First paleoproteome study of fossil fish otoliths and the pristine preservation of the biomineral crystal host.

Otoliths are calcium carbonate components of the stato-acoustical organ responsible for hearing and maintenance of the body balance in teleost fish. During their formation, control over, e.g., morphology and carbonate polymorph is influenced by complex insoluble collagen-like protein and soluble non-collagenous protein assemblages; many of these proteins are incorporated into their aragonite crystal structure. However, in the fossil record these proteins are considered lost through diagenetic processes, hampering studies of past biomineralization mechanisms. Here we report the presence of 11 fish-specific proteins (and several isoforms) in Miocene (ca. 14.8-14.6 Ma) phycid hake otoliths. These fossil otoliths were preserved in water-impermeable clays and exhibit microscopic and crystallographic features indistinguishable from modern representatives, consistent with an exceptionally pristine state of preservation. Indeed, these fossil otoliths retain ca. 10% of the proteins sequenced from modern counterparts, including proteins specific to inner ear development, such as otolin-1-like proteins involved in the arrangement of the otoliths into the sensory epithelium and otogelin/otogelin-like proteins that are located in the acellular membranes of the inner ear in modern fish. The specificity of these proteins excludes the possibility of external contamination. Identification of a fraction of identical proteins in modern and fossil phycid hake otoliths implies a highly conserved inner ear biomineralization process through time.

Varicella zoster virus reactivation following COVID-19 vaccination: a report of 3 cases.

BACKGROUND: The advent of vaccination against COVID-19 brought great expectations for the control of the pandemic. As novel vaccines, much of the associated side effects were unknown. Currently, an increasing number of reports from side effects of COVID-19 vaccines have been published, namely on cutaneous reactions. These are of utmost importance to increase our knowledge about possible undesirable effects and its prevention. METHODS: We describe a series of 3 cases who presented with varicella zoster virus (VZV) reactivation following the first dose of 3 different COVID-19 vaccines. RESULTS: Three patients sought their Family Doctor after developing typical lesions of VZV reactivation, following a period of 3-13 days after COVID-19 vaccination. None was under immunosuppressive therapy. The 3 patients recovered in a few weeks and the subsequent doses of the vaccines were administered, without recurrence of the symptoms. CONCLUSIONS: These cases highlight the possibility of VZV reactivation after the first dose of COVID-19 vaccines. Family Doctors should be aware of this event and play an important role informing and reassuring local communities for this possible vaccine reaction.

Primary and secondary oocyte growth dynamics in anadromous semelparous Allis shad Alosa alosa.

We analysed the ovarian dynamics of the anadromous semelparous allis shad Alosa alosa for which our working hypothesis was that mature pre-spawning females would have very low or even exhausted primary growth (PG) oocyte reserves; semelparity has been linked with the depletion of the pool of PG oocytes. To test this hypothesis, the PG oocytes were enumerated, their recruitment pattern to the secondary growth (SG) phase was analysed and their potential replenishment from the pool of oogonia was examined in females caught very close to the Mondego River mouth, in central Portugal and along the river. The development of the SG oocytes was also analysed, the fecundity (batch, total and annual) values were estimated and the intensity of atresia was quantified. Ovarian samples and histological sections were investigated in parallel. A dynamic recruitment pattern of PG oocytes to the SG phase was revealed, where all PG oocytes were recruited and were not replenished by oogonia. Annual fecundity was subject to down-regulation due to atresia prior to spawning and its size was multiple times higher than the size of batch fecundity. Lack of population synchronicity in ovarian development and spawning migration was also observed. This multifaceted analysis of the ovarian dynamics of this species will contribute to management efforts for this critically endangered and economically important fish throughout its geographical distribution. The results reported in this study will also assist in unravelling the complexity of the early processes of oogenesis in fish.

Carbohydrates, glycemic index, glycemic load, and breast cancer risk: a systematic review and dose-response meta-analysis of prospective studies.

