Ethynylestradiol feminizes gene expression partly in testis developing as ovotestis and disrupts asymmetric müllerian duct development by eliminating asymmetric gene expression in japanese quail embryos.

In avian embryos, xenoestrogens induce abnormalities in reproductive organs, particularly the testes and Müllerian ducts (MDs). However, the molecular mechanisms remain poorly understood. We investigated the effects of ethynylestradiol (EE2) exposure on gene expression associated with reproductive organ development in Japanese quail embryos. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis revealed that the left testis containing ovary-like tissues following EE2 exposure highly expressed the genes for steroidogenic enzymes (P450scc, P45017α, lyase, and 3ß-HSD) and estrogen receptor-ß, compared to the right testis. No asymmetry was found in these gene expression without EE2. EE2 induced hypertrophy in female MDs and suppressed atrophy in male MDs on both sides. RNA sequencing analysis of female MDs showed 1,366 differentially expressed genes between developing left MD and atrophied right MD in the absence of EE2, and these genes were enriched in Gene Ontology terms related to organogenesis, including cell proliferation, migration and differentiation, and angiogenesis. However, EE2 reduced asymmetrically expressed genes to 21. RT-qPCR analysis indicated that genes promoting cell cycle progression and oncogenesis were more highly expressed in the left MD than in the right MD, but EE2 eliminated such asymmetric gene expression by increasing levels on the right side. EE2-exposed males showed overexpression of these genes in both MDs. This study reveals part of the molecular basis of xenoestrogen-induced abnormalities in avian reproductive organs, where EE2 may partly feminize gene expression in the left testis, developing as the ovotestis, and induce bilateral MD malformation by canceling asymmetric gene expression underlying MD development.

In ovo o,p'-DDT exposure induces malformation of reproductive organs and alters the expression of genes controlling sexual differentiation in Japanese quail embryo.

In ovo exposure to o,p'-dichloro-diphenyl-trichloroethane (o,p'-DDT) impairs reproduction by inducing malformation of the reproductive organs in birds, although the mechanism remains unclear. Here, we examined the effects of o,p'-DDT on the development of the reproductive organs, the expression of genes controlling sexual differentiation, and the plasma concentrations of testosterone and estradiol in Japanese quail embryos. o,p'-DDT-containing sesame oil was injected into the yolk sac on Embryonic Day (E) 3 at a dose of 500, 2,000, or 8,000 µg per egg. On E15, the reproductive organs were observed; the gonads and Müllerian ducts (MDs) were sampled to measure the mRNA of steroidogenic enzymes, sex steroid receptors, anti-Müllerian hormone (AMH), and AMH receptor 2 (AMHR2); blood samples were collected to assay plasma testosterone and estradiol levels; and the gonads were used for histological analysis. o,p'-DDT dose-dependently increased the prevalence of hypertrophic MDs in females and residual MDs in males. In female MDs, o,p'-DDT dose-dependently decreased estrogen receptor (ER) α, ERß, and AMHR2 mRNA expression. o,p'-DDT dose-dependently induced left-biased asymmetry of testis size, and ovary-like tissue was found in the left testis after exposure to 8,000 µg per egg o,p'-DDT, although asymmetric gene expression did not occur. o,p'-DDT did not affect ovarian tissue but did decrease 17α-hydroxylase/C17-20 lyase mRNA expression and dose-dependently increased ERß mRNA expression. o,p'-DDT decreased plasma testosterone concentrations in females. These findings suggest that o,p'-DDT induces hypertrophy of the MDs and ovarian tissue formation in the left testis. Abnormal MD development may be linked to altered gene expression for sensing estrogens and AMH signals.

Gestational arsenic exposure induces anxiety-like behaviors in F1 female mice by dysregulation of neurological and immunological markers.

