Harvesting the Power of Green Synthesis: Gold Nanoparticles Tailored for Prostate Cancer Therapy.

Biosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing bio-compatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been explored, there is a limited body of research focusing on the crucial physicochemical conditions influencing bAuNP production. In this study, we aim to identify the optimal growth phase of Pseudomonas aeruginosa cultures that maximizes the redox potential and coordinates the formation of bAuNPs with increased efficiency. The investigation employs 2,6-dichlorophenolindophenol (DCIP) as a redox indicator. Simultaneously, we explore the impact of temperature, pH, and incubation duration on the biosynthesis of bAuNPs, with a specific emphasis on their potential application as antitumor agents. Characterization of the resulting bAuNPs is conducted using ATR-FT-IR, TEM, and UV-Vis spectroscopy. To gain insights into the anticancer potential of bAuNPs, an experimental model is employed, utilizing both non-neoplastic (HPEpiC) and neoplastic (PC3) epithelial cell lines. Notably, P. aeruginosa cultures at 9 h/OD600 = 1, combined with biosynthesis at pH 9.0 for 24 h at 58 °C, produce bAuNPs that exhibit smaller, more spherical, and less aggregated characteristics. Crucially, these nanoparticles demonstrate negligible effects on HPEpiC cells while significantly impacting PC3 cells, resulting in reduced viability, migration, and lower IL-6 levels. This research lays the groundwork for the development of more specialized, economical, and ecologically friendly treatment modalities.

Unveiling the Path to Resilience: Prioritizing Mental Health, Sleep, and Nutrition in the Post-COVID Era.

The COVID-19 pandemic has disrupted daily life, impacting relationships, work, and education. This has led to increased stress, anxiety, and depression, along with altered sleep patterns and eating behaviors. Quarantine and isolation have worsened mental health, especially in children and the elderly, due to the loss of activities and physical contact. Sleep disorders and negative dreams perpetuate poor sleep quality, increasing the risk of health issues. Sedentary lifestyles and emotional effects contribute to unhealthy eating patterns and obesity, exacerbated by disrupted routines and limited outdoor activities. Addressing these challenges requires prioritizing mental health, promoting healthy sleep habits, and addressing obesity factors. The pandemic has profoundly affected human well-being, but resilience, mental health, sleep, and nutrition can enhance overall well-being and adaptability in the post-COVID era. This comprehensive opinion aims to raise awareness of the wide-ranging impacts of this pandemic on various aspects of human well-being and to emphasize the importance of implementing strategies that prioritize mental health, improve sleep habits, address eating behaviors, and foster resilience to navigate and thrive in the face of future challenges.

Associations between muscle mass, strength, and performance and non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a rising global health issue. The influence of muscle in its pathophysiology has recently gained attention. Our aim was to investigate the association of low muscle mass, strength, and performance with the presence and severity of NAFLD. METHODS: Patients with metabolic syndrome followed in an outpatient clinic, were consecutively included, between April 1st and December 31st, 2019. Abdominal ultrasound for the diagnosis of NAFLD, NAFLD fibrosis score (NFS) and Fibrosis-4 Index (FIB-4) for determination of significant fibrosis, dual-energy X-ray absorptiometry for calculation of skeletal muscle index (SMI = appendicular skeletal mass / weight x100) and sarcopenic index (SI = appendicular skeletal mass / Body Mass Index), and the Short Physical Performance Battery for muscle strength and performance assessment were performed. Sarcopenia was defined as low muscle strength and low SMI or SI. RESULTS: A total of 157 patients were included, of which 68.8% had NAFLD, 66.2% low SMI, 50.3% low SI, 16.6% low performance and 11.5% low strength. In patients with NAFLD, prevalence of significant fibrosis by NFS was 15.7%. Low SMI was associated with presence of NAFLD when adjusted for age, sex, type 2 diabetes mellitus, hypertension, and dyslipidemia, but not for body mass index and waist circumference. Low SMI, low SI, and sarcopenia were associated with significant fibrosis in univariate analysis; the small number of events precluded a multivariable analysis. CONCLUSIONS: Low SMI was associated with NAFLD independently of demographics and comorbidities but not of other parameters of body composition. This contrasts with most studies published on this matter.

Characterizing palliative care needs in people with or at risk of developing diabetic foot ulcers.