Context: The investigation of dose-response associations between carbohydrate intake, glycemic index, glycemic load, and risk of breast cancer stratified by menopausal status, hormone receptor status, and body mass index (BMI) remains inconclusive. Objective: A systematic review and dose-response meta-analyses was conducted to investigate these associations. Data Sources: As part of the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, PubMed was searched up to May 2015 for relevant studies on these associations. Study Selection: Prospective studies reporting associations between carbohydrate intake, glycemic index, or glycemic load and breast cancer risk were included. Data Extraction: Two investigators independently extracted data from included studies. Results: Random-effects models were used to summarize relative risks (RRs) and 95%CIs. Heterogeneity between subgroups, including menopausal status, hormone receptor status, and BMI was explored using meta-regression. Nineteen publications were included. The summary RRs (95%CIs) for breast cancer were 1.04 (1.00-1.07) per 10 units/d for glycemic index, 1.01 (0.98-1.04) per 50 units/d for glycemic load, and 1.00 (0.96-1.05) per 50 g/d for carbohydrate intake. For glycemic index, the association appeared slightly stronger among postmenopausal women (summary RR per 10 units/d, 1.06; 95%CI, 1.02-1.10) than among premenopausal women, though the difference was not statistically significant (Pheterogeneity = 0.15). Glycemic load and carbohydrate intake were positively associated with breast cancer among postmenopausal women with estrogen-negative tumors (summary RR for glycemic load, 1.28; 95%CI, 1.08-1.52; and summary RR for carbohydrates, 1.13; 95%CI, 1.02-1.25). No differences in BMI were detected. Conclusions: Menopausal and hormone receptor status, but not BMI, might be potential influencing factors for the associations between carbohydrate intake, glycemic index, glycemic load, and breast cancer.

B-cell phenotype and IgD-CD27- memory B cells are affected by TNF-inhibitors and tocilizumab treatment in rheumatoid arthritis.

BACKGROUND: The use of TNF-inhibitors and/or the IL-6 receptor antagonist, tocilizumab, in rheumatoid arthritis (RA) have pleiotropic effects that also involve circulating B-cells. The main goal of this study was to assess the effect of TNF-inhibitors and tocilizumab on B-cell phenotype and gene expression in RA. METHODS: Blood samples were collected from untreated early RA (ERA) patients, established RA patients under methotrexate treatment, established RA patients before and after treatment with TNF-inhibitors and tocilizumab, and healthy donors. B-cell subpopulations were characterized by flow cytometry and B-cell gene expression was analyzed by real-time PCR on isolated B-cells. Serum levels of BAFF, CXCL13 and sCD23 were determined by ELISA. RESULTS: The frequency of total CD19+ B cells in circulation was similar between controls and all RA groups, irrespective of treatment, but double negative (DN) IgD-CD27- memory B cells were significantly increased in ERA and established RA when compared to controls. Treatment with TNF-inhibitors and tocilizumab restored the frequency of IgD-CD27- B-cells to normal levels, but did not affect other B cell subpopulations. TACI, CD95, CD5, HLA-DR and TLR9 expression on B-cells significantly increased after treatment with either TNF-inhibitors and/ or tocilizumab, but no significant changes were observed in BAFF-R, BCMA, CD69, CD86, CXCR5, CD23, CD38 and IgM expression on B-cells when comparing baseline with post-treatment follow-ups. Alterations in B-cell gene expression of BAFF-R, TACI, TLR9, FcγRIIB, BCL-2, BLIMP-1 and ß2M were found in ERA and established RA patients, but no significant differences were observed after TNF-inhibitors and tocilizumab treatment when comparing baseline and follow-ups. Serum levels of CXCL13, sCD23 and BAFF were not significantly affected by treatment with TNF-inhibitors and tocilizumab. CONCLUSIONS: In RA patients, the use of TNF-inhibitors and/ or tocilizumab treatment affects B-cell phenotype and IgD-CD27- memory B cells in circulation, but not B-cell gene expression levels.

An update of the WCRF/AICR systematic literature review on esophageal and gastric cancers and citrus fruits intake.