BACKGROUND: Arsenic is a harmful heavy metal and a well-known developmental neurotoxicant. Previously, we have reported that gestational arsenic exposure resulted in impaired social behaviors in F1 and F2 male mice. However, little is known about the developmental arsenic exposure on anxiety-like behavior. This study aimed to detect the effect of gestational arsenic exposure on anxiety-like behavior and related gene expressions in 74-week-old F1 female mice. METHOD: Pregnant C3H/HeN mice (F0) were given drinking water containing 85 ppm sodium arsenite (NaAsO2) from gestational day 8 to 18. The control mice were given tap water only. At 74-week-old, open field test was performed, then anxiety and apoptosis-related factors were determined by real_time RT_PCR and immunohistochemical analyses. RESULTS: The arsenite-exposed F1 female mice showed decreased center entry and center time in open field test. In addition, the number of grooming and fecal pallet was significantly increased in the arsenite-exposed F1 female mice compared to the control. Downregulation of brain-derived neurotrophic factor (BDNF), serotonin receptor (5HT1A) and upregulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), interleukin 1 ß (IL-1ß), cyclooxygenase 2 (COX2), caspase-3, Bcl2-associated X protein (Bax) were detected in the prefrontal cortex in the arsenite-exposed F1 female mice. Microglial marker ionized calcium-binding adapter molecule 1 (Iba1)-positive cells were increased in the arsenite-exposed F1 female mice. Moreover, a significantly increased plasma corticosterone level was observed in the arsenic-exposed F1 female mice. CONCLUSIONS: This study suggested that gestational arsenic exposure induced anxiety-like behavior accompanied with dysregulation of neurological and immunological markers, neuroinflammatory responses, neuronal apoptosis, and decreased neurogenesis in the prefrontal cortex of F1 female mice.

A succession of pulmonary microbiota in broilers during the growth cycle.

Respiratory health problems in poultry production are frequent and knotty and thus attract the attention of farmers and researchers. The breakthrough of gene sequencing technology has revealed that healthy lungs harbor rich microbiota, whose succession and homeostasis are closely related to lung health status, suggesting a new idea to explore the mechanism of lung injury in broilers with pulmonary microbiota as the entry point. This study aimed to investigate the succession of pulmonary microbiota in healthy broilers during the growth cycle. Fixed and molecular samples were collected from the lungs of healthy broilers at 1, 3, 14, 21, 28, and 42 d of age. Lung tissue morphology was observed by hematoxylin and eosin staining, and the changes in the composition and diversity of pulmonary microbiota were analyzed using 16S rRNA gene sequencing. The results showed that lung index peaked at 3 d, then decreased with age. No significant change was observed in the α diversity of pulmonary microbiota, while the ß diversity changed regularly with age during the broilers' growth cycle. The relative abundance of dominant bacteria of Firmicutes and their subordinate Lactobacillus increased with age, while the abundance of Proteobacteria decreased with age. The correlation analysis between the abundance of differential bacteria and predicted function showed that dominant bacteria of Firmicutes, Proteobacteria and Lactobacillus were significantly correlated with most functional abundance, indicating that they may involve in lung functional development and physiological activities of broilers. Collectively, these findings suggest that the lung has been colonized with abundant microbiota in broilers when they were just hatched, and their composition changed regularly with day age. The dominant bacteria, Firmicutes, Proteobacteria, and Lactobacillus, play crucial roles in lung function development and physiological activities. It paves the way for further research on the mechanism of pulmonary microbiota-mediated lung injury in broilers.

Melatonin Ameliorates Apoptosis of A549 Cells Exposed to Chicken House PM2.5: A Novel Insight in Poultry Production.

