Discovery of novel fluorescent azaindoles with cytotoxic action in A2780 ovarian carcinoma cells.

Azaindole scaffold is a privileged structure in medicinal chemistry and some derivatives have demonstrated to be potential anticancer drugs. Herein, a set of novel azaindoles, comprising the four regioisomers, bearing a morpholine (azaindoles 3a-d) and N-methyl-N-benzylamine (azaindoles 4a-d) groups were prepared. Among these compounds, azaindoles 4 exhibited higher cytotoxicity against the ovarian cancer cell line A2780 and normal dermal fibroblasts compared to azaindoles 3. Furthermore, azaindoles 4b and 4c promoted a delay in the cell cycle of the cancer cell line, inspiring an investigation into the intracellular localization of these derivatives.

The Pleural Mesothelioma Cases and Mortality in Portugal in 2014-2020: A Descriptive Study.

BACKGROUND: The incidence and mortality of pleural mesothelioma (PM) reflect the production and consumption of asbestos over time. However, despite the current global concern, these data remain to be known. OBJECTIVE: Our aim was to carry out a descriptive analysis of PM cases and mortality from some Portuguese databases between 2014 and 2020. METHODS: A retrospective observational study was carried out between 2014 and 2020. Data on the number of PM cases were provided by the Portuguese Cancer Registry, and data on mortality were from the Portuguese Death Certificate Information System. RESULTS: Between 2014 and 2020, 315 cases of PM were reported, with 222 (70.5%) men. The average age of patients was 72.1, with the highest number of cases in patients aged >70 years (n = 198; 62.9%). The highest number of cases was reported in 2018 (n = 62; 19.7%). Regarding mortality, 169 deaths were reported, with 126 (74.6%) men and mostly in individuals aged >70 years (n = 109; 64.5%). It is estimated that around 520 years of potential life were lost. The highest number of deaths occurred in 2015 (n = 33; 19.5%). CONCLUSION: It is mandatory to reinforce the need for surveillance programs that allow us to gather real and reliable data and eliminate asbestos-related diseases.

Classical and Nonclassical Nucleation Mechanisms of Insulin Crystals.

Although the Classical Nucleation Theory (CNT) is the most consensual theory to explain protein nucleation mechanisms, experimental observations during the shear-induced assays suggest that the CNT does not always describe the insulin nucleation process. This is the case at intermediate precipitant (ZnCl2) solution concentrations (2.3 mM) and high-temperature values (20 and 40 °C) as well as at low precipitant solution concentrations (1.6 mM) and low-temperature values (5 °C). In this work, crystallization events following the CNT registered at high precipitant solution concentrations (3.1 and 4.7 mM) are typically described by a Newtonian response. On the other hand, crystallization events following a nonclassical nucleation pathway seem to involve the formation of a metastable intermediate state before crystal formation and are described by a transition from Newtonian to shear-thinning responses. A dominant shear-thinning behavior (shear viscosity values ranging more than 6 orders of magnitude) is found during aggregation/agglomeration events. The rheological analysis is complemented with different characterization techniques (Dynamic Light Scattering, Energy-Dispersive Spectroscopy, Circular Dichroism, and Differential Scanning Calorimetry) to understand the insulin behavior in solution, especially during the occurrence of aggregation/agglomeration events. To the best of our knowledge, the current work is the first study describing nonclassical nucleation mechanisms during shear-induced crystallization experiments, which reveals the potential of the interdisciplinary approach herein described and opens a window for a clear understanding of protein nucleation mechanisms.

Relationship between event-related potentials and cognitive dysfunction in multiple sclerosis: A systematic review.

