Food Security and Foodborne Mycotoxicoses-What Should Be the Adequate Risk Assessment and Regulation?

The purpose of this review is to elucidate the actual threat of the most prevalent mycotoxins in agricultural commodities and human/animal food/feed for the induction of foodborne diseases or ailments. The underestimated hazard of combined mycotoxin uptake by animals or humans is critically discussed with regard to synergistic or additive interaction between some target mycotoxins. The real toxicity of target mycotoxin combinations as it happens in practice is evaluated and possible lower limit values or control measures are suggested in such cases.

Natural feed additives and bioactive supplements versus chemical additives as a safe and practical approach to combat foodborne mycotoxicoses.

This review highlights the possible hazard of mycotoxins occurrence in foods and feeds in regards to foodborne diseases. The possible management of the risk of contamination of foods and feeds with mycotoxins by using natural feed additives, protecting against deleterious effects of mycotoxins or inhibiting the growth of fungi and mycotoxin production, is deeply investigated in the available literature and some effective measures for safe utilization of mycotoxin contaminated feed/food are proposed. The biological methods of decontamination, degradation or biotransformation of mycotoxins are deeply analyzed and discussed.

Меtformin-associated maternal and neonatal outcomes in women with gestational diabetes - a retrospective cohort study.

Objectives: To assess the maternal and neonatal outcomes in women with GDM treated with metformin, medical nutrition therapy (MNT) or insulin.

Material And Methods: The current retrospective cohort study includes data from 233 women diagnosed with GDM who gave birth between January 2017 and January 2019 at an obstetrics and gynecology hospital in Sofia, Bulgaria. Patients were assigned to three groups, according to the treatment approach - metformin group (n = 70), insulin group (n = 40), and MNT group (n = 123).

Foodborne Diseases Due to Underestimated Hazard of Joint Mycotoxin Exposure at Low Levels and Possible Risk Assessment.

The subject of this review paper is to evaluate the underestimated hazard of multiple mycotoxin exposure of animals/humans for the appearance of foodborne ailments and diseases. The significance of joint mycotoxin interaction in the development of foodborne diseases is discussed, and appropriate conclusions are made. The importance of low feed/food levels of some target mycotoxins co-contaminations in food and feedstuffs for induction of target foodborne mycotoxicoses is also studied in the available literature.

Economic Burden of Cervical Cancer in Bulgaria.

Bulgaria is among the European Union (EU) countries with the highest burden of cervical cancers and life expectancy below the EU average. The majority of cervical cancer cases (more than 95%) are caused by the human papillomavirus (HPV). The aim of this retrospective, cost of illness study is to identify direct healthcare costs of cervical cancer in Bulgaria from the payer perspective and to calculate indirect costs and the associated years of life lost.

New Evidences about the Carcinogenic Effects of Ochratoxin A and Possible Prevention by Target Feed Additives.

A review of the carcinogenic effects of ochratoxin A (OTA) on various tissues and internal organs in laboratory and farm animals is made. Suggestions are made regarding how to recognize and differentiate the common spontaneous neoplastic changes characteristic for advanced age and the characteristic neoplasia in different tissues and organs in laboratory animals/poultry exposed to OTA. The synergistic effects of OTA together with its natural combination of penicillic acid are also investigated regarding possible carcinogenic effects.

Studies on teratogenic effect of ochratoxin A given via mouldy diet in mice in various sensitive periods of the pregnancy and the putative protection of phenylalanine.

Embryotoxic and teratogenic effects were found in OTA-treated pregnant Swiss albino mice, which were particularly strong at OTA contamination levels of 20 ppm (corresponding to 2.8 mg OTA/kg bw per day), when fed between the day 7 and day 12 of the pregnancy. Slighter embryotoxic and teratogenic effects were found when OTA was given up to day 7 or after day 12 of mice pregnancy.

Benefits of using a microencapsulated vitamin D delivery system in women with polycystic ovary syndrome.

Objective: To compare and assess the efficacy of two vitamin D delivery systems (oil-based and microencapsulated) on 25-hydroxy-vitamin D (25(OH)D) levels, body mass index (BMI) and insulin resistance (IR) in women with established polycystic ovary syndrome (PCOS) and vitamin D deficiency.

Materials And Methods: A monocentric, retrospective study was conducted, using the data of 70 female patients, who visited the endocrinology department of the "Dr. Shterev" Hospital, Sofia, Bulgaria between May 2020 and September 2020.

Molecular networking-assisted flavonoid profile of extract in relation to its protective effects on carbon tetrachloride-induced hepatorenal damage in rats.