The particulate matter 2.5 (PM2.5) from the chicken production system can cause lung injury and reduce productivity through prolonged breath as it attaches large amounts of harmful substances and microbes. Melatonin has acted to regulate physiological and metabolic disorders and improve growth performance during poultry production. This research would investigate the apoptosis caused by chicken house PM2.5 on lung pulmonary epithelial cells and the protective action of melatonin. Here, the basal epithelial cells of human lung adenocarcinoma (A549 cells) were subjected to PM2.5 from the broiler breeding house to investigate the apoptosis induced by PM2.5 as well as the alleviation of melatonin. The apoptosis was aggravated by PM2.5 (12.5 and 25 µg/mL) substantially, and the expression of Bcl-2, Bad, Bax, PERK, and CHOP increased dramatically after PM2.5 treatment. Additionally, the up-regulation of cleaved caspase-9 and cleaved caspase-3 as well as endoplasmic reticulum stress (ERS)-related proteins, including ATF6 and CHOP, was observed due to PM2.5 exposure. It is worth noting that melatonin could support A549 cells' survival, in which reduced expression of Bax, Bad, cleaved caspase-3, and cleaved caspase-9 appeared. Concurrently, the level of malondialdehyde (MDA) was down-regulated and enhanced the intracellular content of total superoxide dismutase (T-SOD) and catalase (CAT) after treatment by PM2.5 together with melatonin. Collectively, our study underlined that melatonin exerted an anti-apoptotic action on A549 cells by strengthening their antioxidant capacity.

Impact of an email advice service on filtering and refining ophthalmology referrals in England.

PURPOSE: The growing capacity-demand imbalance has necessitated the accelerated digital transformation of eye care services. The role of Oxford Eye Hospital's (OEH) email advice service has become even more relevant in the post-Covid era. We sought to evaluate its impact on referrals to secondary care. METHODS: The consultant-led OEH email advice service primarily targets primary eye care personnel (optometrists and GPs) requiring clinical advice on patient referral. Emails received between September and November 2020 were analysed for demographic data, contents, characteristics, and outcomes. Thematic analysis was performed. A user feedback survey was conducted. RESULTS: A total of 828 emails were received over the 3-month study period (mean 9.1/day). They were predominantly from optometrists (77.9%) and general practitioners (16.1%). Of the 81.0% (671) relating to clinical advice, over half (54.8%) included images from a variety of modalities, and following review, over half (55.5%) were deemed suitable for management in the community, while 36.5% were referred directly to appropriate subspecialty clinics. Only 8.1% required urgent assessment in eye casualty. Thematic analysis showed that this service was most useful for retinal lesions, optical coherence tomography abnormalities, and borderline abnormal optic discs. No adverse events were identified. User feedback was very positive. CONCLUSION: A secure email advice service is a safe and low-maintenance modality that provides direct and efficient two-way communication between primary and secondary eye care professionals. It allows rapid response to clinical queries, referral filtering and refinement, and streamlining of patient referral pathways. Users (predominantly optometrists) were overwhelmingly positive about its usefulness in clinical practice.

Pulmonary microbiota intervention alleviates fine particulate matter-induced lung inflammation in broilers.

Fine particulate matter (PM2.5) released during the livestock industry endangers the respiratory health of animals. Our previous findings suggested that broilers exposed to PM2.5 exhibited lung inflammation and changes in the pulmonary microbiome. Therefore, this study was to investigate whether the pulmonary microbiota plays a causal role in the pathogenesis of PM2.5-induced lung inflammation. We first used antibiotics to establish a pulmonary microbiota intervention broiler model, which showed a significantly reduced total bacterial load in the lungs without affecting the microbiota composition or structure. Based on it, 45 AA broilers of similar body weight were randomly assigned to three groups: control (CON), PM2.5 (PM), and pulmonary microbiota intervention (ABX-PM). From 21 d of age, broilers in the ABX-PM group were intratracheally instilled with antibiotics once a day for 3 d. Meanwhile, broilers in the other two groups were simultaneously instilled with sterile saline. On 24 and 26 d of age, broilers in the PM and ABX-PM groups were intratracheally instilled with PM2.5 suspension to induce lung inflammation, and broilers in the CON group were simultaneously instilled with sterile saline. The lung histomorphology, inflammatory cytokines' expression levels, lung microbiome, and microbial growth conditions were analyzed to determine the effect of the pulmonary microbiota on PM2.5-induced lung inflammation. Broilers in the PM group showed lung histological injury, while broilers in the ABX-PM group had normal lung histomorphology. Furthermore, microbiota intervention significantly reduced mRNA expression levels of interleukin-1ß, tumor necrosis factor-α, interleukin-6, interleukin-8, toll-like receptor 4 and nuclear factor kappa-B. PM2.5 induced significant changes in the ß diversity and structure of the pulmonary microbiota in the PM group. However, no significant changes in microbiota structure were observed in the ABX-PM group. Moreover, the relative abundance of Enterococcus cecorum in the PM group was significantly higher than that in the CON and ABX-PM groups. And sterile bronchoalveolar lavage fluid from the PM group significantly promoted the growth of E. cecorum, indicating that PM2.5 altered the microbiota's growth condition. In conclusion, pulmonary microbiota can affect PM2.5-induced lung inflammation in broilers. PM2.5 can alter the bacterial growth environment and promote dysbiosis, potentially exacerbating inflammation.

