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Deregulation of ten-eleven Translocation protein 1 (TET1) is commonly reported to induce imbalances in gene expression and subsequently to colorectal cancer development (CRC). On the other hand, vitamin C (VitC) improves the prognosis of colorectal cancer by reprogramming the cancer epigenome and limiting chemotherapeutic drug resistance events. In this study, we aimed to characterize TET1-specific subcellular compartments and evaluate the effect of VitC on TET1 compartmentalization in colonic tumour cells. We demonstrated that TET1 is concentrated in coarse nuclear bodies (NB) and 5-hydroxymethylcytosine (5hmC) in foci in colorectal cancer cells (HCT116, Caco-2, and HT-29). To our knowledge, this is the first report of a novel intracellular localization profile of TET1 and its demethylation marker, 5hmC, in CRC cells. Interestingly, we found that TET1-NBs frequently interacted with Cajal bodies, but not with promyelocytic leukaemia (PML) bodies. In addition, we report that VitC treatment of HCT116 cells induces 5hmC foci biogenesis and triggers 5hmC marks to form active complexes with nuclear body components, including both Cajal and PML proteins. Our data highlight novel NB-concentrating TET1 in CRC cells and demonstrate that VitC modulates TET1-NBs' interactions with other nuclear structures. These findings reveal novel TET1-dependent cellular functions and potentially provide new insights for CRC management.

Colorectal cancer (CRC) is ranked the second most lethal type of tumor globally. Thus, developing novel anti-cancer therapeutics that are less aggressive and more potent is needed. Recently, natural bioactive molecules are gaining interest as complementary and supportive antineoplastic treatments due to their safety, effectiveness, and low cost. Jania rubens ( J. rubens ) is a red coral seaweed abundant in the Mediterranean and bears a significant pharmacological essence. Despite its therapeutic potential, the natural biomolecules extracted from this alga are poorly identified. In this study, the proximal analysis revealed high levels of total ash content (66%), 11.3% proteins, 14.5% carbohydrates, and only 4.5% lipids. The elemental identification showed magnesium and calcium were high among its macro minerals, (24 ± 0.5 mg/g) and (33 ± 0.5 mg/g), respectively. The Chlorophyll of J. rubens was dominated by other pigments with (0.82 ± 0.02 mg/g). A 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay identified effective antioxidant activity in various J. rubens extracts. More importantly, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tetrazolium reduction and wound healing assays indicate that organic extracts from J. rubens significantly counteract the proliferation of colon cancer cell lines (HCT-116 and HT-29) and inhibit their migratory and metastatic properties in a dose and time-dependent manner. Overall, this study provides insight into the physicochemical properties of red seaweed, J. rubens , and identifies its significant antioxidant, cytotoxic, and anti-migratory potential on two colorectal cell lines, HCT-116 and HT-29.

We have previously shown that effector memory (TEM) cells accumulate in the bone marrow (BM) and the kidney in response to l-NAME/high salt challenge. It is not well understood if measures to block the exodus of that effector memory cells prevent redistribution of these cells and protect from hypertension-induced renal damage. We hypothesized that that effector memory cells that accumulate in the bone marrow respond to repeated salt challenges and can be reactivated and circulate to the kidney. Thus, to determine if mobilization of bone marrow that effector memory cells and secondary lymphoid organs contribute to the hypertensive response to delayed salt challenges, we employed fingolimod (FTY720), an S1PR1 functional antagonist by downregulating S1PR, which inhibits the egress of that effector memory cells used effectively in the treatment of multiple sclerosis and cardiovascular diseases. We exposed wild-type mice to the l-NAME for 2 weeks, followed by a wash-out period, a high salt diet feeding for 4 weeks, a wash-out period, and then a second high salt challenge with or without fingolimod. A striking finding is that that effector memory cell egress was dramatically attenuated from the bone marrow of mice treated with fingolimod with an associated reduction of renal that effector memory cells. Mice receiving fingolimod were protected from hypertension. We found that wild-type mice that received fingolimod during the second high salt challenge had a marked decrease in the renal damage markers. CD3 + T cell infiltration was significantly attenuated in the fingolimod-treated mice. To further examine the redistribution of bone marrow that effector memory cells in response to repeated hypertensive stimuli, we harvested the bone marrow from CD45.2 mice following the repeated high salt protocol with or without fingolimod; that effector memory cells were sorted and adoptively transferred (AT) to CD45.1 naïve recipients. Adoptively transferred that effector memory cells from mice treated with fingolimod failed to home to the bone marrow and traffic to the kidney in response to a high salt diet. We conclude that memory T cell mobilization contributes to the predisposition to hypertension and end-organ damage for prolonged periods following an initial episode of hypertension. Blocking the exodus of reactivated that effector memory cells from the bone marrow protects the kidney from hypertension-induced end-organ damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Itani, Jarrah, Maaliki, Radwan, Farhat and Itani.)