OBJECTIVE: This systematic review aimed to evaluate if event-related potentials (ERPs) can be a relevant tool for cognitive dysfunction diagnosis in Multiple Sclerosis (MS). METHODS: Four databases were consulted (PubMed, Embase, Scielo, and Web of Science). The included studies should include adults with clear MS diagnoses, independently of having cognitive complaints, and all should have been submitted to ERPs (P300, N400 or mismatch negativity (MMN)). The main outcomes evaluated were ERPs' amplitude and/or latency. RESULTS: 425 studies were obtained initially from all databases, with 26 studies fulfilling the eligibility criteria. P300 was the most used ERP (25 studies), showing a reduced amplitude or an increased latency in 84% of those. N400 was evaluated in one study, showing also abnormal results. MMN was addressed in two studies with inconsistent findings. Some studies further suggest that ERPs may show earlier abnormal results compared with neuropsychological tests. CONCLUSIONS: Most MS patient groups revealed ERP abnormalities, suggesting that these neurophysiological tests may be a relevant and appropriate diagnostic aid method for cognitive impairment in MS. SIGNIFICANCE: The use of ERPs in MS patients seems able to demonstrate cognitive impairment and its use should be considered as part of the regular patient evaluation.

Effects of high dietary inclusion of Arthrospira platensis, either extruded or supplemented with a super-dosing multi-enzyme mixture, on broiler growth performance and major meat quality parameters.

BACKGROUND: This investigation assessed the effects of high dietary inclusion of Spirulina (Arthrospira platensis) on broiler chicken growth performance, meat quality and nutritional attributes. For this, 120 male broiler chicks were housed in 40 battery brooders (three birds per brooder). Initially, for 14 days, a standard corn and soybean meal diet was administered. Subsequently, from days 14 to 35, chicks were assigned to one of the four dietary treatments (n = 10 per treatment): (1) control diet (CTR); (2) diet with 15% Spirulina (SP); (3) diet with 15% extruded Spirulina (SPE); and (4) diet with 15% Spirulina plus a super-dosing enzymes supplement (0.20% pancreatin extract and 0.01% lysozyme) (SPM). RESULTS: Throughout the experimental period, both SP and SPM diets resulted in decreased final body weight and body weight gain compared to control (p < 0.001), with the SPE diet showing comparable results to CTR. The SPE diet prompted an increase in average daily feed intake (p = 0.026). However, all microalga treatments increased the feed conversion ratio compared to CTR. Dietary inclusion of Spirulina notably increased intestinal content viscosity (p < 0.010), which was mitigated by the SPM diet. Spirulina supplementation led to lower pH levels in breast meat 24 h post-mortem and heightened the b* colour value in both breast and thigh meats (p < 0.010). Furthermore, Spirulina contributed to an increased accumulation of total carotenoids, n-3 polyunsaturated fatty acids (PUFA), and saturated fatty acids (SFA), while diminishing n-6 PUFA, thus altering the n-6/n-3 and PUFA/SFA ratios favourably (p < 0.001). However, it also reduced zinc concentration in breast meat (p < 0.001). CONCLUSIONS: The findings indicate that high Spirulina levels in broiler diets impair growth due to increased intestinal viscosity, and that extrusion pre-treatment mitigates this effect. Despite reducing digesta viscosity, a super-dosing enzyme mix did not improve growth. Data also indicates that Spirulina enriches meat with antioxidants and n-3 PUFA but reduces α-tocopherol and increases saturated fats. Reduced zinc content in meat suggests the need for Spirulina biofortification to maintain its nutritional value.

Higher levels of cytokines in patients with critical limb threatening ischemia.