Fine particulate matter (PM2.5) in broiler houses has a negative impact on broiler respiratory tracts, and PM2.5 exposure can induce lung inflammation and cause microbiota dysbiosis. The pulmonary microbiota is involved in maintaining immune homeostasis in the lungs, and a variety of lung diseases exhibit microbiota disturbances. However, the correlation between the pulmonary microbiota and PM2.5-induced lung inflammation is poorly understood. This study aimed to investigate whether the pulmonary microbiota influenced PM2.5-induced lung inflammation. We use antibiotics to reduce the quantity of bacteria in the lungs without destroying their composition. PM2.5 was then used to induce lung inflammation in both untreated and intervened pulmonary microbiota broilers. Compared to untreated microbiota broilers, intervened microbiota broilers had less morphological lung tissue injury and lower inflammatory factor expression levels after PM2.5 exposure. Furthermore, the intervened microbiota broilers' microbiota structure remained normal, while the untreated microbiota broilers showed dysbiosis. This dysbiosis is closely linked to changes in the microbial growth environment due to the inflammatory response. This suggested that the pulmonary microbiota affects PM2.5-induced lung inflammation in broilers. Dysbiosis caused by inflammation that alters the conditions for bacterial growth may exacerbate inflammation.

Effects of Oral Exposure to Low-Dose Bisphenol S on Allergic Asthma in Mice.

Bisphenol S (BPS) is increasingly being used as an alternative for bisphenol A; however, its health effects remain unclear. We investigated the effects of oral exposure to low-dose BPS on allergic asthma. C3H/HeJ male mice were intratracheally administered with allergen (ovalbumin (OVA), 1 µg/animal) every 2 weeks from 6 to 11 weeks old. BPS was ingested by drinking water at doses equivalent to 0.04, 0.4, and 4 µg/kg/day. We then examined pulmonary inflammation, airway hyperresponsiveness, serum OVA-specific immunoglobulin (Ig) levels, Th2 cytokine/chemokine production, and mediastinal lymph node (MLN) cell activities. Compared with OVA alone, moderate-dose BPS (BPS-M) with OVA significantly enhanced pulmonary inflammation, airway hyperresponsiveness, and OVA-specific IgE and IgG1. Furthermore, interleukin (IL)-5, IL-13, IL-33, and CCL11/Eotaxin protein levels in the lungs increased. Conversely, these allergic responses were reduced in the high-dose BPS+OVA group. In MLN cells, BPS-M with OVA increased the total cell count and activated antigen-presenting cells including conventional dendritic cell subset (cDC2). After OVA restimulation, cell proliferation and Th2 cytokine production (IL-4, IL-5, and IL-13) in the culture supernatant also increased. Therefore, oral exposure to low-dose BPS may exacerbate allergic asthmatic responses by enhancing Th2-polarized responses and activating the MLN cells.

Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma.