Objectives: An elevated maximal amplitude (mA) value with rapid thrombelastography on admission can identify general trauma patients with an increased risk of venous thromboembolic events (VTEs). We hypothesized that (1) the risk of VTE traditionally assigned to injury lies specifically in those who sustain major orthopaedic trauma and (2) an elevated admission mA value could be used to identify patients with major orthopaedic injuries at risk for VTE during initial hospital admission., Design: Retrospective., Setting: University level 1 trauma center., Patients/participants: Consecutive trauma patients admitted to an urban level 1 trauma center between September 2009 and February 2011 who met the criteria for level 1 trauma activation and who were between 18 and 85 years of age were included in our study group. Two groups were created, one whose extremity abbreviated injury severity score was 2 or greater (ORTHO) and the other whose extremity abbreviated injury severity score was <2 (non-ORTHO)., Main Outcome Measurements: Pulmonary emboli were confirmed by computed tomography angiography, and deep vein thromboses were confirmed by venous duplex. Univariate analyses were conducted and followed by purposeful regression analysis., Results: Of note, 1818 patients met the inclusion criteria (310 ORTHO and 1508 non-ORTHO). Despite more hypocoagulable r-TEG values on arrival (alpha angle 71 vs. 73 and mA 62 vs. 64, both P < 0.05), ORTHO patients had higher rates of VTE (6.5% vs. 2.7%, P < 0.001). Stepwise regression generated 4 values to predict development of VTE (age, male gender, white race, and ORTHO). After controlling for these variables, admission mA values ≥65 (odds ratio 3.66) and ≥72 (odds ratio 6.70) were independent predictors of VTEs during hospitalization., Conclusions: Admission rapid thrombelastography mA values can identify patients with major orthopaedic trauma injuries who present with an increased risk of in-hospital deep vein thromboses and pulmonary embolism with a 3.6-fold and 6.7-fold increased risk for mA values ≥65 and ≥72, respectively., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background: The aim of the study was to define the frequency of menstrual disorders and identify risk factors, especially those associated with the work environment., Materials and Methods: The study group was composed of 142 women, aged 22-45 years. Some of them were employed in a cosmetics manufacture plant and a bank, others were hospital and ambulatory nurses and auxiliary personnel., Results and Conclusions: The study revealed irregular cycles in one third and prolonged bleeding in one fourth of the women. Long cycles were observed in one fifth of the women and short cycles were noted in every tenth women. It was found that occasional or frequent contact with ethylene oxide increased the risk of irregular cycles and oligomenorrhea, whereas work around X-ray apparatus was responsible for the risk of long cycles and heavy bleeding. Long rest pauses during work (in this study correlated with work load) were regarded as a factor inducing the risk of oligomenorrhea and prolonged bleeding. A randomly sampled group of 33 women measured morning temperature during two consecutive cycles. Of this number, 15 women (45.5%) showed ovulation in both cycles, 11 (33.3%) in one cycle only, and 7 both anovulatory cycles. The risk of ovulation disorders was enhanced by a two-shift work system (mostly night shift) and strong job stress. Energy expenditure for leisure time activity > 1000 kcal/week and smoking also contributed to an enhanced risk. In summing up, it should be stressed that because of varied frequency of irregular cycles determined by the intensity of environmental factors, occupational medicine physicians should gather data on the occurrence of such disorders and undertake relevant preventive measures.