OBJECTIVE: Inflammation is a key element in the initiation and progression of peripheral arterial disease (PAD). Understanding the impact of inflammatory molecules, as cytokines in PAD could help us to improve the prognosis of these patients. The main goal of this study was to compare the serum level of cytokines between patients with claudication to those with critical limb treating ischemia (CLTI). The second objective was to evaluate the relationship between the levels of cytokines and death or amputation rate. METHODS: An observational, single-centre and prospective study was conducted from January 2018 to July 2022. The study was approved by the ethical commission of the Local Hospital (75/2017). Patients with PAD, suggested by the clinical history and objective examination and, confirmed with ankle-brachial index (ABI) attending Vascular Surgery consultations of the first author were included. The following exclusion criteria were applied: i) bedridden individuals or subjects who refused to participate in the protocol; ii) diseases responsible for body composition changes or pro-inflammatory state; iii) recent diet change, iv) active malignancy, v) auto-immune disease, vi) active infection, vii) chronic renal failure (GFR <30 mL/min/1.73m2) or viii) heart failure in the past three months. This cohort was observed at admission, three, six and twelve months. A panel of 27 cytokines was determined with ELISA, at baseline. RESULTS: We included 119 subjects (mean age: 67.58 ± 9.60 years-old; 79.80% males), 65 patients with claudication and 54 with CLTI. From the 27 cytokines analysed, patients with CLTI, when compared to those with claudication, had a higher serum level of 11 cytokines: IL1ra; IL-6; IL-8; IL12 p70; G-CSF; IP-10; MCP-1; MIP-1α; PDGF-ß, RANTES, TNF-α. From the group of patients with CLTI those who underwent a major amputation had a higher serum level of FGF-basic [Median = 49.04; IQR = 37.03-52.49; versus Median = 33.04; IQR =28.60-38.98; p = 0.001]. CONCLUSIONS: Patients with CLTI have higher serum level of inflammatory cytokines, which may have role in the prognosis of these patients.

Protocol: The effect of restorative justice interventions for young people on offending and reoffending: A systematic review.

This is the protocol for a Campbell systematic review. The objectives are as follows. The primary aim of this mixed methods review is to synthesise the available evidence regarding the effectiveness of restorative justice interventions (RJIs) for reducing offending and reoffending outcomes in children and young people. We are also particularly interested in the impact of RJIs on children and young peoples' violent offending and violent reoffending. A second aim of the review is to examine whether the magnitude of effectiveness of RJIs may be influenced by study characteristics such as the population (e.g., age, ethnicity, or sex), the form of intervention (e.g., face-to-face mediation compared to family group conferencing), the place of delivery of the intervention (e.g., in independent office, in court), implementation (e.g., trained facilitators, dose, fidelity) and methodology (e.g., randomised controlled trial). The third aim of the review is to synthesise the qualitative evidence about RJ to develop a better contextual understanding of how these programmes may work and to elucidate factors that might increase the efficacy and implementation of RJ interventions. The specific research questions this systematic review aims to address are: (1) Do RJ interventions reduce children and young people's involvement in offending or reoffending relative to a comparison group? [RQ1]. (2) Is there variation in the impact of different RJ approaches on young people's involvement in offending or reoffending? [RQ2]. (3) Is there variation in the impact of RJIs on children and young people's offending or reoffending depending on the characteristics of the participants taking part in the RJI (e.g., sex, age, ethnicity)? [RQ3]. (4) What characteristics of RJIs, influence the effectiveness of RJIs for children and young people's offending and reoffending? [RQ4]. (5) What are the most notable barriers and facilitators, as reported by participants (e.g., the victims, children/young people, or mediators who have taken part in an evaluation of an RJI, or those children or young people who were meant to take part in an evaluation but ultimately did not), to the implementation of RJIs to reduce later offending or reoffending? [RQ5].

A unifying mechanism for seipin-mediated lipid droplet formation.

Lipid droplets (LDs) are dynamic organelles essential for cellular lipid homeostasis. Assembly of LDs occurs in the endoplasmic reticulum (ER), and the conserved ER membrane protein seipin emerged as a key player in this process. Here, we review recent advances provided by structural, biochemical, and in silico analysis that revealed mechanistic insights into the molecular role of the seipin complexes and led to an updated model for LD biogenesis. We further discuss how other ER components cooperate with seipin during LD biogenesis. Understanding the molecular mechanisms underlying seipin-mediated LD assembly is important to uncover the fundamental aspects of lipid homeostasis and organelle biogenesis and to provide hints on the pathogenesis of lipid storage disorders.

[Correction to the Article "Ophthalmology Census 2021: A Demographic Characterisation of Ophthalmologists in Portugal", Published on Acta Med Port (In Press), https://doi.org/10.20344/amp.20321]. / Errata ao Artigo "Estudo Demográfico da População de Oftalmologistas em Portugal: Censo de Oftalmologia 2021", Publicado em Acta Med Port (In Press), https://doi.org/10.20344/amp.20321.