Aims: Diabetic foot ulcers (DFUs) have a significant impact on a patient's quality of life and life expectancy, with mortality rates comparable with malignant diseases. However, there is a lack of data regarding palliative care needs in this population. We aimed to characterize palliative care needs in people under diabetic foot surveillance using the Integrated Palliative care Outcome Scale (IPOS) and EuroQol-5D three-level version (EQ-5D-3L) and to assess differences between those with and without a DFU. Methods: We conducted a cross-sectional study with consecutive sampling inclusion of patients followed in a tertiary hospital's Diabetic Foot Clinic between February and October 2019 with (n = 20) and without (n = 42) active DFU. Results: The most frequent symptoms encountered were pain, weakness or lack of energy, sore or dry mouth and drowsiness. Patients with an active DFU were significantly more likely to report feeling anxious or worried in comparison with those without (95% versus 55%, p = 0.002). Only 10% of the participants with an active DFU said that they were always able to share how they felt with family and friends as much as they wanted in comparison with 45% of those without (p = 0.006). Conclusion: Our study identified palliative care needs in patients under diabetic foot surveillance with and without DFU, including a significant presence of physical symptoms. Patients in both groups showed signs of emotional/psychological distress, with a higher manifestation in patients with DFU. To the best of our knowledge, this is the first study addressing and characterizing palliative care needs in this population.

Enhanced 3T3-L1 Differentiation into Adipocytes by Pioglitazone Pharmacological Activation of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-γ).

Despite the primary function of pioglitazone in antidiabetic treatment, this drug is a potent inducer of PPAR-γ, a crucial receptor that is involved in adipocyte differentiation. In this work, we propose an optimized methodology to enhance the differentiation of 3T3-L1 fibroblasts into adipocytes. This process is crucial for adipocyte secretome release, which is fundamental for understanding the molecular mechanisms that are involved in obesity for in vitro studies. To achieve this, a pioglitazone dose-response assay was determined over a range varying from 0 to 10 µM. Lipid accumulation was evaluated using Oil-Red-O. The results showed that 10 µM pioglitazone enhanced differentiation and increased secretome production. This secretome was then added into two cell lines: PC3 and RAW264.7. In the PC3 cells, an increase of aggressiveness was observed in terms of viability and proliferation, with the increase of anti-inflammatory cytokines. Conversely, in RAW264.7 cells, a reduction of viability and proliferation was observed, with a decrease in the overexpression of pro-inflammatory cytokines. Overall, the present work constitutes an improved method for adipocyte secretome production that is suitable for experimental biology studies and that could help with our understanding of the molecular mechanisms underlying adiposity influence in other cells.

Noninvasive fibrosis tools in NAFLD: validation of APRI, BARD, FIB-4, NAFLD fibrosis score, and Hepamet fibrosis score in a Portuguese population.

OBJECTIVES: The burden of nonalcoholic fatty liver disease (NAFLD) is increasing, with an estimated prevalence in Europe of 20-30%. Although most patients present with simple steatosis, some progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Definite diagnosis and staging require liver biopsy, which is not feasible given the high prevalence of NAFLD. As such, several noninvasive tools have been formulated. However, to date, none have been validated in the Portuguese population. The aim of this study was to determine the diagnostic accuracy of the aspartate aminotransferase to platelet ratio (APRI), the BMI, AST/ALT ratio and Diabetes (BARD), the FIB-4 Index (FIB-4), the Hepamet fibrosis score (HFS), and the NAFLD fibrosis score (NFS) in a Portuguese population. METHODS: A retrospective review of liver biopsies from two hospital centers was performed. Patients with NAFLD and no decompensated cirrhosis, liver cancer, or terminal illness were included. APRI, BARD, FIB-4, HFS, and NFS were calculated for each patient. RESULTS: A total of 121 individuals were included, of which 21.5% had advanced fibrosis (F ≥ 3). There was a moderate or high correlation between most tools. The negative predictive factor (NPV) and area under receiver operating curve (AUROC) were 89.9% and 0.80 for APRI, 91.8% and 0.84 for BARD, 95.7% and 0.88 for FIB-4, 96.4% and 0.88 for HFS, and 93.0% and 0.86 for NFS, respectively. CONCLUSION: The tools analyzed had excellent performance (AUROC ≥ 0.80) and were adequate for ruling out advanced fibrosis (NPV ≥ 89.9%) in a Portuguese population. As such, they are adequate for use in clinical practice or as a part of referral and follow-up programs wherever this population is treated. ABBREVIATIONS: APRI - aspartate aminotransferase to platelet ratio, ALT - alanine aminotransferase, AST - aspartate aminotransferase, BARD - BMI, AST/ALT ratio and Diabetes, BMI - body mass index, FIB-4 - FIB-4 index, HCC - hepatocellular carcinoma, HFS - Hepamet fibrosis score, HOMA-IR - homeostatic model assessment for insulin resistance, IQR - interquartile range, MAFLD - metabolic associated fatty liver disease, NAFLD - nonalcoholic fatty liver disease, NASH - nonalcoholic steatohepatitis, NFS - NAFLD fibrosis score, OMIC - genomics, transcriptomics, proteomics, and metabolomics, T2DM - type 2 diabetes mellitus.