Background: The aim of the study was to define the incidence of prematurity and small-for-gestational age (SGA) infants in occupationally involved pregnant women, and to find out how far working conditions departing from binding regulations contribute to the risk of the development of these pathologies., Materials and Methods: The study was carried out on a representative sample of 3050 women employed for longer than one week during pregnancy in the Łódź district. An interview conducted with the subjects few days after delivery was the source of information about working conditions. The obtained information was compared with the real situation in about 10% of randomly selected workposts. A high level of consistence was observed., Results: The study revealed that almost 60% of women work in conditions, which do not comply with the Labor Code provisions setting working conditions permissible for pregnant women. In the study group, 4.68% of prematurity and 6.15% of SGA were recorded. A 66% excess in the risk of delivering SGA infants in case of at least one factor not complying with regulations was revealed. The excess was growing with the increased number of departures from regulations and continuation of employment during pregnancy. It was estimated that the number of SGA cases would decrease by 28% if the working conditions would have met the requirements. A prolonged time of work, local vibration for > 4h/shift, forced work pace, excessive effort and forced body position during the work performance contributed mostly to the risk of pathology. Interestingly, the risk of premature delivery was lower by about 40% in women working in unsatisfactory conditions, which is attributed to termination of work immediately after the occurrence of pregnancy-threatening symptoms. Only those women whose pregnancy was not threatened with pathology could continue their work., Conclusions: The study revealed a quite large number of workplaces not complying with regulations on working conditions permissible for pregnant women. Therefore, studies in this area should be continued by physicians attending pregnant women, under programs aimed at preventing prematurity, and they should be expanded to include the detection of SGA during gestation and the implementation of relevant prophylactics.

To define the range and kind of discrepancies between regulations and actual state of working conditions and occupations performed by women during pregnancy, a survey was carried out in the population of 2649 women, a representative group of occupationally involved pregnant women in the region of Łódź. The questionnaire analysis provided information on the kind and arduousness of work performed, working hours and conditions in the work environment. Having verified the data obtained from 10% of women, a very high consistency between working conditions described by respondents and evaluated by experts was noted. Its was found that almost 60% of women under study indicated that their working conditions depart from those defined as admissible for women during pregnancy. Of the women who worked only during the first month of pregnancy, 75% of them were employed at workposts, which did not meet the requirements, and nearly half of women who worked during the whole period of pregnancy were employed in inappropriate conditions. The noxiousness most frequently reported by respondents applied to body posture: bending and position with rotated spine (about 40%). This was followed by lifting and carrying various objects (about 30%), prolonged working hours (about 20%), shift work, including night shifts (about 12%), work at conveyor belt and forced work pace (about 20%). Noise that makes it difficult to communicate, local vibration and work with computers over 4 hours daily was reported by 30% and 15% of respondents, respectively. The most common solution to limit the potential effect of hazardous and noxious working conditions on pregnant women was to remove them from work by issuing a sick leave certificates, while the modification of working conditions or shifting them to another post applied only to 14% of women. The results of the study showed that working conditions of pregnant women differed from those described by the State Labor Inspectorate. The discrepancy can be explained by different method of data collection.

Background: The aim of the study was to define associations between intensity of perimenstrual complaints, the type of job performed and working conditions, taking also account of non-occupational factors. The study preceding the development of a preventive program was carried out in a group of women employed in work settings different in the character and burden of adverse agents., Materials and Methods: The group was composed of 142 women, aged 21-45 years, employed in a cosmetics manufacture plant (27%) and a bank (27%), as well as of hospital and ambulatory nurses and auxiliary personnel (50%). A questionnaire on premenstrual and menstrual complaints, working conditions, characteristics of the women and their household duties load was the main tool of the study., Results: The study revealed that about 80% of women experienced premenstrual and about 75% menstrual symptoms, which were strongly intensified in 40% of women. After applying logistic regression, it was found that physical workload and occupational stress were the major occupational risk factors, whereas chronic diseases, age, household duties load and alcohol consumption were the major non-occupational risk factors., Conclusions: The evidenced relationship between complaints and adverse agents typical of the job performed should prompt occupational medicine physicians to more comprehensive analysis of individual jobs in view of reducing occupational load.

