Assessing the Risk of Depression Tendency in Pregnancy and Puerperium during COVID-19 Pandemic in Poland.

The aim of the study was to assess the risk and severity of depression tendency in pregnant and postpartum women and to determine the relative risk for selected psychosocial and obstetric variables. The study included 317 women in the perinatal period. The severity of depressive disorders was assessed using standard self-report scales: EPDS (Edinburgh Postnatal Depression Scale), BDI-II (Depression Inventory-Second Edition), and HADS (Hospital Anxiety and Depression Scale). High rates of depression tendency in women in the third trimester of pregnancy were reported in 48.05% of pregnant women (≥10 EPDS scores), 49.36% (≥12 BDI II scores), and 41.55% (≥8 HADS-D scores). In contrast, in women in the first week after delivery, respectively: 33.74%; 28.83%; 22.08%. In the EPDS assessment, 11.69% of pregnant women and 17.79% of postpartum women confirmed the presence of self-injurious thoughts. A woman's diagnosis of depressive disorder before pregnancy increases the risk of postpartum depression tendency 3.35 times according to the EPDS, 3.51 times according to the BDI-II, and 4.89 times according to the HADS-D. Depressive disorders were significantly more common in pregnant women compared to women in the first week of postpartum. Systematic screening can identify risk factors for prenatal and postpartum depression.

Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells.

During initiation of antiviral and antitumor T cell-mediated immune responses, dendritic cells (DCs) cross-present exogenous antigens on major histocompatibility complex (MHC) class I molecules. Cross-presentation relies on the unusual "leakiness" of endocytic compartments in DCs, whereby internalized proteins escape into the cytosol for proteasome-mediated generation of MHC I-binding peptides. Given that type 1 conventional DCs excel at cross-presentation, we searched for cell type-specific effectors of endocytic escape. We devised an assay suitable for genetic screening and identified a pore-forming protein, perforin-2 (Mpeg1), as a dedicated effector exclusive to cross-presenting cells. Perforin-2 was recruited to antigen-containing compartments, where it underwent maturation, releasing its pore-forming domain. Mpeg1-/- mice failed to efficiently prime CD8+ T cells to cell-associated antigens, revealing an important role for perforin-2 in cytosolic entry of antigens during cross-presentation.

A histone deacetylase 3 and mitochondrial complex I axis regulates toxic formaldehyde production.

Cells produce considerable genotoxic formaldehyde from an unknown source. We carry out a genome-wide CRISPR-Cas9 genetic screen in metabolically engineered HAP1 cells that are auxotrophic for formaldehyde to find this cellular source. We identify histone deacetylase 3 (HDAC3) as a regulator of cellular formaldehyde production. HDAC3 regulation requires deacetylase activity, and a secondary genetic screen identifies several components of mitochondrial complex I as mediators of this regulation. Metabolic profiling indicates that this unexpected mitochondrial requirement for formaldehyde detoxification is separate from energy generation. HDAC3 and complex I therefore control the abundance of a ubiquitous genotoxic metabolite.

Inorganic Nanomaterials Used in Anti-Cancer Therapies:Further Developments.

In this article, we provide an overview of the progress of scientists working to improve the quality of life of cancer patients. Among the known methods, cancer treatment methods focusing on the synergistic action of nanoparticles and nanocomposites have been proposed and described. The application of composite systems will allow precise delivery of therapeutic agents to cancer cells without systemic toxicity. The nanosystems described could be used as a high-efficiency photothermal therapy system by exploiting the properties of the individual nanoparticle components, including their magnetic, photothermal, complex, and bioactive properties. By combining the advantages of the individual components, it is possible to obtain a product that would be effective in cancer treatment. The use of nanomaterials to produce both drug carriers and those active substances with a direct anti-cancer effect has been extensively discussed. In this section, attention is paid to metallic nanoparticles, metal oxides, magnetic nanoparticles, and others. The use of complex compounds in biomedicine is also described. A group of compounds showing significant potential in anti-cancer therapies are natural compounds, which have also been discussed.

Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives.

Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status of cancer cells. Thus, these compounds might serve as potential alternatives in the oxidative therapy of GBM. The increased basal levels of reactive oxygen species (ROS) in GBM support the survival of cancer cells and cause drug resistance. The simplest approach to induce cell death is to achieve the redox threshold and circumvent the antioxidant defense mechanisms. Consequently, cells become more sensitive to oxidative stress (OS) caused by exogenous agents. Here, we investigated the effect of KR and its derivatives on the redox status of T98G cells in 2D and 3D cell culture. The use of spheroids of T98G cells enabled the selection of one derivative-7-deazaKR-with comparable antitumor activity to KR. Both compounds induced ROS generation and genotoxic OS, resulting in lipid peroxidation and leading to apoptosis. Taken together, these results demonstrated that KR and 7-deazaKR modulate the cellular redox environment of T98G cells, and vulnerability of these cells is dependent on their antioxidant capacity.

Nutrition quality of pregnant women based on body mass index and the content of selected nutrients and energy in the daily diet.

OBJECTIVES: BMI of pregnant women is influenced by the percentage of energy and the content of individual nutrients in the daily diet. The aim of the study was to evaluate nutrition quality based on BMI values of women with physiological course of pregnancy and to determine correlations between BMI and the content of selected nutrients and energy in the daily diet. MATERIAL AND METHODS: The study was carried out among healthy women between the first and fourth day after childbirth. It was conducted using a standardized questionnaire of the National Health Institute: DHQ II. In total, 103 women met the inclusion criteria. The analyses were performed with the use of a data analysis software system called Statistica 10.0. RESULTS: The mean BMI before pregnancy was 22.30 ± 3.19 kg/m². The mean BMI before delivery was 27.87 ± 3.9 kg/m². The analysis of selected nutrient intake in relation to the nutritional status based on BMI before pregnancy showed no statistically significant differences. It was found that women with normal BMI (18.5-24.9 kg/m²) consumed foods of lower energy value than those with BMI over 25 kg/m². These differences were statistically significant for daily energy intake and for the mean content of carbohydrates in the daily diet. Intake of selected nutrients was correlated in a statistically significant way with the nutritional status during pregnancy based on pre-partum BMI values. The higher the percentage of energy in the daily diet, the higher the pre-partum BMI values. Similar correlations were found for total fats, carbohydrates, protein, saturated fatty acids, mono- and polyunsaturated fatty acids, calcium, magnesium, vitamin D, water contained in foods, fluids and total sugars. CONCLUSIONS: Dietary energy and carbohydrate content has a significant impact on BMI of pregnant women. During pregnancy, BMI increases with an increase in saturated fatty acid consumption. Intake of selected nutrients was correlated in a statistically significant way with the nutritional status during pregnancy based on BMI values.

To Kill But Not Be Killed: Controlling the Activity of Mammalian Pore-Forming Proteins.

Pore-forming proteins (PFPs) are present in all domains of life, and play an important role in host-pathogen warfare and in the elimination of cancers. They can be employed to deliver specific effectors across membranes, to disrupt membrane integrity interfering with cell homeostasis, and to lyse membranes either destroying intracellular organelles or entire cells. Considering the destructive potential of PFPs, it is perhaps not surprising that mechanisms controlling their activity are remarkably complex, especially in multicellular organisms. Mammalian PFPs discovered to date include the complement membrane attack complex (MAC), perforins, as well as gasdermins. While the primary function of perforin-1 and gasdermins is to eliminate infected or cancerous host cells, perforin-2 and MAC can target pathogens directly. Yet, all mammalian PFPs are in principle capable of generating pores in membranes of healthy host cells which-if uncontrolled-could have dire, and potentially lethal consequences. In this review, we will highlight the strategies employed to protect the host from destruction by endogenous PFPs, while enabling timely and efficient elimination of target cells.