Tris (2-butoxyethyl) phosphate (TBEP) is an organophosphate flame retardant and used as a plasticizer in various household products such as plastics, floor polish, varnish, textiles, furniture, and electronic equipment. However, little is known about the effects of TBEP on the brain and behavior. We aimed to examine the effects of dietary exposure of TBEP on memory functions, their-related genes, and inflammatory molecular markers in the brain of allergic asthmatic mouse models. C3H/HeJSlc male mice were given diet containing TBEP (0.02 (TBEP-L), 0.2 (TBEP-M), or 2 (TBEP-H) µg/kg/day) and ovalbumin (OVA) intratracheally every other week from 5 to 11 weeks old. A novel object recognition test was conducted in each mouse at 11 weeks old. The hippocampi were collected to detect neurological, glia, and immunological molecular markers using the real-time RT-PCR method and immunohistochemical analyses. Mast cells and microglia were examined by toluidine blue staining and ionized calcium-binding adapter molecule (Iba)-1 immunoreactivity, respectively. Impaired discrimination ability was observed in TBEP-H-exposed mice with or without allergen. The mRNA expression levels of N-methyl-D aspartate receptor subunits Nr1 and Nr2b, inflammatory molecular markers tumor necrosis factor-α oxidative stress marker heme oxygenase 1, microglia marker Iba1, and astrocyte marker glial fibrillary acidic protein were significantly increased in TBEP-H-exposed mice with or without allergen. Microglia and mast cells activation were remarkable in TBEP-H-exposed allergic asthmatic mice. Our results indicate that chronic exposure to TBEP with or without allergen impaired object recognition ability accompanied with alteration of molecular expression of neuronal and glial markers and inflammatory markers in the hippocampus of mice. Neuron-glia-mast cells interaction may play a role in TBEP-induced neurobehavioral toxicity.

Early-Life Exposure to Traffic-Related Air Pollutants Induced Anxiety-like Behaviors in Rats via Neurotransmitters and Neurotrophic Factors.

Recent epidemiological studies have reported significantly increasing hospital admission rates for mental disorders such as anxiety and depression, not only in adults but also in children and adolescents, indicating more research is needed for evaluation of the etiology and possible reduction and prevention of these disorders. The aim of the present study was to examine the associations between perinatal exposure to traffic-related air pollutants and anxiety-like behaviors and alterations in neurological and immunological markers in adulthood using a rat model. Sprague Dawley pregnant rats were exposed to clean air (control), diesel exhaust (DE) 101 ± 9 µg/m3 or diesel exhaust origin secondary organic aerosol (DE-SOA) 118 ± 23 µg/m3 from gestational day 14 to postnatal day 21. Anxiety-related behavioral tests including open field tests, elevated plus maze, light/dark transition tests and novelty-induced hypophagia were performed on 10-week-old rats. The hippocampal expression of neurotransmitters, neurotrophic factors, and inflammatory molecular markers was examined by real-time RT-PCR. Anxiety-like behaviors were observed in both male and female rat offspring exposed to DE or DE-SOA. Moreover, serotonin receptor (5HT1A), dopamine receptor (Drd2), brain-derived neurotrophic factor and vascular endothelial growth factor A mRNAs were significantly decreased, whereas interleukin-1ß, cyclooxygenase-2, heme oxygenase-1 mRNAs and microglial activation were significantly increased in both male and female rats. These findings indicate that brain developmental period exposure to traffic-related air pollutants may induce anxiety-like behaviors via modulation of neurotransmitters, neurotrophic factors, and immunological molecular markers, triggering neuroinflammation and microglia activation in rats.

Effect of COVID-19-restrictive measures on ambient particulate matter pollution in Yangon, Myanmar.