In Poland, the assessment of work ability has thus far been almost entirely objective, which means that it was based on the evaluation of the individual's health state. That is why a subjective method of work ability assessment with work ability index (WAI), developed by the Occupational Health Institute in Helsinki, was used in our present study. This method allows to indicate other possible factors which modify work ability. The study covered 189 men employed in five metallurgical plants, located in the region of Lódź. In the study population, WAI and work load on the basis of the expenditure of energy were measured, the health condition was evaluated, and information on life styles and non-occupational responsibilities was gathered. It was found that WAI values were inversely proportional to age and work load. They were also modified by individual characteristics, such as life style, body mass, and activities at leisure. It was found that the correlation between the general index of work ability and the objective health indicators was low with the concomitant considerably higher correlation with the values of the components which reflect subjective work abilities. In view of the results obtained, WAI can be recommended as a tool for assessing work ability. Due to this method it is possible to present conclusively all elements of individual characteristics and to identify at the same time links with working conditions.

The body mass is one of the major indicators which determine the clinical condition of newborns, influence the rate of neonatal mortality and further development of newborns. In order to prevent malformations it is necessary to identify factors which impair the fetus development and cause fetal hypotrophy. The main objective of the study was to find out whether mothers' occupational work affected the body mass of infants born at term. The study covered a group of 1015 women randomly sampled among those who had delivered their babies in the Polish Mother Memorial Hospital in Lódź, during the years 1992-94. In this group the percentage of working women accounted for 69%. The comparison of the body mass in infants born to women employed and not employed during pregnancy did not indicate differences. However, it was found that male infants born to employed mothers showed a lower body mass than those born to not employed mothers. The effect of some factors modifying infants' body mass was different in the case of not employed women than in those employed. In the group of not employed women a significantly lower body mass in infants was observed in the following subgroups: mothers under 24 years of age, spontaneous abortion of one of previous pregnancies, consumption of large quantity of caffeine (equivalent of > two cups of coffee), and poor economic status. Smoking during pregnancy decreased the body mass of infants in both groups of women. In the group of working women, chronic diseases before pregnancy and diseases involving fever during pregnancy proved to be factors affecting the body mass of infants. The indicators of perinatal medical care (the beginning of medical care and the number of visits during pregnancy) in working women were better than in those not working. None of factors characterizing occupational work affected significantly the body mass of infants. Slightly lower infants' body mass was observed only in those born to mothers working overtime (> 9 hrs daily), involved in hard physical work or working in the environment with harmful chemical and physical factors. According to the data obtained, a negative effect of occupational work on the fetus development should not be overestimated. Nevertheless, the performance of occupational work may aggravate a negative effect of woman's bad health condition on the fetus development.