On page 5, 3rd paragraph, line 7, where it reads, (in red): "(...) considering the international recommendation (1:10 000)8" It should read (in blue): "(...) considering the international recommendation (0.5:10 000)8" Still on page 5, 5th paragraph, line 8, where it reads, (in red): "(...) in the 40 - 50-year age group" It should read (in blue): "(...) below the 40 - 50-year age group" On page 8, key of Table 1, line 5, where it reads, (in red): "1: PORTATA 2021;" It should read (in blue): "1: PORDATA 2021;" Article published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20321.

Na página 5, 3º parágrafo, linha 7, onde se lê, (a vermelho): "(...) considering the international recommendation (1:10 000)8" Deverá ler-se (a azul): "(...) considering the international recommendation (0.5:10 000)8" Ainda na página 5, 5º parágrafo, linha 8, onde se lê, (a vermelho): "(...) in the 40 - 50-year age group" Deverá ler-se (a azul): "(...) below the 40 - 50-year age group" Na página 8, legenda da Tabela 1, linha 5, onde se lê, (a vermelho): "1: PORTATA 2021;" Deverá ler-se (a azul): "1: PORDATA 2021;" Artigo publicado com erros: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20321.

Impact of high Spirulina diet, extruded or supplemented with enzymes, on blood cells, systemic metabolites, and hepatic lipid and mineral profiles of broiler chickens.

The impact of 15% dietary inclusion of Spirulina (Arthrospira platensis) in broiler chickens was explored, focusing on blood cellular components, systemic metabolites and hepatic lipid and mineral composition. From days 14 to 35 of age, 120 broiler chickens were divided and allocated into four dietary treatments: a standard corn and soybean meal-based diet (control), a 15% Spirulina diet, a 15% extruded Spirulina diet, and a 15% Spirulina diet super-dosed with an enzyme blend (0.20% porcine pancreatin plus 0.01% lysozyme). The haematological analysis revealed no significant deviations (p > 0.05) in blood cell counts across treatments, suggesting that high Spirulina inclusion maintains haematological balance. The systemic metabolic assessment indicated an enhanced antioxidant capacity in birds on Spirulina diets (p < 0.001), pointing toward a potential reduction in oxidative stress. However, the study noted a detrimental impact on growth performance metrics, such as final body weight and feed conversion ratio (both p < 0.001), in the Spirulina-fed treatments, with the super-dosed enzyme blend supplementation failing to alleviate these effects but with extrusion mitigating them. Regarding hepatic composition, birds on extruded Spirulina and enzyme-supplemented diets showed a notable increase in n-3 fatty acids (EPA, DPA, DHA) (p < 0.001), leading to an improved n-6/n-3 PUFA ratio (p < 0.001). Despite this positive shift, a reduction in total hepatic lipids (p = 0.003) was observed without a significant change in cholesterol levels. Our findings underscore the need for further exploration into the optimal inclusion levels, processing methods and potential enzymatic enhancements of Spirulina in broiler diets. Ultimately, this research aims to strike a balance between promoting health benefits and maintaining optimal growth performance in poultry nutrition.

Reversion of the Inflammatory Markers in Patients With Chronic Limb-Threatening Ischemia.

