus, Web of Science, e The Cochrane Central Register of Controlled Trials. SELEçãO DE ESTUDOS: A pesquisa retornou 964 estudos. Um total de 719 estudos foram avaliados por título e resumo, dos quais 4 foram selecionados para inclusão. COLETA DE DADOS: Todas as referências foram inseridas na ferramenta Rayyan QCRI (Rayyan Systems Inc., Cambridge, MA, EUA). O texto completo dos artigos selecionados foi obtido para posterior decisão de incluí-los nesta revisão sistemática. SíNTESE DOS DADOS: Não foram encontradas diferenças no número de partos instrumentados ou na taxa de cesariana entre os grupos. CONCLUSõES: Após avaliação dos estudos realizados sobre o tema, concluímos que não há vantagem clara de qualquer um dos métodos, embora o cateterismo contínuo tenha sido associado à maior ocorrência de partos eutócicos. Nos demais desfechos, não houve diferenças entre os tipos de cateterismo.

Intermittent versus Continuous Catheterization and Differences in the Evolution of Labor: Systematic Review and Meta-analysis / Cateterismo intermitente versus contínuo e diferenças na evolução do trabalho de parto: Revisão sistemática e meta-análise

Abstract Objective To evaluate the differences between bladder emptying options (permanent catheterization and intermittent bladder emptying/spontaneous urination) regarding the effects on labor length, need of operative vaginal deliveries, and cesarean section rate. Data Sources The search was conducted in MEDLINE, Scopus, Web of Science, and The Cochrane Central Register of Controlled Trials databases. Selection of Studies The survey returned 964 studies. A total of 719 studies were evaluated by title and abstract, of which 4 were selected for inclusion. Data Collection All references were inserted in the Rayyan QCRI tool (Rayyan Systems Inc., Cambridge, MA, USA). The full text of the selected articles was obtained so we could later decide whether or not to include them in this systematic review. Data Synthesis No differences were found in the number of instrumented deliveries or in cesarean section rate between groups. Conclusions After evaluating the studies performed on the topic, we concluded that there is no clear advantage to either method, although continuous catheterization was associated with a greater occurrence of eutocic births. In the remaining outcomes, there were no differences between catheterization types.

Resumo Objetivo Avaliar as diferenças entre as opções de esvaziamento vesical (cateterismo permanente e esvaziamento vesical intermitente/micção espontânea) em relação aos efeitos na duração do trabalho de parto, necessidade de partos vaginais operatórios e taxa de cesárea. Fontes de Dados A pesquisa foi realizada nas bases de dados MEDLINE, Scopus, Web of Science, e The Cochrane Central Register of Controlled Trials. Seleção de Estudos A pesquisa retornou 964 estudos. Um total de 719 estudos foram avaliados por título e resumo, dos quais 4 foram selecionados para inclusão. Coleta de Dados Todas as referências foram inseridas na ferramenta Rayyan QCRI (Rayyan Systems Inc., Cambridge, MA, EUA). O texto completo dos artigos selecionados foi obtido para posterior decisão de incluí-los nesta revisão sistemática. Síntese dos Dados Não foram encontradas diferenças no número de partos instrumentados ou na taxa de cesariana entre os grupos. Conclusões Após avaliação dos estudos realizados sobre o tema, concluímos que não hávantagem clara de qualquer um dos métodos, embora o cateterismo contínuo tenha sido associado à maior ocorrência de partos eutócicos. Nos demais desfechos, não houve diferenças entre os tipos de cateterismo.

Anti-Inflammatory Effects of Dietary Plant Stanol Supplementation Are Largely Dependent on the Intake of Cholesterol in a Mouse Model of Metabolic Inflammation.

The prevalence of metabolic disorders characterized by chronic inflammation has been on a sharp rise for decades. As such, tools that address metabolic and inflammatory dysregulation are of great importance. Plant stanols are well-known for reducing intestinal cholesterol absorption and may also have direct anti-inflammatory effects. In this study, our aim was to investigate to what extent the benefits of dietary plant stanol supplementation depend on dietary cholesterol intake in an experimental mouse model for cholesterol-induced metabolic inflammation. Here, we used Ldlr-/- mice transplanted with Npc1nih-derived bone marrow, featuring feature bone marrow-derived immune cells characterized by chronic inflammation induced by lysosomal lipid accumulation. Npc1nih- and Npc1wt-transplanted mice were placed on either a high fat, high cholesterol (HFC) or on a chow diet low in cholesterol, with or without 2% plant stanols supplementation. At the end of the study, the metabolic and inflammatory status of the mice was analyzed. Plant stanol supplementation to the HFC diet reduced liver cholesterol levels and improved lipid metabolism and liver inflammation, particularly in Npc1nih-tp mice. In contrast, plant stanol supplementation to the chow diet did not significantly improve the aforementioned parameters, though similar reductive trends to those in the HFC diet setting were observed regarding liver cholesterol accumulation and liver inflammatory markers. The effects of dietary plant stanol supplementation on dietary cholesterol-induced inflammation are largely dependent on dietary cholesterol intake. Future research should verify whether other models of metabolic inflammation exhibit similar stanol-related effects on inflammation.

Advantages of an Automated Method Compared With Manual Methods for the Quantification of Intraepidermal Nerve Fiber in Skin Biopsy.