Investigating Febrile Polyserositis: An Unusual Case of Idiopathic Hypereosinophilic Syndrome.

Hypereosinophilic syndrome (HES) is a heterogenous group of diseases characterized by abnormal accumulation of eosinophils in the blood or peripheral tissues. It can affect all organs and therefore clinical manifestations are highly variable. We describe the case of a 38-year-old man admitted for febrile polyserositis. He developed cardiac tamponade requiring pericardiocentesis complicated by left ventricle perforation which was successfully repaired. He presented mild peripheral eosinophilia. Bronchoalveolar lavage evidenced eosinophilic alveolitis, and pleural and pericardium histopathology revealed the presence of abundant eosinophils. All other causes of tissue eosinophilia were excluded and the diagnosis of idiopathic HES was made. The patient was started on glucocorticoids with resolution of symptoms. This case report describes a rare but potentially fatal presentation of HES and demonstrates the difficulty and delay in diagnosis when peripheral hypereosinophilia is absent. LEARNING POINTS: Hypereosinophilic syndrome (HES) is characterized by abnormal accumulation of eosinophils in the blood or peripheral tissues.The clinical manifestations of HES are highly variable.It may be difficult to diagnose HES when peripheral hypereosinophilia is absent.

Characterization of the Oral Microbiome of Medicated Type-2 Diabetes Patients.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is becoming a significant global health care problem. Several studies have shown that people with diabetes are more susceptible to oral problems, such as periodontitis and, although the causes are still inconclusive, oral microbiota is considered to play a major role in oral health. This study aimed to characterize the oral microbiome of a sample representing T2DM patients from Portugal and exploit potential associations between some microorganisms and variables like teeth brushing, smoking habits, average blood sugar levels, medication and nutrient intake. By sequencing the hypervariable regions V3-V4 of the 16S rRNA gene in 50 individuals belonging to a group of diabetes patients and a control group, we found a total of 232 taxa, from which only 65% were shared between both groups. No differences were found in terms of alpha and beta diversity between categories. We did not find significant differences in the oral microbiome profiles of control and diabetes patients. Only the class Synergistia and the genus TG5, which are related to periodontitis, were statistically more frequent in the control group. The similar microbiome profiles of medicated diabetics and the control group indicates that the relationship between the T2DM and the oral microbiome might be more related to either the lifestyle/diet rather than diabetes per se. Moreover, this study provides, for the first time, insights into the oral microbiome of a population with a high prevalence of diabetes.

Prehospital Anticholinergic Burden Is Associated With Delirium but Not With Mortality in a Population of Acutely Ill Medical Patients.

OBJECTIVES: Anticholinergic drugs have several side effects, and they have been associated with adverse outcomes, particularly in older patients. The aim of this study was to analyze anticholinergic burden and its relationship to delirium and mortality in older acutely ill medical patients. DESIGN: Cohort study. SETTING AND PARTICIPANTS: Patients 65 years of age and older who were admitted to an Internal Medicine ward between August 1 and December 31, 2016. METHODS: Anticholinergic drug use, outpatient and inpatient, was assessed using the Anticholinergic Cognitive Burden Scale (ACB). Prevalent delirium was diagnosed by the Short Confusion Assessment Method (Short-CAM). RESULTS: Of the 198 patients, 28.3% developed delirium. Mortality rate was 13.6% in-hospital and 45.6% at 12 months. In multivariate analysis, outpatient ACB was associated with delirium, with an odds ratio (OR) of 1.65 [95% confidence interval (CI) 1.09-2.51]. Those with delirium had longer hospital stays (median 13 vs 8 days; P = .01), received more drugs (median 18 vs 15; P = .02), and presented a higher inpatient ACB (mean 3.9 vs 3.1; P = .034). No increased risk was found for in-hospital or 12-month mortality with drug use, ACB, or delirium. DISCUSSION: In the population studied, we found an association between anticholinergic burden as measured by the ACB and the presence of delirium, but not with mortality at 12 months. A very high 12-month mortality rate might have been an obstacle for association recognition. CONCLUSIONS AND IMPLICATIONS: Clinician awareness of possible drug side effects, especially in older populations, is crucial. As part of medication reconciliation at the time of hospitalization, ACB of prehospitalization medications should be routinely calculated by inpatient pharmacy services and made available to medical teams.