The aim of the study was to provide an in-depth characterization of the methanol-aqueous extract from the aerial parts of Pall. Ex Adams (Caryophyllaceae) (EGG) and to assess its protective potential on carbon tetrachloride (CCl)-induced liver and kidney damage in male Wistar rats. Twenty-two flavonoid , - and --glycosides in EGG were annotated by mass spectrometry--based molecular networking; nine of them are reported in this species for the first time.

Study of clinical experience with different approaches to controlled ovarian hyperstimulation: a focus on safety and efficacy.

Objectives: Current retrospective cohort study analyses clinical database records of 4792 assisted reproduction procedures to assess the significance of target effectiveness endpoints from a safety perspective.

Methods: Stimulation protocols with urinary, recombinant or combination of both types gonadotrophin preparations are compared according to the following primary endpoints: incidence of ovarian hyperstimulation syndrome (OHSS), cycle cancellation, follicle count, induced estradiol values, clinical pregnancy achieved and cycles reached embryo transfer/freezing. We have investigated the incidence of cases evaluated as 'risky for OHSS' by secondary efficacy endpoints (exogenous gonadotrophin exposure, luteinising hormone and progesterone values, oocyte yield, eggs with normal maturation).

Follow up long term preliminary studies on carcinogenic and toxic effects of ochratoxin A in rats and the putative protection of phenylalanine.

Carcinogenic effects of ochratoxin A (OTA) on liver, kidneys, intestine, lung and eyes of Wistar rats exposed to 10 ppm or 5 ppm OTA in the diet and additionally supplemented or not with phenylalanine (PHE) were examined during 24-months experimental period. OTA was seen to provoke strong degenerative changes and slight pericapillary oedema in most internal organs, e.g.

Long term preliminary studies on toxic and carcinogenic effect of individual or simultaneous exposure to ochratoxin A and penicillic acid in mice.

Carcinogenic effects of ochratoxin A (OTA) on liver, kidneys, intestine, muscles and subcutaneous tissue of BALB/c albino mice divided in three experimental and one control groups (30 mice in each group - 15 males and 15 females) and exposed to 10 ppm OTA and/or 50-60 ppm penicillic acid (PA) in the diet were seen. A total 22 neoplasias were found to be induced in the mice during 20 months' experimental period. Among them 14 were malignant and 8 benign.

U-PASS: unified power analysis and forensics for qualitative traits in genetic association studies.

Summary: Despite the availability of existing calculators for statistical power analysis in genetic association studies, there has not been a model-invariant and test-independent tool that allows for both planning of prospective studies and systematic review of reported findings. In this work, we develop a web-based application U-PASS (Unified Power analysis of ASsociation Studies), implementing a unified framework for the analysis of common association tests for binary qualitative traits. The application quantifies the shared asymptotic power limits of the common association tests, and visualizes the fundamental statistical trade-off between risk allele frequency and odds ratio.

Western Medicine Versus Eastern Medicine: Do Both Have a Common Root, Scientific Background, and Worldwide Recognition?

This review is designed to initiate a discussion we believe is necessary for the biomedical community, because of some recent evidences for existing of a new body anatomical system, or the primo vascular system (PVS), which could be the missing link in the scientific explanation of the unknown mechanism of action of acupuncture. Some important questions for the medical society, (eg, "What is the main source of the mistrust of Western medicine toward traditional Oriental medicine and could it be overcome?" or "Is the PVS a real one and what is its distribution, formation, and function?" or "Are there scientific proofs for intimate relationships of the PVS with meridian system and whether the PVS would be the physical basis of meridians?") are deeply studied and appropriately answered. Various pieces of knowledge are now combined to achieve a better understanding and to provide an acceptable explanation about the functions of such new system and to explain the functional path used by traditional Eastern medicine to cure diseases.

Balkan Endemic Nephropathy - Still continuing enigma, risk assessment and underestimated hazard of joint mycotoxin exposure of animals or humans.

The spreading of mycotoxic nephropathy in animals/humans was studied. The possible etiological causes provoking this nephropathy were carefully reviewed and analyzed. The natural content of the most frequent nephrotoxic mycotoxins in target feedstuffs/foods were investigated, in addition to their significance for development of renal damages in endemic areas.

Feed exposure to FB1 can aggravate pneumonic damages in pigs provoked by P. multocida.

The possible interaction between Pasteurella multocida and the mycotoxin fumonisin B1 (FB1), recognised as one of the most often food/feed contaminant, was studied with the aim to evaluate whether and how FB1 can influence and/or complicate the development and severity of various pathological damages provoked by Pasteurella multocida in some internal organs of pigs. Heavier lung pathology was seen in pigs experimentally infected with Pasteurella multocida, when the same were exposed to 20ppm dietary levels of fumonisin B1 (FB1) as was assessed by gross pathology, pathomorphological examinations, clinical biochemistry and some immunological investigations. The most typical damages in FB1 treated pigs were the strong oedema in the lung and the slight oedema in the other internal organs and mild degenerative changes in the kidneys, whereas the typical pathomorphological findings in pigs infected with Pasteurella multocida was broncho-interstitial pneumonia.