BACKGROUND: Particulate matter (PM) is recognized as the most harmful air pollutant to the human health. The Yangon city indeed suffers much from PM-related air pollution. Recent research has interestingly been focused on the novel subject of changes in the air quality associated with the restrictive measures in place during the current coronavirus disease-2019 (COVID-19) pandemic. The first case of COVID-19 in Myanmar was diagnosed on March 23, 2020. In this article, we report on our attempt to evaluate any effects of the COVID-19-restrictive measures on the ambient PM pollution in Yangon. METHODS: We measured the PM concentrations every second for 1 week on four occasions at three study sites with different characteristics; the first occasion was before the start of the COVID-19 pandemic and the remaining three occasions were while the COVID-19-restrictive measures were in place, including Stay-At-Home and Work-From-Home orders. The Pocket PM2.5 Sensor [PRO] designed by the National Institute for Environmental Studies (NIES), Japan, in cooperation with Yaguchi Electric Co., Ltd., (Miyagi, Japan) was used for the measurement of the ambient PM2.5 and PM10 concentrations. RESULTS: The results showed that there was a significant reduction (P < 0.001) in both the PM2.5 and PM10 concentrations while the COVID-19-restrictive measures were in place as compared to the measured values prior to the pandemic. The city experienced a profound improvement in the PM-related air quality from the "unhealthy" category prior to the onset of the COVID-19 pandemic to the "good" category during the pandemic, when the restrictive measures were in place. The percent changes in the PM concentrations varied among the three study sites, with the highest percent reduction noted in a semi-commercial crowded area (84.8% for PM2.5; 88.6% for PM10) and the lowest percent reduction noted in a residential quiet area (15.6% for PM2.5; 12.0% for PM10); the percent reductions also varied among the different occasions during the COVID-19 pandemic that the measurements were made. CONCLUSIONS: We concluded that the restrictive measures which were in effect to combat the COVID-19 pandemic had a positive impact on the ambient PM concentrations. The changes in the PM concentrations are considered to be largely attributable to reduction in anthropogenic emissions as a result of the restrictive measures, although seasonal influences could also have contributed in part. Thus, frequent, once- or twice-weekly Stay-At-Home or Telework campaigns, may be feasible measures to reduce PM-related air pollution. When devising such an action plan, it would be essential to raise the awareness of public about the health risks associated with air pollution and create a social environment in which Telework can be carried out, in order to ensure active compliance by the citizens.

Impact of dietary exposure to low-dose tris(1,3-dichloro-2-propyl)phosphate in allergic asthmatic mice.

OBJECTIVE: Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) is an organophosphorus flame retardant that is an alternative to brominated flame retardants. Although TDCIPP can adversely affect human health, information about its effects on immune and allergic responses is scarce. We aimed to investigate the effects of dietary exposure to TDCIPP using less than the human tolerable daily intake (TDI) in allergic asthmatic mice. METHODS: Male C3H/HeJSlc mice were fed a chow diet containing TDCIPP equivalent to 0.02 µg/kg/day (low; L), 0.2 µg/kg/day (medium; M), or 2 µg/kg/day (high; H) and were intratracheally administered ovalbumin (OVA, 1 µg/animal) every 2 weeks from 5 to 11 weeks of age. RESULTS: In OVA-treated mice, TDCIPP-H exposure tended to enhance pulmonary inflammation compared with vehicle exposure. TDCIPP dose-dependently decreased mRNA level of G protein-coupled estrogen receptor (GPER) in the lungs with or without OVA. OVA + TDCIPP-H treatment tended to increase the total cell number and promoted CD4+ cell activation compared with OVA alone treatment in mediastinal lymph nodes. In splenocytes, an increase in the fraction of Breg cells, but not of total B and T cells, and an increase in IL-5 in cell culture supernatants following OVA re-stimulation in OVA + TDCIPP-H-treated mice was observed compared with OVA-alone-treated mice. Moreover, OVA + TDCIPP-H exposure decreased Gr-1 expression in bone marrow (BM) cells. DISCUSSION: These results suggested that dietary exposure to TDCIPP at TDI level slightly enhances allergic diseases, such as allergic asthma, via GPER regulation at inflamed sites and secondary lymphoid tissue and BM cell alternations.

Environmental cadmium exposure induces kidney tubular and glomerular dysfunction in the Myanmar adults.