Dihydroxyacetone phosphate signals glucose availability to mTORC1.

The mechanistic target of rapamycin complex 1 (mTORC1) kinase regulates cell growth by setting the balance between anabolic and catabolic processes. To be active, mTORC1 requires the environmental presence of amino acids and glucose. While a mechanistic understanding of amino acid sensing by mTORC1 is emerging, how glucose activates mTORC1 remains mysterious. Here, we used metabolically engineered human cells lacking the canonical energy sensor AMP-activated protein kinase to identify glucose-derived metabolites required to activate mTORC1 independent of energetic stress. We show that mTORC1 senses a metabolite downstream of the aldolase and upstream of the GAPDH-catalysed steps of glycolysis and pinpoint dihydroxyacetone phosphate (DHAP) as the key molecule. In cells expressing a triose kinase, the synthesis of DHAP from DHA is sufficient to activate mTORC1 even in the absence of glucose. DHAP is a precursor for lipid synthesis, a process under the control of mTORC1, which provides a potential rationale for the sensing of DHAP by mTORC1.

Small Molecule Enhancers of Endosome-to-Cytosol Import Augment Anti-tumor Immunity.

Cross-presentation of antigens by dendritic cells (DCs) is critical for initiation of anti-tumor immune responses. Yet, key steps involved in trafficking of antigens taken up by DCs remain incompletely understood. Here, we screen 700 US Food and Drug Administration (FDA)-approved drugs and identify 37 enhancers of antigen import from endolysosomes into the cytosol. To reveal their mechanism of action, we generate proteomic organellar maps of control and drug-treated DCs (focusing on two compounds, prazosin and tamoxifen). By combining organellar mapping, quantitative proteomics, and microscopy, we conclude that import enhancers undergo lysosomal trapping leading to membrane permeation and antigen release. Enhancing antigen import facilitates cross-presentation of soluble and cell-associated antigens. Systemic administration of prazosin leads to reduced growth of MC38 tumors and to a synergistic effect with checkpoint immunotherapy in a melanoma model. Thus, inefficient antigen import into the cytosol limits antigen cross-presentation, restraining the potency of anti-tumor immune responses and efficacy of checkpoint blockers.

SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway.

mTOR complex 1 (mTORC1) regulates cell growth and metabolism in response to multiple environmental cues. Nutrients signal via the Rag guanosine triphosphatases (GTPases) to promote the localization of mTORC1 to the lysosomal surface, its site of activation. We identified SAMTOR, a previously uncharacterized protein, which inhibits mTORC1 signaling by interacting with GATOR1, the GTPase activating protein (GAP) for RagA/B. We found that the methyl donor S-adenosylmethionine (SAM) disrupts the SAMTOR-GATOR1 complex by binding directly to SAMTOR with a dissociation constant of approximately 7 µM. In cells, methionine starvation reduces SAM levels below this dissociation constant and promotes the association of SAMTOR with GATOR1, thereby inhibiting mTORC1 signaling in a SAMTOR-dependent fashion. Methionine-induced activation of mTORC1 requires the SAM binding capacity of SAMTOR. Thus, SAMTOR is a SAM sensor that links methionine and one-carbon metabolism to mTORC1 signaling.

The preferences of parturient women and the participation of the child's father during birth.

