Genotoxicity and cytotoxicity of antineoplastic drugs at environmentally relevant concentrations after long-term exposure.

Introduction: 5-fluorouracil (5-FU) and methotrexate (MTX) are the antineoplastic drugs most commonly used worldwide. Considered cytotoxic, these pharmaceuticals exhibit low specificity, causing damage not only to cancer cells but also to healthy cells in organisms. After being consumed and metabolized, these drugs are excreted through urine and feces, followed by wastewater treatment. However, conventional treatments do not have the capacity to completely remove these substances, risking their introduction into freshwater systems. This could pose a risk to human health even at low concentrations. Aims: Thus, the present study aimed to investigate the genotoxicity, cytotoxicity, and mutagenicity of 5-FU and MTX at environmentally relevant concentrations after a long-term exposure, using adult male rats as an experimental model. Methods: Male Wistar rats (70 days old) were distributed into 4 groups (n = 10/group): control, received only vehicle; MTX, received methotrexate at 10ngL-1; 5-FU received 5-fluorouracil at 10ngL-1; and MTX + 5-FU, received a combination of MTX and 5-FU at 10ngL-1 each. The period of exposure was from postnatal day (PND) 70 to PND 160, through drinking water. After that, the animals were euthanized and the samples (liver, testis, femoral bone marrow, and peripheral blood) were obtained. Results: Increased DNA fragmentation was observed in the peripheral blood, liver, and testis, altering the parameters of the tail moment and tail intensity in the Comet assay. Besides, the change in the ratio between PCE and NCE indicates bone marrow suppression. Conclusion: These findings warn the adverse effects for the general population worldwide chronically exposed to these drugs at trace concentration unintentionally.

Neonatal near-miss audits: a systematic review and a call to action.

BACKGROUND: Neonatal near-miss (NNM) can be considered as an end of a spectrum that includes stillbirths and neonatal deaths. Clinical audits of NNM might reduce perinatal adverse outcomes. The aim of this review is to evaluate the effectiveness of NNM audits for reducing perinatal mortality and morbidity and explore related contextual factors. METHODS: PubMed, Embase, Scopus, CINAHL, LILACS and SciELO were searched in February/2023. Randomized and observational studies of NNM clinical audits were included without restrictions on setting, publication date or language. PRIMARY OUTCOMES: perinatal mortality, morbidity and NNM. SECONDARY OUTCOMES: factors contributing to NNM and measures of quality of care. Study characteristics, methodological quality and outcome were extracted and assessed by two independent reviewers. Narrative synthesis was performed. RESULTS: Of 3081 titles and abstracts screened, 36 articles had full-text review. Two studies identified, rated, and classified contributing care factors and generated recommendations to improve the quality of care. No study reported the primary outcomes for the review (change in perinatal mortality, morbidity and NNM rates resulting from an audit process), thus precluding meta-analysis. Three studies were multidisciplinary NNM audits and were assessed for additional contextual factors. CONCLUSION: There was little data available to determine the effectiveness of clinical audits of NNM. While trials randomised at patient level to test our research question would be difficult or unethical for both NNM and perinatal death audits, other strategies such as large, well-designed before-and-after studies within services or comparisons between services could contribute evidence. This review supports a Call to Action for NNM audits. Adoption of formal audit methodology, standardised NNM definitions, evaluation of parent's engagement and measurement of the effectiveness of quality improvement cycles for improving outcomes are needed.

Cannabidiol in the prelimbic cortex modulates the comorbid condition between the chronic neuropathic pain and depression-like behaviour in rats: The role of medial prefrontal cortex 5-HT1A and CB1 receptors.

