Ranibizumab combined with low-dose sorafenib for exudative age-related macular degeneration

Angiogenesis is a common factor in the pathogenesis of cancer and in exudative age-related macular degeneration (AMD). Therefore, angiogenesis inhibition has been developed as a therapeutic strategy. We report 2 cases of recurrent exudative AMD in which oral sorafenib, a tyrosine kinase inhibitor approved for cancer, was added to intravitreal ranibizumab, an antibody to vascular endothelial growth factor. These 2 patients were followed up by determination of visual acuity, fluorescein angiography, fundoscopy, and optical coherence tomography. The visual acuity of 1 patient improved from 20/70 to 20/60 while he was receiving sorafenib therapy; that of the other did not. Marked improvement was noted in both patients on optical coherence tomography. Additionally, both patients appeared to receive some benefit when low-dose oral sorafenib was used as monotherapy after its initial addition to ranibizumab therapy. Randomized trials of adding sorafenib to standard therapy for patients with neovascular AMD should be considered.     

Diet and SIRT1 Genotype Interact to Modulate Aging-Related Processes in Patients with Coronary Heart Disease: From the CORDIOPREV Study

We investigated whether long-term consumption of two healthy diets (low-fat (LF) or Mediterranean (Med)) interacts with SIRT1 genotypes to modulate aging-related processes such as leucocyte telomere length (LTL), oxidative stress (OxS) and inflammation in patients with coronary heart disease (CHD). LTL, inflammation, OxS markers (at baseline and after 4 years of follow-up) and SIRT1-Single Nucleotide Polymorphisms (SNPs) (rs7069102 and rs1885472) were determined in patients from the CORDIOPREV study. We analyzed the genotype-marker interactions and the effect of diet on these interactions. Regardless of the diet, we observed LTL maintenance in GG-carriers for the rs7069102, in contrast to carriers of the minor C allele, where it decreased after follow-up (p = 0.001). The GG-carriers showed an increase in reduced/oxidized glutathione (GSH/GSSG) ratio (p = 0.003), lower lipid peroxidation products (LPO) levels (p < 0.001) and a greater decrease in tumor necrosis factor-alpha (TNF-α) levels (p < 0.001) after follow-up. After the LF diet intervention, the GG-carriers showed stabilization in LTL which was significant compared to the C allele subjects (p = 0.037), although the protective effects found for inflammation and OxS markers remained significant after follow-up with the two diets. Patients who are homozygous for the SIRT1-SNP rs7069102 (the most common genotype) may benefit from healthy diets, as suggested by improvements in OxS and inflammation in patients with CHD, which may indicate the slowing-down of the aging process and its related diseases.     

The Relationship between Serum Adipokines,miR-222-3p,miR-103a-3p and Glucose Regulation in Pregnancy and Two to Three Years Post-Delivery in Women with Gestational Diabetes Mellitus Adhering to Mediterranean Diet Recommendations

The San Carlos Gestational Diabetes Mellitus (GDM) prevention study, a nutritional intervention RCT based on a Mediterranean Diet (MedDiet), has been shown to reduce the incidence of GDM. The objective of this study is to investigate the relationship of leptin, adiponectin, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), insulin and HOMA-IRand circulating miRNAs (miR-29a-3p, miR-103a-3p, miR-132-3p, miR-222-3p) with the appearance of GDM and with MedDiet-based nutritional intervention, at 24–28 gestational weeks (GW), and in glucose regulation 2–3 years post-delivery (PD). A total of 313 pregnant women, 77 with GDM vs. 236 with normal glucose tolerance (NGT), 141 from the control group (CG, MedDiet restricting the consumption of dietary fat including EVOO and nuts during pregnancy) vs. 172 from the intervention group (IG, MedDiet supplemented with extra virgin olive oil (EVOO) and pistachios during pregnancy) were compared at Visit 1 (8–12 GW), Visit 2 (24–28 GW) and Visit 3 (2–3 years PD). Expression of miRNAs was determined by the Exiqon miRCURY LNA RT-PCR system. Leptin, adiponectin, IL-6 and TNF-α, were measured by Milliplex^® immunoassays on Luminex 200 and insulin by RIA. Women with GDM vs. NTG had significantly higher leptin median (Q1–Q3) levels (14.6 (9.2–19.4) vs. 9.6 (6.0–15.1) ng/mL; p < 0.05) and insulin levels (11.4 (8.6–16.5) vs. 9.4 (7.0–12.8) µUI/mL; p < 0.001) and lower adiponectin (12.9 (9.8–17.2) vs. 17.0 (13.3–22.4) µg/mL; p < 0.001) at Visit 2. These findings persisted in Visit 3, with overexpression of miR-222-3p (1.45 (0.76–2.21) vs. 0.99 (0.21–1.70); p < 0.05)) and higher levels of Il-6 and TNF-α. When the IG is compared with the CG lower levels of insulin, HOMA-IR-IR, IL-6 levels at Visit 2 and 3 and leptin levels only at Visit 2 were observed. An overexpression of miR-222-3p and miR-103a-3p were also observed in IG at Visit 2 and 3. The miR-222-3p and miR103a-3p expression correlated with insulin levels, HOMA-IR, IL-6 and TNF-α at Visit 2 (all p < 0.05). These data support the association of leptin, adiponectin and insulin/HOMA-IR with GDM, as well as the association of insulin/HOMA-IR and IL-6 and miR-222-3p and miR-103a-3p expression with a MedDiet-based nutritional intervention.     