Cadmium is an environmental toxic metal and its exposure has become a worldwide public health threat. We aimed to evaluate the exposure assessment of cadmium in people living in Ta Zin Yae Kyaw village of Nyaung Don Township in Ayeyarwady Division, Myanmar and adverse effects of cadmium on the kidneys. Subjects (18-40 years) residing in this village were selected as the exposed group (n = 65) and those living in Kamayut Township in Yangon Division, Myanmar as the control group (n = 65). Spot urine samples were taken for determination of urinary cadmium concentration using graphite-furnace atomic absorption spectrometry (GFAAS) method and adjusted to the concentration of creatinine in urine. To assess the kidney function, urinary ß2-microglobulin level was determined by ELISA, serum creatinine was measured by colorimetric Jaffe method and estimated glomerular filtration rate (eGFR) was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Urine cadmium concentrations were significantly higher in the exposed group (median (Interquartile range): 0.96 (0.19-1.77) µg/g Creatinine) compared to the control (p = 0.036). Urinary ß2-microglobulin levels were significantly higher (p = 0.000) and eGFR was significantly lower in the exposed group (p = 0.013) compared to the control. In addition, urine cadmium level showed significant positive correlation with urinary ß2-microglobulin in all study population (p < 0.01). Positive correlation becomes stronger (p < 0.01) in the exposed group only. For eGFR, significant negative correlation was found in all study population (p < 0.01) and exposed group (p < 0.01). Our findings suggested that environmental cadmium exposure can induce renal dysfunction in both tubular and glomerular functions in apparently healthy human adults.

Effects of maternal exposure to arsenic on social behavior and related gene expression in F2 male mice.

BACKGROUND: Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice. METHODS: Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method. RESULTS: The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1ß (IL-1ß) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice. CONCLUSIONS: These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.

The long-term impact of the Leprosy Post-Exposure Prophylaxis (LPEP) program on leprosy incidence: A modelling study.

BACKGROUND: The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence. METHODOLOGY: The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040. PRINCIPAL FINDINGS: In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme. CONCLUSIONS: The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.

Perinatal Exposure to Diesel Exhaust-Origin Secondary Organic Aerosol Induces Autism-Like Behavior in Rats.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication, poor social interactions, and repetitive behaviors. We aimed to examine autism-like behaviors and related gene expressions in rats exposed to diesel exhaust (DE)-origin secondary organic aerosol (DE-SOA) perinatally. Sprague-Dawley pregnant rats were exposed to clean air (control), DE, and DE-SOA in the exposure chamber from gestational day 14 to postnatal day 21. Behavioral phenotypes of ASD were investigated in 10~13-week-old offspring using a three-chambered social behavior test, social dominance tube test, and marble burying test. Prefrontal cortex was collected to examine molecular analyses including neurological and immunological markers and glutamate concentration, using RT-PCR and ELISA methods. DE-SOA-exposed male and female rats showed poor sociability and social novelty preference, socially dominant behavior, and increased repetitive behavior. Serotonin receptor (5-HT(5B)) and brain-derived neurotrophic factor (BDNF) mRNAs were downregulated whereas interleukin 1 ß (IL-ß) and heme oxygenase 1 (HO-1) mRNAs were upregulated in the prefrontal cortex of male and female rats exposed to DE-SOA. Glutamate concentration was also increased significantly in DE-SOA-exposed male and female rats. Our results indicate that perinatal exposure to DE-SOA may induce autism-like behavior by modulating molecules such as neurological and immunological markers in rats.

Dietary exposure to bisphenol A affects memory function and neuroimmune biomarkers in allergic asthmatic mice.

Bisphenol A (BPA) is a raw material of polycarbonate and epoxy resin. It is used for various household electrical appliances, electronic equipment, office automation equipment, medical equipment, mobile phones, paints for automobiles, internal surface coating of cans, and adhesives for civil engineering and construction. BPA is a well-known endocrine-disrupting chemical, and it was reported that BPA has an adverse effect on the nervous and immune systems. However, BPA-induced memory impairment and changes in neuroimmune biomarkers in the allergic asthmatic subject are not known yet. We aim to investigate the dietary exposure effect of BPA on brain function and biomarkers using allergic an asthmatic mouse model. Five-week-old male C3H/HeJSlc mice were fed two doses of BPA [0.901, 9.01 µg/kg/day] contained chow diet from 5 to 11 weeks old and ovalbumin (OVA) was given by intratracheal instillation every 2 weeks. Memory function was determined by a novel object recognition test. Genes related to memory and immune markers in the hippocampus were investigated with the real-time polymerase chain reaction (RT-PCR) method. In this study, impaired novel object recognition occurred in BPA-exposed mice in the presence of an allergen. Moreover, upregulation of expression level of neuroimmune biomarkers such as N-methyl-D-aspartate receptor, tumor necrosis factor-α, ionized calcium-binding adapter molecule-1, cyclooxygenase-2, and heme oxygenase-1 in the hippocampus was observed in BPA-exposed allergic asthmatic mice. These findings show that BPA exposure can induce neuroinflammation and which triggers impairment of memory function in mice with allergic asthma. Our study indicated that dietary exposure to BPA may affect higher brain functions by modulating neuroimmune biomarkers in allergic asthmatic subjects.