Design and Characterization of Superpotent Bivalent Ligands Targeting Oxytocin Receptor Dimers via a Channel-Like Structure.

Dimeric/oligomeric states of G-protein coupled receptors have been difficult to target. We report here bivalent ligands consisting of two identical oxytocin-mimetics that induce a three order magnitude boost in G-protein signaling of oxytocin receptors (OTRs) in vitro and a 100- and 40-fold gain in potency in vivo in the social behavior of mice and zebrafish. Through receptor mutagenesis and interference experiments with synthetic peptides mimicking transmembrane helices (TMH), we show that such superpotent behavior follows from the binding of the bivalent ligands to dimeric receptors based on a TMH1-TMH2 interface.

Foodborne mycotoxicoses, risk assessment and underestimated hazard of masked mycotoxins and joint mycotoxin effects or interaction.

The existing hazard of joint mycotoxin exposure of animals/humans and the significance of masked mycotoxins in foods or feeds and their respective contributions to the development of some food born mycotoxicoses is briefly reviewed. The importance of joint mycotoxin interaction in the complex etiology of some foodborn mycotoxicoses is covered in depth. The toxicity of low contamination levels of some combinations of mycotoxins ingested often by farm animals was carefully studied.

Inference for dynamic and latent variable models via iterated, perturbed Bayes maps.

Iterated filtering algorithms are stochastic optimization procedures for latent variable models that recursively combine parameter perturbations with latent variable reconstruction. Previously, theoretical support for these algorithms has been based on the use of conditional moments of perturbed parameters to approximate derivatives of the log likelihood function. Here, a theoretical approach is introduced based on the convergence of an iterated Bayes map.

A comparative pathological finding in pigs exposed to fumonisin B1 and/or Mycoplasma hyopneumoniae.

A more complicated pathology was observed in female pigs infected with Mycoplasma hyopneumoniae, when the same were exposed to 20 ppm dietary levels of fumonisin B1 (FB1) starting 14 days before infection for a period of 42 days as was assessed by gross pathology and pathomorphological examinations or computed tomography, and also manifested by the strong deterioration of the pneumonic process in two pigs and the subsequent euthanizing of one pig. Typical damages in FB1-fed pigs were a strong oedema in the lung and slight oedema in the other internal organs and mild degenerative changes in the kidneys, whereas the typical pathomorphological changes in M. hyopneumoniae-infected pigs corresponded to the morphologic pattern of a catarrhal bronchointerstitial pneumonia more pronounced in the cranial and middle lobes or in the cranial third of the caudal lobe of the lung.

EXTREME VALUE THEORY WITH OPERATOR NORMING.

A new approach to extreme value theory is presented for vector data with heavy tails. The tail index is allowed to vary with direction, where the directions are not necessarily along the coordinate axes. Basic asymptotic theory is developed, using operator regular variation and extremal integrals.

Porcine/chicken or human nephropathy as the result of joint mycotoxins interaction.

A survey was made of the literature concerning the occurrence and incidence of mycotoxic nephropathy in pigs and chicks in different countries. Various etiological factors contributing to the development of the disease were considered. The main nephrotoxic fungi as well as the specific conditions for their growth and toxins production were briefly described.

Food safety and increasing hazard of mycotoxin occurrence in foods and feeds.

The possible hazard of mycotoxin occurrence in foods and feeds and some food-borne mycotoxicoses is reviewed. Management of the risk of mycotoxin contamination using some useful preventive measures against mycotoxin contamination of foods/feeds during pre- and post-harvesting periods is considered. The physical and chemical methods of mycotoxin decontamination of foods/feeds are briefly described.

Use of computed tomography and histopathologic review for lung lesions produced by the interaction between Mycoplasma hyopneumoniae and fumonisin mycotoxins in pigs.

Mycoplasma hyopneumoniae has a primary role in the porcine respiratory disease complex (PRDC). The objective of this study was to determine whether fumonisin mycotoxins influence the character and/or the severity of pathological processes induced in the lungs of pigs by Mycoplasma hyopneumoniae. Four groups of pigs (n = 7/group) were used, one fed 20 ppm fumonisin B1 (FB1) from 16 days of age (group F), one only infected with M.

Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics.

We recently reviewed the status of peptide and nonpeptide agonists and antagonists for the V(1a), V(1b) and V(2) receptors for arginine vasopressin (AVP) and the oxytocin receptor for oxytocin (OT). In the present review, we update the status of peptides and nonpeptides as: (i) research tools and (ii) therapeutic agents. We also present our recent findings on the design of fluorescent ligands for V(1b) receptor localisation and for OT receptor dimerisation.