Beetroot Juice Produces Changes in Heart Rate Variability and Reduces Internal Load during Resistance Training in Men: A Randomized Double-Blind Crossover

Beetroot juice (BJ) has been used as a sport supplement, improving performance in resistance training (RT). However, its effect on the modulation of the autonomic nervous system has not yet been widely studied. Therefore, the objective of this randomized double-blind crossover study was to assess the effect of acute BJ supplementation compared to placebo in blood pressure (BP), heart rate (HR), heart rate variability (HRV) and internal load during RT measure as Root Mean Square of the Successive Differences between adjacent RR intervals Slope (RMSSD and RMSSD-Slope, respectively). Eleven men performed an incremental RT test (three sets at 60%, 70% and 80% of their repetition maximum) composed by back squat and bench press with. HR, HRV and RMSSD-Slope were measured during and post exercise. As the main results, RMSSD during exercise decrease in the BJ group compared to placebo (p = 0.023; ES = 0.999), there were no differences in RMSSD post-exercise, and there were differences in RMSSD-Slope between groups in favor of the BJ group (p = 0.025; ES = 1.104) with a lower internal load. In conclusion, BJ supplementation seems to be a valuable tool for the reduction in the internal load of exercise during RT measured as RMSSD-Slope while enhancing performance.     

How has the COVID-19 pandemic influenced prostate cancer?—a tertiary single-centre analysis of oncological results,diagnosis and treatment times

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has affected care for diseases like cancer. The aim was to evaluate the impact of COVID-19 on waiting times for diagnosis and treatment of prostate cancer (PC), as well as the possible effect on the treatment results in PC patients undergoing radical prostatectomy.MethodsWe compared the results of 497 patients who underwent biopsy prior to the COVID-19 pandemic (1 January–31 December 2019) with those of 290 patients biopsied during the COVID-19 pandemic (1 January–31 December 2020). Demographic data, tumour characteristics, type of treatment and diagnosis times were comparable. Prostate specific antigen (PSA) levels were recorded at consultation prior to biopsy and after treatment. Mann-Whitney and chi-square tests were used to compare continuous variables and percentages, respectively.ResultsIn 2020, there were fewer urology consultations (35,160 vs. 40,225 in 2019). The median PSA in 2020 was significantly higher (14.3 vs. 9.9 ng/dL in 2019). In 2019, 53.1% (N=264) of the biopsies were positive for cancer vs. 47.2% (N=137) in 2020 (P=0.104). In 2020, more patients presented with metastatic disease (7.3% vs. 1.9%, P=0.009). Also, in 2020 there was a longer waiting time for prostate biopsy (42.1 vs. 35.3 days in 2019, P=0.019). A total of 132 patients underwent laparoscopic radical prostatectomy (LARP). The median time until surgery was similar in both years (71.9 vs. 58.29 days). During 2020, a higher percentage of patients had ISUP grade 4 in the surgical specimen (34.3% vs. 17.5%, P=0.07). Furthermore, a higher percentage of aggressive (pT3) tumours were diagnosed (37.2% vs. 27.2%, P=0.08), and the percentage of patients with involvement of surgical margins was also higher (48.6% vs. 29.3%, P=0.027). There were no differences between the groups in terms of biochemical recurrence or persistent PSA at one year (P=0.711).ConclusionsDelayed biopsy during the COVID-19 period did not appear to adversely impact biopsy results. Patients biopsied in 2020 had higher PSA, possibly due to proper triaging. A higher rate of adverse pathology outcomes was observed in patients undergoing radical prostatectomy during the pandemic, probably due to understaging of the biopsy. This study serves to raise awareness of the risk of deterioration of care of PC patients due to possible underdiagnosis.     

Magnetic Phase Diagram of van der Waals Antiferromagnet TbTe3

Terbium tritelluride, TbTe₃, orders antiferromagnetically in three steps at T_N1 = 6.7 K, T_N2 = 5.7 K, and T_N3 = 5.4 K, preceded by a correlation hump in magnetic susceptibility at T* ~8 K. Combining thermodynamic, i.e., specific heat C_p and magnetization M, and transport, i.e., resistance R, measurements we established the boundaries of two commensurate and one charge density wave modulated phases in a magnetic field oriented along principal crystallographic axes. Based on these measurements, the magnetic phase diagrams of TbTe₃ at H‖a, H‖b and H‖c were constructed.     

Multiple Mutations Associated with Emergent Variants Can Be Detected as Low-Frequency Mutations in Early SARS-CoV-2 Pandemic Clinical Samples

Genetic analysis of intra-host viral populations provides unique insight into pre-emergent mutations that may contribute to the genotype of future variants. Clinical samples positive for SARS-CoV-2 collected in California during the first months of the pandemic were sequenced to define the dynamics of mutation emergence as the virus became established in the state. Deep sequencing of 90 nasopharyngeal samples showed that many mutations associated with the establishment of SARS-CoV-2 globally were present at varying frequencies in a majority of the samples, even those collected as the virus was first detected in the US. A subset of mutations that emerged months later in consensus sequences were detected as subconsensus members of intra-host populations. Spike mutations P681H, H655Y, and V1104L were detected prior to emergence in variant genotypes, mutations were detected at multiple positions within the furin cleavage site, and pre-emergent mutations were identified in the nucleocapsid and the envelope genes. Because many of the samples had a very high depth of coverage, a bioinformatics pipeline, “Mappgene”, was established that uses both iVar and LoFreq variant calling to enable identification of very low-frequency variants. This enabled detection of a spike protein deletion present in many samples at low frequency and associated with a variant of concern.