Porphyrias: A clinically based approach.

BACKGROUND: Porphyrias are a group of metabolic diseases, individually rare but with an important combined prevalence. Because of their pathological complexity and clinical heterogeneity, they present a challenging diagnosis. The present review aims to provide a clinically based approach to the recognition and treatment of these disorders. METHODS: We carried out a search in PubMed, with the keyword "porphyria", for reviews published in English from 2010 until 2017. RESULTS: The research yielded 196 papers, of which 64 were included in the final narrative review. CONCLUSIONS: Porphyrias can be divided based on clinical presentation in acute neurovisceral, chronic cutaneous bullous, chronic cutaneous non-bullous and acute neurovisceral/chronic cutaneous bullous. Each individual porphyria presents a characteristic pattern of porphyrins in plasma, urine, stool and red blood cells. As such, diagnosis is easily obtained by following a simple diagnostic algorithm. Early recognition is key in managing these diseases. Neurovisceral porphyrias require acute support therapy and chronic eviction of precipitating factors. Cutaneous prophyrias, as photosensitivity disorders, rely on sunlight avoidance and, in some cases, specific therapeutic interventions. Given the rarity of these conditions, physician awareness is crucial.

Lower-limb amputation following foot ulcers in patients with diabetes: classification systems, external validation and comparative analysis.

BACKGROUND: This study aimed to validate and compare the existing systems developed to stratify subjects with diabetic foot ulcers by risk of consequent lower extremity amputation. METHODS: We conducted a prospective cohort study on a consecutive series of patients (mean age of 68 years; 64% male) with active ulcer who were attending our Hospital Diabetic Foot Clinic (n = 293) from January 2010 to March 2013. At baseline, we collected information on the participants' characteristics and the relevant variables. Afterwards, we assessed the predictive value of each variable and each system's prognostic accuracy for amputation occurrence. RESULTS: During a median follow-up of 91 days (interquartile range of 98), ulcers healed in 62% of the subjects. Major amputation occurred in 7% and minor occurred in 17%. Previous ulcer or amputation, ulcer area, and gangrene were associated with amputation occurrence. Nephropathy, pulses number, ulcer aetiology, depth, and number were associated with risk of amputation. Systems typically presented sensitivity values ≥80% and negative likelihood ratios ≤0.5 for the highest risk group; area under the receiver operating characteristic curve ranged from 0.56 to 0.83 and positive likelihood ratios from 1.0 to 5.9. If one chose only major amputation as an outcome, positive predictive values were lower, and negative predictive values tended to be higher. CONCLUSIONS: System stages, grades, scores, and/or prognostics were generally associated with amputation, presenting overall substantial accuracy values. Nevertheless, great improvement is possible. A multicentre study validating and refining the existing systems is needed to improve clinical decision-making in this area.

The independent contribution of diabetic foot ulcer on lower extremity amputation and mortality risk.

AIMS: To estimate 3-year risk for diabetic foot ulcer (DFU), lower extremity amputation (LEA) and death; determine predictive variables and assess derived models accuracy. MATERIAL AND METHODS: Retrospective cohort study including all subjects with diabetes enrolled in our diabetic foot outpatient clinic from beginning 2002 until middle 2010. Data were collected from clinical records. RESULTS: 644 subjects with mean age of 65.1 (±11.2) and diabetes duration of 16.1 (±10.8) years. Cumulative incidence was 26.6% for DFU, 5.8% for LEA and 14.0% for death. In multivariate analysis, physical impairment, peripheral arterial disease complication history, complication count and previous DFU were associated with DFU; complication count, foot pulses and previous DFU with LEA and age, complication count and previous DFU with death. Predictive models' areas under the ROC curves ranged from 0.80 to 0.83. A simplified model including previous DFU and complication count presented high accuracy. Previous DFU was associated with all outcomes, even when adjusted for complication count, in addition to more complex models. CONCLUSIONS: DFU seems more than a marker of complication status, having independent impact on LEA and mortality risk. Proposed models may be applicable in healthcare settings to identify patients at higher risk of DFU, LEA and death.