BACKGROUND: Peripheral artery disease is characterized by an intense inflammatory process that can be associated with a higher mortality rate, particularly in chronic limb-threatening ischemia (CLTI). This study aims to compare the evolution of inflammatory markers between patients with claudication with those with CLTI at 3, 6, and 12 months. METHODS AND RESULTS: An observational, single-center, and prospective study was conducted. A total of 119 patients with peripheral artery disease (65 with claudication and 54 with CLTI) were observed and inflammatory markers collected at admission and 3, 6, and 12 months. At admission, patients with CLTI, when compared with patients with claudication, had significantly higher serum levels of C-reactive protein and fibrinogen (positive acute-phase proteins) and lower serum level of albumin, total cholesterol, and high-density lipoprotein (negative acute-phase proteins): C-reactive protein (g/dL), 2.90 (25th-75th percentile, 2.90-4.90) versus 6.80 (25th-75th percentile, 2.90-53.26) (P=0.000); fibrinogen (mg/dL), 293.00 (25th-75th percentile, 269.25-349.00) versus 415.50 (25th-75th percentile, 312.00-615.75) (P=0.000); total cholesterol (mg/dL), 161.79±95% [152.74-170.85] versus 146.42%±95% [135.30-157.53] (P=0.034); high-density lipoprotein (mg/dL), 50.00 (25th-75th percentile, 41.00-60.00) versus 37.00 (25th-75th percentile, 30.00-45.50) (P=0.000); albumin (g/dL): 4.00 (25th-75th percentile, 3.70-4.20) versus 3.60 (25th-75th percentile, 3.10-4.00) (P=0.003). The association between CLTI and total cholesterol was lost after adjusting for confounders. Three months after the resolution of the CLTI, there was an increase in the levels of negative acute-phase proteins and a decrease in positive acute-phase proteins. These inflammatory proteins did not register an evolution in patients with claudication. The differences in the inflammatory proteins between groups disappeared at 6 months. CONCLUSIONS: CLTI has an inflammatory environment that can be partially reverted after resolution of the ischemic process, emphasizing the importance of timely intervention.

Inflammatory Cells in Adipose Tissue and Skeletal Muscle of Patients with Peripheral Arterial Disease or Chronic Venous Disease: A Prospective, Observational, and Histological Study.

The main goal of this study was to assess whether the presence of peripheral arterial disease (PAD) correlates with increased inflammatory cell infiltration. An observational, single-centre, and prospective study was conducted from January 2018 to July 2022. Clinical characteristics and anthropometric measures were registered. Consecutive PAD patients with surgical indications for a common femoral artery approach and patients with varicose veins with an indication for surgical ligation of the saphenofemoral junction were included. In both groups, samples of sartorius skeletal muscle, subcutaneous adipose tissue (SAT), and perivascular adipose tissue (PVAT) were collected from the femoral region. We analysed the characteristics of adipocytes and the presence of haemorrhage and inflammatory cells in the samples of PVAT and SAT via haematoxylin-eosin staining. We found that patients with PAD had significantly more inflammatory cells in PVAT [16 (43.24%) vs. 0 (0%) p = 0.008]. Analysing SAT histology, we observed that patients with PAD had significantly more CD45+ leucocytes upon immunohistochemical staining [32 (72.73%) vs. 3 (27.27%) p = 0.005]. Upon analysing skeletal muscle histology with haematoxylin-eosin staining, we evaluated skeletal fibre preservation, as well as the presence of trauma, haemorrhage, and inflammatory cells. We registered a significantly higher number of inflammatory cells in patients with PAD [well-preserved skeletal fibres: PAD = 26 (63.41%) vs. varicose veins = 3 (37.50%) p = 0.173; trauma: PAD = 4 (9.76%) vs. varicose veins = 2 (25.00%) p = 0.229; haemorrhage: PAD = 6 (14.63%) vs. varicose veins = 0 (0%) p = 0.248; inflammatory cells: PAD = 18 (43.90%) vs. varicose veins = 0 (0%) p = 0.018]. Patients with PAD had a higher number of inflammatory cells in skeletal muscle and adipose tissue (PVAT and SAT) when compared with those with varicose veins, emphasizing the role of inflammation in this group of patients.

Ophthalmology Census 2021: A Demographic Characterisation of Ophthalmologists in Portugal.