The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a cerebral division that is putatively implicated in the chronic pain and depression. We investigated the activity of PrL cortex neurons in Wistar rats that underwent chronic constriction injury (CCI) of sciatic nerve and were further subjected to the forced swimming (FS) test and mechanical allodynia (by von Frey test). The effect of blockade of synapses with cobalt chloride (CoCl2), and the treatment of the PrL cortex with cannabidiol (CBD), the CB1 receptor antagonist AM251 and the 5-HT1A receptor antagonist WAY-100635 were also investigated. Our results showed that CoCl2 decreased the time spent immobile during the FS test but did not alter mechanical allodynia. CBD (at 15, 30 and 60 nmol) in the PrL cortex also decreased the frequency and duration of immobility; however, only the dose of 30 nmol of CBD attenuated mechanical allodynia in rats with chronic NP. AM251 and WAY-100635 in the PrL cortex attenuated the antidepressive and analgesic effect caused by CBD but did not alter the immobility and the mechanical allodynia when administered alone. These data show that the PrL cortex is part of the neural substrate underlying the comorbidity between NP and depression. Also, the previous blockade of CB1 cannabinoid receptors and 5-HT1A serotonergic receptors in the PrL cortex attenuated the antidepressive and analgesics effect of the CBD. They also suggest that CBD could be a potential medicine for the treatment of depressive and pain symptoms in patients with chronic NP/depression comorbidity.

Xenograft materials in maxillary sinus floor elevation surgery: a systematic review with network meta-analyses.

A systematic review and network meta-analysis was conducted to compare different commercially available xenograft materials used in maxillary sinus floor elevation surgery (MSFES). Embase, PubMed, the Cochrane Library, Web of Science, Scopus, LILACS, and grey literature were searched up to 13 July 2020. Only randomised controlled trials (RCTs) were included. A frequentist network meta-analysis using a random effects model compared different commercially available xenograft materials. The primary outcomes were the percentage of newly-formed bone and residual bone-substitute rate. Both were measured by histomorphometric analysis from bone biopsies obtained during preparation of the implant site. Of the 659 studies initially identified, 11 involving 242 MSFES were included in the quantitative analyses. A total of six bone-substitute materials were analysed (Bio-Oss® (Geistlich Pharma), InduCera® Dual Coat, Lumina-Bone Porous® (Critéria), Osseous® (SIN - Sistema de Implantes Nacional), THE Graft® (Purgo Biologics), and Osteoplant Osteoxenon® (Bioteck)). The P-score estimation showed that Osteoplant Osteoxenon® produced the most newly-formed bone and reabsorbed faster than other xenograft materials after six months. The combination of Bio-Oss® plus bone marrow aspirate concentrate (BMAC) significantly increased the percentage of newly-formed bone compared with Bio-Oss® alone. In contrast, the addition of Emdogain® (Straumann) and leucocyte and platelet-rich fibrin (L-PRF) to Bio-Oss® did not significantly improve the amount of regenerated bone. Study-level data indicated that the percentage of newly-formed bone differs among commercially available xenograft materials. Osteoplant Osteoxenon® seems to result in the highest amount of new bone in MSFES.

Cardiac synchronism assessment by myocardial perfusion imaging in patients with cardiac resynchronization therapy

BACKGROUND: the treatment of heart failure has undergone major therapeutic advances in recent decades, among them, cardiac resynchronization therapy (CRT), a strategy capable of reducing symptoms, hospitalization and mortality. It is known that up to 30% of patients undergoing CRT do not have a satisfactory response, based on current selection criteria. Purpose: Myocardial perfusion scintigraphy by Gated-SPECT technique (Gated-SPECT) can provide important information such as mechanical timing, region of last mechanical activation and fibrosis which are very useful in the best selection of who would really benefit from this device. OBJECTIVE: to evaluate the presence of improvement in the mechanical synchronism of the left ventricle (LV) in patients with CRT, using the Synctool software used in the Gated-SPECT, as well as to correlate the data obtained with clinical improvement, defined by reduction of at least 1 New York Heart Association class and reduction of at least 5 points in the Minessota Living With Heart Failure Questionnaire (MLHFQ), and also correlate to other epidemiological, clinical, electrocardiographic and perfusional variables. METHODS: 31 patients (p) with CRT underwent Gated-SPECT at 2 different times: CRT on and off. A quality of life questionnaire was also applied and clinical data before and after implantation of the device were collected. RESULTS: improved synchronism with reduced histogram bandwidth (BWH) (215.6 ± 74.7 ° vs. 149.9 ± 67.9 °; p <0.001) and phase standard deviation (SD) (65, 3 ± 21.7 ° vs. 53.1 ± 22.7 °; p <0.001), after CRT is turned on. Patients who presented synchrony improvement had a higher frequency of clinical improvement (p = 0.026) and obtained lower values of LV end diastolic volume (204.4 ± 100.4 ml vs. 304.3 ± 77.2 ml; p = 0.028) and LV end-systolic volume (120.2 ± 88.8 ml vs. 197.5 ± 51.6 ml; p = 0.026). When clinical improvement was examined, 23 (74.1%) p were considered as responders and 8 (25.9%) as non-responders. Responders showed a significant increase in the LV ejection fraction (38.4 ± 14.1 vs. 47.9 ± 15.3; p <0.001). Non-responders had a higher mean of myocardial involvement by fibrosis (12.9 ± 5.5% vs. 5.7 ± 8.4%; p = 0.033) and higher frequency of fibrosis in the lateral and inferolateral walls (50% vs. 8.7%; p = 0.026), presented an even lower percentage of localization of the region of last mechanical activation (LMA) in the lateral and inferolateral walls (12.5% vs 56.5%; p = 0.045), thus assuming a discordant position between fibrosis and the CRT pacing electrode in the LV. CONCLUSION: Synctoll software are very useful to predict the evaluation of patients with CRT wich was able to improve the mechanical timing of the LV. Improvement in mechanical synchrony is associated with clinical improvement and marked reverse remodeling. Presence of fibrosis and region of last mechanical activation in the lateral and inferolateral walls are predictive factors of response to CRT.