Intraepidermal nerve fiber density (IENFD) measurements in skin biopsy are performed manually by 1-3 operators. To improve diagnostic accuracy and applicability in clinical practice, we developed an automated method for fast IENFD determination with low operator-dependency. Sixty skin biopsy specimens were stained with the axonal marker PGP9.5 and imaged using a widefield fluorescence microscope. IENFD was first determined manually by 3 independent observers. Subsequently, images were processed in their Z-max projection and the intradermal line was delineated automatically. IENFD was calculated automatically (fluorescent images automated counting [FIAC]) and compared with manual counting on the same fluorescence images (fluorescent images manual counting [FIMC]), and with classical manual counting (CMC) data. A FIMC showed lower variability among observers compared with CMC (interclass correlation [ICC] = 0.996 vs 0.950). FIMC and FIAC showed high reliability (ICC = 0.999). A moderate-to-high (ICC = 0.705) was observed between CMC and FIAC counting. The algorithm process took on average 15 seconds to perform FIAC counting, compared with 10 minutes for FIMC counting. This automated method rapidly and reliably detects small nerve fibers in skin biopsies with clear advantages over the classical manual technique.

Myosteatosis in NAFLD patients correlates with plasma Cathepsin D.

Previously, we have shown that hepatic lipid accumulation induces the secretion of cathepsin D (CTSD), and that plasma CTSD levels are associated with increased inflammation and disease severity in nonalcoholic fatty liver disease (NAFLD). Although it is clear that the liver is a major source of plasma CTSD, it is unknown whether other metabolically active organs such as the muscle, also associate with plasma CTSD levels in NAFLD patients. Therefore, the aim of this study was to explore the relation between lipid accumulation in the muscle (myosteatosis) and plasma CTSD levels in forty-five NAFLD patients. We observed that hepatic steatosis positively associated with plasma CTSD levels, confirming the previously established link between plasma CTSD and the liver. Furthermore, a positive association between myosteatosis and plasma CTSD levels was observed, which was independent of sex, age, BMI, waist circumference and hepatic steatosis. By establishing a positive association between myosteatosis and plasma CTSD levels, our findings suggest that, in addition to the liver, the muscle is also linked to plasma CTSD levels in NAFLD patients. The observed link between myosteatosis and plasma CTSD levels supports the concept of a significant role of the skeletal muscle in metabolic disturbances in metabolic syndrome-related disorders.

The Effect of Continuous Low-Intensity Exposure to Electromagnetic Fields from Radio Base Stations to Cancer Mortality in Brazil.

BACKGROUND: this study aims to estimate the rate of death by cancer as a result of Radio Base Station (RBS) radiofrequency exposure, especially for breast, cervix, lung, and esophagus cancers. METHODS: we collected information on the number of deaths by cancer, gender, age group, gross domestic product per capita, death year, and the amount of exposure over a lifetime. We investigated all cancer types and some specific types (breast, cervix, lung, and esophagus cancers). RESULTS: in capitals where RBS radiofrequency exposure was higher than 2000/antennas-year, the average mortality rate was 112/100,000 for all cancers. The adjusted analysis showed that, the higher the exposure to RBS radiofrequency, the higher cancer mortality was. The highest adjusted risk was observed for cervix cancer (rate ratio = 2.18). The spatial analysis showed that the highest RBS radiofrequency exposure was observed in a city in southern Brazil that also showed the highest mortality rate for all types of cancer and specifically for lung and breast cancer. CONCLUSION: the balance of our results indicates that exposure to radiofrequency electromagnetic fields from RBS increases the rate of death for all types of cancer.

The Influence of a Conjugated Pneumococcal Vaccination on Plasma Antibody Levels against Oxidized Low-Density Lipoprotein in Metabolic Disease Patients: A Single-Arm Pilot Clinical Trial.

As a mediator between lipid metabolism dysfunction, oxidative stress and inflammation, oxidized low-density lipoprotein (oxLDL) is a promising therapeutical target in a wide range of metabolic diseases. In mice, pneumococcal immunization increases anti-phosphorylcholine and oxLDL antibody levels, and reduces atherosclerosis, non-alcoholic steatohepatitis and Niemann-Pick disease burden. These findings suggest that pneumococcal vaccination may be a useful preventive and therapeutical strategy in metabolic disease patients. In this pilot clinical trial, our aim was to determine whether the administration of a pneumococcal vaccine increases anti-phosphorylcholine and anti-oxLDL antibody levels in metabolic disease patients. The following patients were enrolled: four patients with familial partial lipodystrophy (all women, mean age 32 years old); three familial hypercholesterolemia patients (one girl, two boys; mean age 13 years); and two Niemann-Pick type B (NP-B) patients (two men, mean age 37.5 years old). Participants received one active dose of a 13-valent conjugated pneumococcal vaccine (Prevenar 13) and were followed-up for four weeks. Four weeks after Prevenar 13 vaccination, no differences were observed in patients' levels of anti-oxLDL IgM or IgG antibodies. In addition, we observed a reduction in anti-phosphorylcholine (anti-PC) IgM antibody levels, whereas no differences were observed in anti-PC IgG antibody titers. These findings indicate that Prevenar 13 vaccination does not induce an immune response against oxLDL in patients with metabolic diseases. Therefore, Prevenar 13 is not suited to target the metabolic disruptor and pro-inflammatory mediator oxLDL in patients.