BACKGROUND: The participation of the father in the birth manifests itself in action, that depends on the attitude towards family-assisted birth and the preferences of the parturient woman. AIM: Evaluation of expectations of parturient women in the aspect of the active participation of the father, that would enable the use of the most commonly reported preferences in the clinical praxis and the establishment of factors influencing the presented preferences. METHODS: 250 married couples who participated in natural childbirth were subjected to prospective survey. Couples after physiological delivery with the participation of father in all stages of childbirth were qualified. The surveys were conducted in the first day after the childbirth. The survey tool was an author-developed survey questionnaire in two versions: (A) for the mother and (B) for the child's father who participated in the birth. The statistical calculations were performed with use of the Statistica PL software. The frequency of occurrence of respective quality (non-measurable) features was evaluated with χ² (chi-square) nonparametric test. The level of statistical significance adopted for tests was p<0.05. RESULTS: The preferences of parturient women, regardless of their age, education, duration of marriage, number of family-assisted births and the form of preparation mostly concerned the adaptation of a supportive role by the fathers, on every stage of the birth. During the second stage of birth 74.4% of parturient women expected the father to cut the umbilical cord. After the birth the majority of mothers (76%) preferred the presence of the father in post-delivery period. CONCLUSIONS: The pre-birth education of couples of parents should include the expectations of the parturient woman, regarding the forms of father's activity during a family-assisted birth. High expectations of parturient women regarding the emotional support indicate the need for educating future fathers, as there is large demand for such element of mid-delivery care.

[Pregnancy and delivery course in overweight and obese women]. / Przebieg ciazy i porodu u ciezarnych z nadmierna masa ciala.

INTRODUCTION: Pregnancy and delivery in case of overweight women require special care. The main means of preventing obstetrical complications is promoting healthy lifestyle and pregnancy weight gain control among females planning the pregnancy as well as prenatal diagnosis and pregnancy/delivery course monitoring. OBJECTIVES: The aim of the study was to evaluate the pregnancy and delivery course in overweight and obese pregnant women. MATERIAL AND METHODS: The study was based on a retrospective analysis of medical files of 132 pregnant women delivering in Gynecology and Obstetrics Clinic in Tychy, Poland. The investigated group was divided into subgroups based on pre-pregnancy body mass index according to World Health Organization Criteria for obesity. The comparative analysis was then performed between the subgroups. RESULTS: The prevalence of bleedings in pregnancy pregnancy induced hypertension, diabetes and urinary tract infections was statistically higher in obese pregnant females. Similarly the rate of shoulder dystocia was statistically higher in the obese and overweight subgroups of women. There were no significant differences between subgroups in mean neonate body length or mean Apgar scores. However the highest neonate body weight was observer in subgroup of overweight females and those with pre-pregnancy normal BMI who gained more than 16 kilograms during pregnancy. CONCLUSIONS: 1. Excessive weight gain in pregnancy is associated with higher risk of pregnancy and delivery complications. 2. Both excessive pre-pregnancy body weight and excessive weight gain in pregnancy increase the risk of perinatal complications.

IL-18 levels in nasal lavage after inhalatory challenge test with flour in bakers diagnosed with occupational asthma.

OBJECTIVES: The authors discuss the outcomes of a study on IL-18 concentration in nasal washings after the inhalatory challenge test with flour allergens (ICHT-F) in bakers with flour-induced occupational airway allergy (OAA). METHODS: We measured IL-18 concentration using ELISA kit and assessed morphological changes in nasal lavage fluid (NLF) before, and 4 h and 24 h after ICHT-F in three groups of subjects: Group A - 9 patients with diagnosed OAA (occupational asthma and rhinitis), Group B - 10 patients with atopic asthma and rhinitis, and Group C - 9 healthy volunteers. RESULTS: In Group A, significant differences in the basophil proportion in NLF were noted only 24 h after ICHT-F. Both the basophil proportion and total eosinophil count were higher in Group A than in Group C at this time-point. Group A also showed a statistically significant increase in IL-18 levels 4 h after the challenge. A significant relationship was noted between the proportion of basophils 4 h after ICHT-F and IL-18 level at 24 h after the test. CONCLUSIONS: This is the first study demonstrating an increased expression of IL-18 in nasal washings of subjects diagnosed with OAA to flour allergens. The observed higher concentrations of IL-18 in nasal washings after ICHT as well as the increase in the proportion of basophils provide evidence for the important role of IL-18 in persistent allergic inflammation.

Risk factors associated with airway allergic diseases from exposure to laboratory animal allergens among veterinarians.