Antibacterial effects of the lectin from pomegranate sarcotesta (PgTeL) against Listeria monocytogenes.

AIMS: To investigate the effects of the lectin from Punica granatum sarcotesta (PgTeL) on growth, viability, cell structure, biofilm formation and chitinase activity of Listeria monocytogenes. In addition, the effect of PgTeL on the adhesion and invasion of human cells (HeLa) was determined. METHODS AND RESULTS: PgTeL showed bacteriostatic and bactericidal effects on the strains L. monocytogenes N53-1 and EGD-e, causing morphometric alterations, cell aggregation, strong deformation and cell disruption. PgTeL inhibited biofilm formation by EGD-e and N53-1 and also interfered with the adhesion and invasion processes of EGD-e and N53-1 in HeLa cells. Finally, the chitinase activity of L. monocytogenes EGD-e was reduced in the presence of PgTeL, which can be involved in the inhibition of adhesion process. CONCLUSION: PgTeL is an antibacterial agent against L. monocytogenes, inhibiting growth and promoting cell death, as well as impairing biofilm formation and bacterial adhesion and invasion into human cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The results stimulate future investigations on the potential of PgTeL for protection of contamination in food products.

Indomethacin attenuates mechanical allodynia during the organization but not the maintenance of the peripheral neuropathic pain induced by nervus ischiadicus chronic constriction injury.

The neurochemical mechanisms underlying neuropathic pain (NP) are related to peripheral and central sensitization caused by the release of inflammatory mediators in the peripheral damaged tissue and ectopic discharges from the injured nerve, leading to a hyperexcitable state of spinal dorsal horn neurons. The aim of this work was to clarify the role played by cyclooxygenase (COX) in the lesioned peripheral nerve in the development and maintenance of NP by evaluating at which moment the non-steroidal anti-inflammatory drug indomethacin, a non-selective COX inhibitor, attenuated mechanical allodynia after placing one loose ligature around the nervus ischiadicus, an adaptation of Bennett and Xie's model in rodents. NP was induced in male Wistar rats by subjecting them to chronic constriction injury (CCI) of the nervus ischiadicus, placing one loose ligature around the peripheral nerve, and a sham surgery (without CCI) was used as control. Indomethacin (2 mg/kg) or vehicle was intraperitoneally and acutely administered in each group of rats and at different time windows (1, 2, 4, 7, 14, 21, and 28 days) after the CCI or sham surgical procedures, followed by von Frey's test for 30 min. The data showed that indomethacin decreased the mechanical allodynia threshold of rats on the first, second, and fourth days after CCI (P<0.05). These findings suggested that inflammatory mechanisms are involved in the induction of NP and that COX-1 and COX-2 are involved in the induction but not in the maintenance of NP.

Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients.