INTRODUCTION: Human resources in ophthalmology have recently received particular attention, and it has been questioned whether there is a sufficient number of workers. The aim of this study was to analyze and characterize Portugal's ophthalmologist population. METHODS: In this descriptive, cross-sectional study, an online questionnaire was sent to all ophthalmologists registered with the Portuguese College of Ophthalmology in December 2021. Information on the following variables was collected and analyzed: demographic factors, professional qualifications, professional activity, weekly professional activity and medium-term plans. RESULTS: Among the 910 registered ophthalmologists, a response rate of 64.7% was achieved. There were 0.9 ophthalmologists for every 10 000 inhabitants, 0.45:10 000 working in the public sector (0.35:10 000 full-time equivalent). Among the respondents, 57.6% were over 50 years old (59.6% male), 97.3% were Portuguese, 46.7% completed their residency in the Lisbon region, 27.3% complemented their programme with additional training, 9.5% had a PhD and approximately 58% lived and worked in large urban centres. Regarding professional activity, 58.5% of the respondents worked in the public sector (4.2% exclusively), while 67.9% worked in different economic sectors. The median number of weekly working hours reported was 45 hours, with those in the public sector reporting 35 hours. Private/social sector work and public sector work accounted for 12 926 hours/week and 10 808 hours/week, respectively. It was found that 31.4% of the respondents provided emergency medical services and that 52.8% performed surgical procedures more than once a week. Looking ahead, 38.7% of the ophthalmologists intended to reduce their workload within the next five years due to family reasons, fatigue and demotivation. The projected rate of retirement or cessation of activity in the next five years was estimated to be 1.7%, while an average of 20 new ophthalmologists are expected to enter the profession annually, resulting in a generational balance of 0.8%. CONCLUSION: While the number of ophthalmologists in Portugal meets the international recommendations, there is a shortage in the public sector and most ophthalmologists work in large urban centres. The number of ophthalmologists in Portugal is expected to be stable for the next five years.

Effects of HCV Clearance with Direct-Acting Antivirals (DAAs) on Liver Stiffness, Liver Fibrosis Stage and Metabolic/Cellular Parameters.

INTRODUCTION: Chronic hepatitis C (CHC) is a clinical and pathological syndrome with various causes and is characterized by varying degrees of hepatocellular necrosis and inflammation. It is a significant cause of liver transplantation and liver-related death worldwide. The hepatic manifestations of CHC are typically characterized by slowly progressing liver fibrosis, which is a non-specific and often disproportionate response to tissue damage. A large majority of HCV patients have extrahepatic manifestations with varying degrees of severity. HCV infection is a risk factor for cardiovascular disease and diabetes mellitus, which increases insulin resistance, oxidative stress, and iron overload and causes chronic systemic inflammation. HCV infection is treated using direct-acting antivirals (DAAs) with cure rates of over 95 percent, minimal side effects, and shorter therapeutic courses. Despite the effective elimination of the virus, it seemed pertinent to understand to what extent HCV clearance eliminates or attenuates all the systemic alterations already induced by the virus during infection and chronicity. OBJECTIVES: Our study aimed to determine whether eliminating HCV with DAAs alters the severity of liver disease (liver stiffness and liver fibrosis stage by TE) and the metabolic/cellular profile of patients with CHC. MATERIALS AND METHODS: A group of 329 CHC patients from a Gastroenterology and Hepatology outpatient department were prospectively studied. Of these, 134 were also studied with DAAs. The liver fibrosis stage was evaluated by transient elastography (TE) using a FibroScan® device, and two groups were established for the analysis of liver stiffness (LS): mild and moderate stiffness (fibrosis F1 and F2; F1/2) and severe stiffness (fibrosis and cirrhosis F3 and F4; F3/4). Metabolic/cellular parameters were evaluated before and after antiviral treatment using standard methods: alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl-transpeptidase (γ-GT), haptoglobin (Hp), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), free iron (Fe), transferrin saturation (TS), total iron binding capacity (TIBC), ferritin (Ft), glycemia, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and platelets count. The results were statistically analyzed using SPSS 24.0 for Windows. RESULTS: Comparing the fibrosis stage before and after DAAs treatment, we verify a reduction in LS in 85.7% of patients and an improvement in liver fibrosis stage in 22.2% of them after DAAs treatment. Before DAAs treatment, patients showed a 2.410 risk for higher fibrosis stages (F3/4). Comparing metabolic/cellular parameters before and after DAAs treatment, patients showed lower ALP, AST, ALT, γGT, TG, Fe, TIBC, and Ft values and higher TC, LDL, and Hp values after treatment. As such, HCV elimination reduces iron overload and insulin resistance. On the other hand, it caused dyslipidemia, raising total cholesterol and LDL to levels outside the reference values. The improvement in the liver fibrosis stage by TE was mainly associated with higher baseline platelet count and HDL values and lower insulin resistance. CONCLUSIONS: With this study, we were able to contribute to the knowledge of the effects of HCV elimination with DAAs on liver disease and metabolic profile to improve the quality of treatment and follow-up of these patients after HCV elimination.