OBJECTIVES: Investigate the risk factors for the development of occupational airway allergy (OAA) from exposure to laboratory animal allergens (LAA) among Polish veterinarians. METHODS: Two hundred veterinarians responded to the questionnaire and were subjected to skin prick test (SPT) to common allergens and LAA (rat, mouse, hamster, guinea pig, rabbit). Evaluation of total serum IgE level and specific IgE against occupational allergens was performed. In addition, bronchial hyperreactivity (BHR) and peak expiratory flow rate (PEFR) were measured before and after specific challenge testing (SCT) only in the subjects with work-related symptoms suggestive of occupational asthma (OA). RESULTS: The prevalence of asthmatic and ocular symptoms was statistically more prevalent in the group of veterinarians sensitised to LAA versus non-sensitised subjects. The most frequent occupational allergens of skin and serum reactivity were LAA (44.5 and 31.5%, respectively). In 41 (20.5%) and in 22 (11%) subjects out of 200 veterinarians, serum specific IgE to natural rubber latex (NRL) allergens and disinfectants was also found. Serum sensitisation to cat allergens and daily contact with laboratory animals (LA) increased the risk for developing isolated occupational rhinitis. Furthermore, working time of more than 10 years and daily contact with LA were also significant risk factors for the development of OAA. Measuring PEFR and BHR before and after SCT is a useful method to confirm the presence of OA. CONCLUSIONS: Allergy to LAA is an important health problem among veterinary medicine practitioners in Poland.

Prevalence and host determinants of occupational bronchial asthma in animal shelter workers.

OBJECTIVE: We examined the risk factors for the development of airway allergy in animal shelter workers. METHODS: The study population comprised 88 animal shelter workers occupationally exposed to cats and dogs. They responded to a questionnaire concerning the history of exposure to animal allergens and job characteristics and were subjected to skin prick test (SPT) to common and occupational allergens (cat and dog), and determination of total serum IgE level and specific IgE. In addition, SPT with rat and mouse allergens were performed. Bronchial hyperreactivity and peak expiratory flow rate were measured at work and off work only in workers with work-related symptoms suggestive of occupational asthma (OA). RESULTS: The prevalence of OA was 9.1%. Sensitization to dog allergens was higher than to cats. The multivariate logistic regression analysis revealed a significant role of positive family history of atopy and having a dog as pet in the past for the development of occupational airway allergy (OR 5.9; 95% CI 1.76, 20.00; P = 0.003; OR 6.47; 95% CI 1.90, 22.02; P = 0.002, respectively). In the multivariate logistic regression analysis, the risk for developing OA was most clearly associated with growing up in the country (OR 7.59; 95% CI 1.25, 45.9; P = 0.025). CONCLUSIONS: Allergic disease is a serious occupational health concern for subjects who have occupational contact with cats and dogs.

Outbreak of lead poisoning in high voltage tower conservators.

OBJECTIVES: A changing character of lead exposure has been observed over many years. However, construction workers involved in the renovation of painted steel structures are still severely exposed to lead and its compounds. In 2004, we observed an outbreak of lead poisoning in high voltage tower conservators working abroad. MATERIALS AND METHODS: As many as 27 male workers with suspected lead poisoning were hospitalized in the Department of Occupational Disease, Nofer Institute of Occupational Medicine, Lódz, Poland. They were involved in removing an old lead-containing paint from high voltage towers. RESULTS: On admission to the department, 70% of treated workers showed laboratory signs of anemia in their blood count. After treatment the signs persisted in 25% of patients. Also alkaline dotting in erythrocytes was present in 13 subjects. Sub-acute lead poisoning manifested by abdominal cramps with coexisting anemia and increased lead absorption symptoms was most frequently diagnosed. CONCLUSIONS: The high lead exposure of the examined high voltage tower cleaners was due to specific working conditions. In such cases overprotection of the environment may lead to severe health effects in humans.