BACKGROUND: Xeroderma pigmentosum (XP) patients present a high risk of developing skin cancer and other complications at an early age. This disease is characterized by mutations in the genes related to the DNA repair system. OBJECTIVES: To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP. METHODS: Twenty-seven families were screened for germline variants in eight XP-related genes. RESULTS: All patients (N = 32) were diagnosed with bi-allelic germline pathogenic or potentially pathogenic variants, including nine variants previously undescribed. The c.2251-1G>C XPC pathogenic variant, reported as the founder mutation in Comorian and Pakistani patients, was observed in 15 cases in homozygous or compound heterozygous. Seven homozygous patients for POLH/XPV variants developed their symptoms by an average age of 7.7 years. ERCC2/XPD, DDB2/XPE and ERCC5/XPG variants were found in a few patients. Aside from melanoma and non-melanoma skin tumours, a set of patients developed skin sebaceous carcinoma, leiomyosarcoma, angiosarcoma, mucoepidermoid carcinoma, gastric adenocarcinoma and serous ovarian carcinoma. CONCLUSIONS: We reported a high frequency of XPC variants in 32 XP Brazilian patients. Nine new variants in XP-related genes, unexpected non-skin cancer lesions and an anticipation of the clinical manifestation in POLH/XPV cases were also described.

Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis.

In this systematic review and network meta-analysis including only randomized clinical trials (RCTs), different grafting materials used in alveolar ridge preservation after tooth extraction were analysed, focusing on histomorphometric new bone formation (NBF) in core biopsies obtained during implant placement. The PubMed, Embase, Cochrane Library, Web of Science, Scopus, and LILACS databases, as well as the grey literature, were searched for published and unpublished trials (from database inception to January 14, 2019). The primary outcome was the percentage of NBF. The secondary outcomes were the percentage of residual biomaterial and the percentage of soft tissue. An arm-based network meta-analysis was performed. The rank of intervention efficacy was obtained to measure the probability of each biomaterial being ranked first across all interventions. A total of 1526 studies were found, of which 38 were included for quantitative analysis. Three trials were rated as having a high risk of bias and 35 trials as having an unclear risk of bias. The network meta-analysis showed that nine grafting materials decreased NBF and 25 did not decrease NBF. The grafting material with the highest amount of NBF was plasma rich in growth factors. Due to the lack of studies with a low risk of bias, further RCTs are needed for definitive conclusions.

Indomethacin attenuates mechanical allodynia during the organization but not the maintenance of the peripheral neuropathic pain induced by nervus ischiadicus chronic constriction injury

The neurochemical mechanisms underlying neuropathic pain (NP) are related to peripheral and central sensitization caused by the release of inflammatory mediators in the peripheral damaged tissue and ectopic discharges from the injured nerve, leading to a hyperexcitable state of spinal dorsal horn neurons. The aim of this work was to clarify the role played by cyclooxygenase (COX) in the lesioned peripheral nerve in the development and maintenance of NP by evaluating at which moment the non-steroidal anti-inflammatory drug indomethacin, a non-selective COX inhibitor, attenuated mechanical allodynia after placing one loose ligature around the nervus ischiadicus, an adaptation of Bennett and Xie's model in rodents. NP was induced in male Wistar rats by subjecting them to chronic constriction injury (CCI) of the nervus ischiadicus, placing one loose ligature around the peripheral nerve, and a sham surgery (without CCI) was used as control. Indomethacin (2 mg/kg) or vehicle was intraperitoneally and acutely administered in each group of rats and at different time windows (1, 2, 4, 7, 14, 21, and 28 days) after the CCI or sham surgical procedures, followed by von Frey's test for 30 min. The data showed that indomethacin decreased the mechanical allodynia threshold of rats on the first, second, and fourth days after CCI (P<0.05). These findings suggested that inflammatory mechanisms are involved in the induction of NP and that COX-1 and COX-2 are involved in the induction but not in the maintenance of NP.