Efficacy of Cold Atmospheric Plasma vs. Chemotherapy in Triple-Negative Breast Cancer: A Systematic Review.

Breast cancer is a growing disease, with a high worldwide incidence and mortality rate among women. Among the various types, the treatment of triple-negative breast cancer (TNBC) remains a challenge. Considering the recent advances in cold atmospheric plasma (CAP) cancer research, our goal was to evaluate efficacy data from studies based on chemotherapy and CAP in TNBC cell lines and animal models. A search of the literature was carried out in the PubMed, Web of Science, Cochrane Library, and Embase databases. Of the 10,999 studies, there were fifty-four in vitro studies, three in vivo studies, and two in vitro and in vivo studies included. MDA-MB-231 cells were the most used. MTT, MTS, SRB, annexin-V/propidium iodide, trypan blue, and clonogenic assay were performed to assess efficacy in vitro, increasing the reliability and comprehensiveness of the data. There was found to be a decrease in cell proliferation after both chemotherapy and CAP; however, different protocol settings, including an extensive range of drug doses and CAP exposure times, were reported. For both therapies, a considerable reduction in tumor volume was observed in vivo compared with that of the untreated group. The treatment of TNBC cell lines with CAP proved successful, with apoptosis emerging as the predominant type of cellular death. This systematic review presents a comprehensive overview of the treatment landscape in chemotherapy and CAP regarding their efficacy in TNBC cell lines.

Effects of Particle Size on Physicochemical and Nutritional Properties and Antioxidant Activity of Apple and Carrot Pomaces.

The food processing industry is growing rapidly and producing large amounts of by-products, such as pomaces, which are considered as no-value waste and cause significant environmental pollution. The main by-products of fruit juice processing companies are apple and carrot pomaces, which can be used to create new functional food products. In the present study, the effects of particle size (PS) on the proximate composition, nutritional properties, and antioxidant activity of apple pomace flour (APF) and carrot pomace flour (CPF) were determined. Four different PS fractions, PS > 1 mm, 1 > PS > 0.71 mm, 0.71 > PS > 0.18 mm, and 0.18 > PS > 0.075 mm were used for the present study. Their vitamin, carotenoid, organic acid, and reducing sugar contents were determined using HPLC. The proximate compositions of each PS fraction of the AP and CP flours were determined using recommended international standard methods. DPPH, FRAP, and Folin-Ciocalteu methods were used to measure their antioxidant activity and total phenolic compounds, respectively. The moisture content (around 12.1 mg/100 g) was similar in all PS fractions and in both flours. The APF had lower protein (4.3-4.6 g/100 g dw) and ash (1.7-2.0 g/100 g dw) contents compared to the CPF, with protein contents ranging from 6.4-6.8 g/100 g dw and ash contents ranging from 5.8-6.1 g/100 g dw. Smaller particles, regardless of flour type, exhibited higher sugar and phenolic contents and antioxidant activity, while vitamins were more abundant in particles larger than 1 mm. In the APF, larger particles had a higher fiber content than smaller particles, while their fat content was the lowest. PS also had an impact on the results of the carotenoid contents. This study underscores the direct impact of PS on the distribution of sugars, crude fiber, fat, carotenoids, vitamins, total phenolic compounds, and antioxidant activity in pomaces.

Multidisciplinary Team Care in Pituitary Tumours.