PURPOSE: The 2007 World Cancer Research Fund/American Institute for Cancer Research expert report concluded that foods containing vitamin C probably protect against esophageal cancer and fruits probably protect against gastric cancer. Most of the previous evidence was from case-control studies, which may be affected by recall and selection biases. More recently, several cohort studies have examined these associations. We conducted a systematic literature review of prospective studies on citrus fruits intake and risk of esophageal and gastric cancers. METHODS: PubMed was searched for studies published until 1 March 2016. We calculated summary relative risks and 95 % confidence intervals (95 % CI) using random-effects models. RESULTS: With each 100 g/day increase of citrus fruits intake, a marginally significant decreased risk of esophageal cancer was observed (summary RR 0.86, 95 % CI 0.74-1.00, 1,057 cases, six studies). The associations were similar for squamous cell carcinoma (RR 0.87, 95 % CI 0.69-1.08, three studies) and esophageal adenocarcinoma (RR 0.93, 95 % CI 0.78-1.11, three studies). For gastric cancer, the nonsignificant inverse association was observed for gastric cardia cancer (RR 0.75, 95 % CI 0.55-1.01, three studies), but not for gastric non-cardia cancer (RR 1.02, 95 % CI 0.90-1.16, four studies). Consistent summary inverse associations were observed when comparing the highest with lowest intake, with statistically significant associations for esophageal (RR 0.77, 95 % CI 0.64-0.91, seven studies) and gastric cardia cancers (RR 0.62, 95 % CI 0.39-0.99, three studies). CONCLUSIONS: Citrus fruits may decrease the risk of esophageal and gastric cardia cancers, but further studies are needed.

Fruits, vegetables, and bladder cancer risk: a systematic review and meta-analysis.

Smoking is estimated to cause about half of all bladder cancer cases. Case-control studies have provided evidence of an inverse association between fruit and vegetable intake and bladder cancer risk. As part of the World Cancer Research/American Institute for Cancer Research Continuous Update Project, we conducted a systematic review and meta-analysis of prospective studies to assess the dose-response relationship between fruit and vegetables and incidence and mortality of bladder cancer. We searched PubMed up to December 2013 for relevant prospective studies. We conducted highest compared with lowest meta-analyses and dose-response meta-analyses using random effects models to estimate summary relative risks (RRs) and 95% confidence intervals (CIs), and used restricted cubic splines to examine possible nonlinear associations. Fifteen prospective studies were included in the review. The summary RR for an increase of 1 serving/day (80 g) were 0.97 (95% CI: 0.95-0.99) I(2)  = 0%, eight studies for fruits and vegetables, 0.97 (95% CI: 0.94-1.00, I(2)  = 10%, 10 studies) for vegetables and 0.98 (95% CI: 0.96-1.00, I(2)  = 0%, 12 studies) for fruits. Results were similar in men and women and in current, former and nonsmokers. Amongst fruits and vegetables subgroups, for citrus fruits the summary RR for the highest compared with the lowest intake was 0.87 (95% CI: 0.76-0.99, I(2)  = 0%, eight studies) and for cruciferous vegetables there was evidence of a nonlinear relationship (P = 0.001). The current evidence from cohort studies is not consistent with a role for fruits and vegetables in preventing bladder cancer.

Quantitation of methylxanthinic alkaloids and phenolic compounds in mate (Ilex paraguariensis) and their effects on blood vessel formation in chick embryos.

Methylxanthinic alkaloids and phenolic compounds are related to the therapeutic properties of Ilex paraguariensis infusions. Considering the known vascular tropism of xanthines, an aqueous extract (mate) and caffeine were evaluated on blood vessel formation, in connection with the analysis of those secondary metabolites, which was performed in young and mature leaf samples collected in three cultivation systems located in the southern region in Brazil (Santa Catarina State). Samples of young and mature leaves from a monoculture cultivation system (MC) showed the highest content of phenolic compounds (149.68 microg/mL, young leaves; 135.50 microg/mL, mature leaves) and caffeine (young leaves, 148.07 microg/mL; mature leaves, 244.63 microg/mL) as compared to samples from agroforesty (AF) and shaded-native (NT) cultures. Theophylline was not detected in samples by reverse phase-high performance liquid chromatography, and mature leaves showed lower theobromine amounts (11.46 microg/mL). Treatments performed with mate aqueous extract and caffeine (1.03-4.12 microM/disk) in the yolk sac vascular membranes of 2-day-old chick embryos revealed pro-vasculo- and angiogenic properties as well as embryonic growth enhancement. These findings, uncoupled from any detectable embryotoxic effect, suggest a potential therapeutic and/or prophylactic use in cardiovascular disorders for caffeine and related constituents of mate plant extracts, an issue that waits further studies.