The authors present a review of the literature on adverse effects of chemical and physical factors in the work environment on the course and outcome of pregnancy together with the results of their own study. The objective of the study was to identify the magnitude and frequency of exposures to chemical and physical factors at workposts where pregnant women were employed and to asses to what extent the existing exposure increased the risk for complications in pregnancy outcome The study involved the collection of information on factors with potential adverse effect on the course and outcome of pregnancy in employed women who were hospitalised in the Polish Mother Memorial Hospital in Lódź during the years 1992-94. The study was carried out in the group of 526 women with abnormal pregnancy outcome (N), including preterm birth (PB)--256; low birth weight < 2500 g (LBW)--232; small for gestational age (SGA)--196; asphyxia (APG)--116; and congenital malformations (M)--71. The control group (C) was composed of 683 women. As the reports on the work environment indicated working conditions in the group of women with abnormal pregnancy outcome were worse than in the control group; the presence of potentially harmful factors in the work environment were reported 57% of women in group N and 51.2% of women in group C. The increase in the risk of abnormal pregnancy outcome was relatively law (OR = 1.26). Taken into account the duration of exposure to these factors (period of employment under conditions of exposure to physical and/or chemical factors) it was revealed that pregnancy is at risk if women continue to work under such work conditions by the end of the second trimester. In this group of women odd ratio for abnormal pregnancy outcome accounted for 1.80 and it was statistically significant. The employment in the period preceding pregnancy and during the first trimester enhanced the risk insignificantly. A similar situation was observed if the risk of abnormal pregnancy outcome was assessed separately for exposure to chemical factors and to physical factors. A conclusion of great practical importance can be then drawn: expecting mothers should be prevented from working under harmful work conditions after the first trimester of gestation. Therefore, doctors attending occupationally working pregnant women should be obliged to make very careful inquiries about their working conditions. Logistic regression analysis helped to reveal and adverse effect of physical factors only in regard to newborns' body weight, but if failed to show negative effect of chemical factors on pregnancy outcome. On the other hand, the analysis highlighted a significant influence on certain social situations, lifestyles and mothers' health status on pregnancy outcome; a positive effect of higher education in the case of preterm birth and asphyxia; and a negative effect of mother's single status, smoking during pregnancy and the poor health condition during pregnancy on the incidence of congenital malformations.

The aim of the study was to determine the degree to which the heart rate during and after work of variable physical and mental load was affected by the mental workload of moderate intensity. The subjects were 150 women aged 17-57. 24-hour recordings of their heart rates during work, leisure and sleep were taken using the Medilog recording-analysing system. Mental workload was determined in two ways: by the AET method, which enabled objective evaluation of the load, and by a method which involved subjective evaluation of work requirements and the ability to cope with them. Using the multiple regression analysis, the degree to which concurrent elements of mental and physical workload an serve as predictors of heart rate during work, leisure and sleep. The results show that physical workload is the more essential factor affecting the reaction of the circulatory system under the circumstances of concurrent mental and physical workload. By extending the measurements to involve off-duty hours, it was possible to determine that the consequences of mental workload manifested also after the work. The prolonged effect of mental workload on the heart rate was evident only when the subjective method of workload estimation was used. This points to the individual character of mental workload. The findings indicate on one hand that the share of mental workload should not be neglected during evaluation of the effects of occupational workload on the physiological reactions and, on the other, that the heart rate measurement is a useful tool for indicating essential elements of workload.

The aim of our study was to evaluate the reaction of the circulatory system on work with various levels of physical and mental load. The examinations were carried out at a department store in two groups of women: 20 cashiers (mental work) and 53 saleswomen (physical work). There were no statistically significant differences in age, duration of employment or physical fitness between those groups. Work at this department store was performed on a two-shift system with irregular rotations. The psychic load was evaluated as a relation between subjective estimation of work demands and the ability to cope with them. Physical effort was measured as an energy expenditure during work. Cardiovascular reaction was expressed by heart rate during work, leisure time and sleep estimated according to the 24-hour Holter monitoring method. No statistically significant differences in heart rate were found to exist between cashiers and saleswomen. This, taking into account the much higher energy expenditure in saleswomen, suggests that mental effort is likely to affect heart rate. In fact, mean values of subjective assessment of work demands in cashiers were much higher (5.1) than in saleswomen (4.4), unlike the evaluation of the ability to cope with them, which points to the occurrence of a significant psychic load in the work of cashiers. A lower difference between maximum and minimum frequencies of heart rate in cashiers in comparison with saleswomen confirmed this observation, although it might have resulted from different levels of physical activity during work.(ABSTRACT TRUNCATED AT 250 WORDS)

The study has been aimed at showing the advantages of using the AET ergonomic job description for estimation of physical workload, as compared to the traditional methods in which the estimates are made on the basis of the value of energy expenditure, static load and motion monotypicity. From tests on employees at 28 workposts it has been found that by analysing 17 factors involved in the overall estimate of physical workload according to AET, it is possible to characterize the work more precisely. The results of the tests indicate that AET estimates of heavy dynamic work are strongly correlated with the size of energy expenditure, whereas the estimation of body position--with the estimate of static load and the frequency estimate--with the estimate of motion monotypicity. New possibilities, with regard to the traditional method of physical workload estimation, are opened up by the AET method in relation to light dynamic work and static effort. The physical workload rate, calculated according to the AET method as the total of 17 elements estimated, does not differentiate the values of the workloads at individual workposts and, therefore, requires physiological verification.