Indoor Formaldehyde Concentration, Personal Formaldehyde Exposure and Clinical Symptoms during Anatomy Dissection Sessions, University of Medicine 1, Yangon.

The formaldehyde (FA) embalming method, the world's most common protocol for the fixation of cadavers, has been consistently used in medical universities in Myanmar. This study was designed to examine the indoor FA concentrations in anatomy dissection rooms, an exposed site, and lecture theater, an unexposed control site, and to access personal exposure levels of FA and clinical symptoms of medical students and instructors. In total, 208 second year medical students (1/2019 batch) and 18 instructors from Department of Anatomy, University of Medicine 1, participated. Thirteen dissection sessions were investigated from February 2019 to January 2020. Diffusive sampling devices were used as air samplers and high-performance liquid chromatography was used for measurement of FA. Average indoor FA concentration of four dissection rooms was 0.43 (0.09-1.22) ppm and all dissection rooms showed indoor concentrations above the occupational exposure limits and short-term exposure limit for general population. Personal FA exposure values were higher than indoor FA concentrations and the instructors (0.68, 0.04-2.11 ppm) had higher exposure than the students (0.44, 0.06-1.72 ppm). Unpleasant odor, eye and nose irritations and inability to concentrate were frequently reported FA-related symptoms, and the students were found to have significantly higher risks (p < 0.05) of having these symptoms during the dissection sessions than during lecture.

Incidence, characteristics, outcomes and confidence in managing posterior capsular rupture during cataract surgery in the UK: an ophthalmology trainees' perspective.

PURPOSE: To examine the incidence, characteristics and outcomes of posterior capsular rupture (PCR) cases amongst the ophthalmology trainees and to evaluate the trainees' confidence in managing PCR. METHODS: A two-staged cross-sectional study was carried out between September 2017 and April 2018 in the North East of England, UK. All ophthalmology trainees were surveyed on their confidence level in managing PCR and the characteristics and outcomes of their PCR cases. RESULTS: Fifteen (71.4%) out of 21 trainees completed the study. The mean number of phacoemulsification was 268.9 ± 250.9 cases (range, 0-705) per trainee. There were 82 (1.9%) cases of PCR reported among 4303 phacoemulsification. PCR occurred most commonly during quadrant removal (44.0%) and cortex removal (21.3%). The best-corrected visual acuity (in logMAR) improved significantly from 0.47 ± 0.32 preoperatively to 0.20 ± 0.19 postoperatively (p < 0.001). The supervising consultant took over 80.5% of the PCR cases. The PCR rate decreased significantly from 3.1% at 0-100 cases to 0.6% at 301-400 cases (p = 0.004) and to 0.4% at >500 cases (p = 0.005). Confidence in managing PCR (without supervision) improved from 0% (9/9) at junior level to 50% (3/6) at senior level, and the average number of anterior vitrectomies performed was 0.6 ± 0.9 (range: 0.0-2.0). CONCLUSIONS: We observed a low PCR rate among the trainees in our region, with the majority of cases achieving good visual outcome. A significant reduction in PCR rate was observed at the threshold of >500 cases. There is however a lack of confidence among trainees in managing PCR, highlighting the need for devising new training strategies in this area.

Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme.

BACKGROUND: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. METHODS: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. FINDINGS: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. INTERPRETATION: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established. FUNDING: Novartis Foundation.