The additionally glycosylated variant of human sex hormone-binding globulin (SHBG) is linked to estrogen-dependence of breast cancer.

Summary Sex Hormone-Binding Globulin (SHBG), the plasma carrier for androgens and estradiol, inhibits the estradiolinduced proliferation of breast cancer cells through its membrane receptor, cAMP, and PKA. In addition, the SHBG membrane receptor is preferentially expressed in estrogen-dependent (ER+/PR+) breast cancers which are also characterized by a lower proliferative rate than tumors negative for the SHBG receptor. A variant SHBG with a point mutation in exon 8, causing an aminoacid substitution (Asp 327 → Asn) and thus, the introduction of an additional N-glycosylation site, has been reported. In this work, the distribution of the SHBG variant was studied in 255 breast cancer patients, 32 benign mammary disease patients, and 120 healthy women. The presence of the SHBG mutation was evaluated with PCR amplification of SHBG exon 8 and Hinf I restriction fragment length polymorphism (RFLP) procedure. This technique allowed us to identify 54 SHBG variants (53 W/v and 1 v/v) in breast cancer patients (21.2%), 5 variants (4 W/v and 1 v/v) in benign mammary disease patients (15.6%), and 14 variants (W/v) in the control group (11.6%). The results of PCR and RFLP were confirmed both by nucleotide sequence of SHBG exon 8 and western blot of the plasma SHBG. No differences in the mean plasma level of the protein were observed in the three populations. The frequency of the SHBG variant was significantly higher in ER+/PR+ tumors and in tumors diagnosed in patients over 50 years of age than in the control group. This observation suggests the existence of a close link between the estrogen-dependence of breast cancer and the additionally glycosylated SHBG, further supporting a critical role of the protein in the neoplasm

Official food safety audits in large scale retail trades in the time of COVID: system control experiences supported by an innovative approach

This work describes a new methodology used in large scale retail trades in official food safety auditing processes developed during COVID19 emergency. The aim is to evaluate Food Business Operators’ (FBOs) Food Safety Management System and its dynamic implementation and to understand the FBO’s level of cultural maturity about food safety according to EU Regulation 2021/382. The innovation mainly consists of: a) a pre-audit phase when auditors analyse food business operator’s (FBO) selfchecked plan and further documents to identify “markers” and useful evidences (that would be collected in on-site inspections) to evaluate the application of plan by FBO’s workers; b) an audit phase consisted of both a check of the company procedures and documents performed by the auditors via web conference and of contextually onsite inspections in a sample of company’s supermarkets performed by inspectors teams. The audit methodology here described may be useful, even though it is expensive in terms of time and energy used, for both Competent Authority (CA) and FBOs, regardless of the period of the COVID emergency. The so-structured official control allows the auditors to collect both documentary and on-site evidence at the same time, reaching a broader vision of auditees (not limited to single supermarkets) and a compliant with reality FBOs risk classification. The new approach may give advantages to both audit actors, CA as well as FBO, who may collect “markers” and evidence of the self-checked plan useful to improve FBO’s food safety system on the basis of the critical aspects detected during auditing process

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

Enforcement of the food hygiene package: role and requirements from a recent European Union Court’s judgement

Detection of non compliance with hygienic requirements is the major issue of a recent judgement of the Court of Justice of the European Union (CJEU). As long as the hygiene package addresses some obligation under condition as where necessary, if appropriate and similar, it is up to the official control to identify whether a infraction is at stake. In October 2011, the CJEU established the need of a correlation between the requirements regulated in the Annex of Regulation (EC) No. 852/2004 and Article 4(2) of the same regulation on one side, and the context of those provisions, on the other. By this way, the Court affirms that food business operators have to put adopt, implement and maintain a permanent procedure or procedures based on the Hazard Analysis Critical Control Point (HACCP) principles. Since hygienic requirements must be interpreted so as not to deprive Article 5 of the Reg. (EC) No. 852/2004 of effectiveness, it follows that when competent Authorities seemingly do not reckon actual contamination, one cannot conclude that a breach to law occurred on the basis of the find- ing that a potential purchaser could conceivably have touched foodstuff by hand or sneezed on it only. In such a case, competent Authority should take into consideration measures taken by those operators under Article 5 of the regulation in order to prevent, eliminate or reduce to acceptable levels the hazard inherent to the food process. This statement is of crucial importance since it requires a stronger effort by the official control in detecting violations to food law and gives room to a number of perspective shortcomings between EU food hygiene law and the Italian criminal food law

Enforcement of the food hygiene package: role and requirements from a recent European Union Court’s judgement

Detection of non compliance with hygienic requirements is the major issue of a recent judgement of the Court of Justice of the European Union (CJEU). As long as the hygiene package addresses some obligation under condition as where necessary, if appropriate and similar, it is up to the official control to identify whether a infraction is at stake. In October 2011, the CJEU established the need of a correlation between the requirements regulated in the Annex of Regulation (EC) No. 852/2004 and Article 4(2) of the same regulation on one side, and the context of those provisions, on the other. By this way, the Court affirms that food business operators have to put adopt, implement and maintain a permanent procedure or procedures based on the Hazard Analysis Critical Control Point (HACCP) principles. Since hygienic requirements must be interpreted so as not to deprive Article 5 of the Reg. (EC) No. 852/2004 of effectiveness, it follows that when competent Authorities seemingly do not reckon actual contamination, one cannot conclude that a breach to law occurred on the basis of the find- ing that a potential purchaser could conceivably have touched foodstuff by hand or sneezed on it only. In such a case, competent Authority should take into consideration measures taken by those operators under Article 5 of the regulation in order to prevent, eliminate or reduce to acceptable levels the hazard inherent to the food process. This statement is of crucial importance since it requires a stronger effort by the official control in detecting violations to food law and gives room to a number of perspective shortcomings between EU food hygiene law and the Italian criminal food law

A Genomic View of Estrogen Actions in Human Breast Cancer Cells by Expression Profiling of the Hormone Responsive Transcriptome.

Estrogen controls key cellular functions of responsive cells including the ability to survive, replicate, communicate and adapt to the extracellular milieu. Changes in the expression of 8400 genes were monitored here by cDNA microarray analysis during the first 32 h of human breast cancer (BC) ZR-75·1 cell stimulation with a mitogenic dose of 17 -estradiol, a timing which corresponds to completion of a full mitotic cycle in hormone-stimulated cells. Hierarchical clustering of 344 genes whose expression either increases or decreases significantly in response to estrogen reveals that the gene expression program activated by the hormone in these cells shows 8 main patterns of gene activation/inhibition. This newly identified estrogen-responsive transcriptome represents more than a simple cell cycle response, as only a few affected genes belong to the transcriptional program of the cell division cycle of eukaryotes, or showed a similar expression profile in other mitogen-stimulated human cells. Indeed, based on the functions assigned to the products of the genes they control, estrogen appears to affect several key features of BC cells, including their metabolic status, proliferation, survival, differentiation and resistance to stress and chemotherapy, as well as RNA and protein synthesis, maturation and turn-over rates. Interestingly, the estrogen-responsive transcriptome does not appear randomly interspersed in the genome. In chromosome 17, for example, a site particularly rich in genes activated by the hormone, physical association of co-regulated genes in clusters is evident in several instances, suggesting the likely existence of estrogen-responsive domains in the human genome