In order to evaluate the effect of particular elements of physical workload on the heart rate in a group of 148 women working at 18 work-posts whose jobs were characterized by different physical workload, 24-hour cardiograms were made using Holter's method and applying the Medilog 3000 (Oxford). It was observed that heart rate heart rate during work was higher in women who performed jobs demanding dynamic physical effort, and lower in those subjects who performed static work. Heart rate during work was positively correlated with the dynamic effort intensity and negatively--with the intensity of light dynamic work and static workload, which means that particular elements of physical workload are of different physiological importance. Therefore, the synthetic indicator of physical workload cannot be treated as a sum of the intensity of particular elements. Consequences of physical workload lasted during daytime. During sleep and leisure hours the effect of physical workload intensity upon the cardiac contraction frequency is not significant.

The load of the circulatory system during work is usually evaluated basing on the heart beats above the heart rate at rest (i.e. the difference between the heart rate during work and at rest). To differentiate this evaluation according to the subjects' age, the percentage of heart rate reserve (the difference between the maximum heart rate and that at rest), constituted by the heart beats above the heart rate during work and at rest). To differentiate this evaluation according to the subjects' age, the percentage of heart rate reserve (the difference between the kers as well as at the model exercise on cycle ergometer in the group of students and female whitecollar workers has demonstrated that the heart rate before work is often higher than at breaks during the working day, whereas the heart rate during work depends on the output level when work results in a slight tachycardia. It was also found that incusion of the maximum heart rate results in much greater changes in evaluating individual groups--when it is calculated what percentage of this value constitutes heart rate at work, then when calculating the heart rate reserve percentage constituted by the difference between the maximum heart rate and that at rest. Therefore the calculation of the percentage of the maximum heart rate is promoted for evaluating the load of the circulatory system during work.

A method of calculating the synthetic index of effort capability, based on results of submaximal effort test, has been presented. Examinations of people working at 4 workstations demonstrated that the reduced effort capability after work is proportional to work energetic expenditure. The usefulness of work fatigue analysis has been indicated, as its magnitude, when accompanied by evaluation of effort capability changes, points to static load as an additional disadvantageous factor.

Pure trichloroethylene (tri), stabilized by an amine base, was administered by inhalation at 0, 100, and 500 ppm for 6 h/day, 5 days/week, for 18 months to mice, rats and Syrian hamsters of both sexes. No significant increase in tumor formation was observed in any species or dosing group, except in malignant lymphomas, which were increased in female mice in the following incidence rates: 9/29 (controls), 17/30 (100 ppm), and 18/28 (500 ppm). Whether or not this high occurrence of lymphomas, which is peculiar to this strain of mice (NMRI) has any relationship to tri-exposure, cannot be decided upon by the present experiment. It is concluded that from these findings no indication for a carcinogenic potential of pure trichloroethylene can be deduced.

This paper is aimed at the determination of the relationship between the heart rate and results of subjective rating of the workload in women working in the forming and sewing workrooms of the hosiery plant. The work in these workrooms differed in respect of organization, degree of motorial activity, type of activities performed, and working conditions. The subjective rating involved 22 symptoms evaluated three times during a working day, by a 5 -- degree scale. During the same periods heart rate was determined telemetrically. In forming women, heart rate was higher by approx. 11%, and average rating by around 7%, as compared to sewing women. In both groups a positive correlation was found between the heart rate and symptoms typical of general fatigue and working conditions. On the other hand, the correlation between symptoms of monotony sensation and rating of hands efficiency was negative. The correlation between the heart rate and average rating was positive in forming women and negative in sewing women, which indicates that the similar total rating of the workload resulted form different causes (general fatigue and working conditions in forming women and monotony sensation and a great number of hands movements in sewing women.)