The optimal care for patients with pituitary tumours is best provided in a multidisciplinary and collaborative environment, which requires the contribution of multiple medical specialties working together. The benefits and advantages of the pituitary multidisciplinary team (MDT) are broad, and all relevant international consensus and guidelines in the field recommend that patients with pituitary tumours should always be managed in a MDT. Endocrinologists and neurosurgeons are normally the leading specialties within the pituitary MDT, supported by many other specialties with significant contributions to the diagnosis and management of pituitary tumours, including neuropathology, neuroradiology, neuro-ophthalmology, and otorhinolaryngology, among others. Here, we review the literature concerning the concepts of Pituitary MDT/Pituitary Tumour Centre of Excellence (PTCOE) in terms of their mission, goals, benefits, structure, proposed models of function, and barriers, and we also provide the views of different specialists involved in our Pituitary MDT.

Peri-Carotid Adipose Tissue and Atherosclerosis at Carotid Bifurcation.

Vulnerable carotid plaques are responsible for 20% of the ischemic strokes. The identification of these asymptomatic carotid plaques that will become symptomatic is essential but remains unclear. Our main goal was to investigate whether the amount of the peri-carotid adipose tissue, estimated by the extra-media thickness (EMT), is associated with the atherosclerotic characteristics at the carotid bifurcation in patients with PAD. An observational, prospective, single-center, longitudinal study was conducted. Overall, 177 patients were subjected to carotid Doppler ultrasound at the study admission. The following data were collected: EMT, intima-media thickness (IMT), the presence of carotid plaques, the area of the highest plaque, the presence of "acute culprit" carotid stenosis, and the grade of internal carotid stenosis. "Acute culprit" carotid stenosis was defined as a significant atherosclerotic plaque that leads to a neurologic event within 15 days. From each carotid bifurcation, a right and a left EMT were determined. We analyzed both the mean EMTs (calculated as the mean between the right and the left EMT) and the EMT ipsilateral to the carotid bifurcation. The presence of carotid plaques was associated with a higher mean EMT [Median = 1.14; IQR = 0.66 versus Median = 0.97; IQR = 0.40; p = 0.001]. A positive correlation was found between the mean EMT and IMT (right: ρ = 0.20; p = 0.010; left: ρ = 0.21; p = 0.007) and between the mean EMT and the area of the largest carotid plaque (right: ρ = 0.17; p = 0.036; left: ρ = 0.22; p = 0.004). Left carotid stenosis ≥ 70% was associated with higher ipsilateral EMT [Median = 1.56; IQR = 0.70 versus Median = 0.94; IQR = 0.42; p = 0.009]. Patients with "acute culprit" carotid stenosis had a higher ipsilateral EMT [left ipsilateral EMT: Median = 1.46; IQR = 0.63; "non-acute": Median = 0.94; IQR = 0.43; p = 0.009; right ipsilateral EMT: Median = 2.25; IQR = 0.62; "non-acute": Median = 1.00; IQR = 0.51; p = 0.015]. This difference was not found in the contra-lateral EMT. Six months after the neurologic event, EMT ipsilateral to an "acute culprit" carotid stenosis decreased (p = 0.036). The amount of peri-carotid adipose tissue, estimated with EMT, was associated with atherosclerosis at the carotid arteries. The mean EMT was associated with the features of chronic atherosclerosis lesions: the presence of carotid plaques, IMT, and the area of the highest plaque. Ipsilateral EMT was linked with "acute culprit" atherosclerotic plaque.

Surgical approach for management of complete anterior capsular contraction syndrome.

Anterior capsular contraction syndrome is an uncommon but well-known complication associated with continuous curvilinear capsulorhexis performed during cataract surgery. It remains asymptomatic unless the constriction progresses to involve the visual axis or causes late intraocular lens-related complications. A male patient in his 50s presented with severely decreased vision in his right eye 2 years after uneventful cataract surgery. Slit-lamp biomicroscopy revealed capsular phimosis and a dense, central, fibrous plaque with total occlusion of the anterior capsulorhexis opening. Neodymium-doped yttrium aluminium garnet laser anterior capsulotomy and vitrectorhexis were attempted, but proved ineffective. Surgical excision with manual cutting of the fibrotic membrane was performed, successfully clearing the visual axis and restoring vision.