Miopericardite tuberculosa associado a QT longo e torsades de pointes: relato de caso / Tuberculous myopericarditis associated with long QT and torsades de pointes: case report

INTRODUÇÃO: A tuberculose cardíaca é uma doença rara Estima-se que 1% de todos os casos de tuberculose têm envolvimento cardíaco produzido por disseminação linfática, contígua do pericárdio ou por via hematogênica. Miocardite tuberculosa pode permanecer clinicamente assintomática (com diagnóstico feito em autópsia), ou pode se apresentar com morte, arritmias ventriculares intratáveis, síndrome do QT longo, bloqueio cardíaco ou insuficiência cardíaca. Complicações cardíacas, como taquiarritmias ventriculares, são ainda mais raras, mas são potencialmente tratáveis se reconhecimento imediato. RELATO DE CASO: S.A.F.R., 55 anos, sexo feminino, com dispneia e palpitações há cerca de três meses da admissão no pronto socorro. ECG evidenciando QT longo (figura 1) Ecocardiograma mostrou derrame pericárdico com repercussão hemodinâmica. Realizada drenagem de Marfan de urgência. No 2 dia de pós-operatório, apresentou Taquicardia Ventricular (TV) Sustentada Monomórfica Instável. Após cardioversão elétrica, evoluiu com múltiplos episódios de TV com Torsades de Pointes. A arritmia ventricular foi atribuída a QT longo congênito. Medicada com lidocaína EV, passado fio de marcapasso provisório com persistência da arritmia. Análise do líquido pericárdico evidenciou adenosina deaminase de 110 U/l e ressonância magnética (figura 2) apresentando edema miocárdico e sinais de processo inflamatório. Feito diagnóstico de Miopericardite tuberculósica e iniciado esquema RIPE. Após 15 dias, observou-se normalização do intervalo QT e desaparecimento dos sintomas e das arritmias ventriculares, sem recidiva de derrame pericárdico. Evoluiu na sequência com quadro séptico, por endocardite infecciosa, trombo em fio de marcapasso e insuficiência tricúspide. Foi submetida a cirurgia para retirada de fio de marca-passo provisório e troca valvar tricúspide de urgência, evoluindo a óbito no pós-operatório. CONCLUSÃO: O QT longo, inicialmente pensado como congênito, foi considerado a causa das arritmias. O papel da inflamação na gênese do QT longo tem sido descrito e foi comprovado neste caso, pela normalização do intervalo e desaparecimento das arritmias com o tratamento específico da tuberculose. Alto grau de suspeição é importante para diagnóstico precoce, já que alguns casos de miocardite tuberculosa foram relatados no último anos na literatura inglesa, francesa e espanhola, todos eles diagnosticados na necropsia. A terapia antituberculose pode resultar em sucesso com regressão da doença e resolução de arritmias malignas. (AU)

Fast and simultaneous doping of Sr0.9-x-y-zCa0.1In2O4:(xEu3+, yTm3+, zTb3+) superstructure by ultrasonic spray pyrolysis.

In the present work, Sr0.9-x-y-zCa0.1In2O4:(xEu3+, yTm3+, zTb3+) particles were synthesized by the ultrasonic spray pyrolysis (USP) method to obtain a single-phase white phosphorus formed by six different cations in solution within the lattice (superstructure). The samples were also structurally and morphologically characterized by X-ray diffraction (XRD) techniques and by field emission scanning electron microscopy (FE-SEM). The photoluminescent behavior and the characteristics of the emitted colors were studied by the variation in the co-doping of the rare earth elements. The Sr0.9Ca0.1In2O4 sample showed a near blue color emission, but all co-doped samples showed emission in white with very close chromaticity coordinates to the standard white (x = 0.33 and y = 0.33). The Tm3+ → Tb3+ (ET1), Tm3+ → Eu3+ (ET2) and Tb3+ → Eu3+ (ET3) Energy Transfers were proposed and are considered necessary for adjusting and controlling the desired color properties.

Randomized double-blind clinical trial evaluation of bone healing after third molar surgery with the use of leukocyte- and platelet-rich fibrin.

The objective of this study was to evaluate the use of leukocyte- and platelet-rich fibrin (L-PRF) in bone healing after mandibular third molar extraction. In this prospective, double-blind, split-mouth study, 34 extractions were performed. On one side, the socket was sutured primarily (control side); on the other side, L-PRF was inserted before suturing. The patients were assessed for postoperative bone regeneration, pain and soft tissue healing. The primary outcome was bone regeneration, which was performed through tomographic evaluation in the immediate postoperative period and 3 months after the procedure. The ITK-SNAP software was used for image evaluation by the intensity of grey of each voxel. Pain was analysed using a visual analogue scale (VAS), and soft tissue healing was analysed both based on the modified healing index of Landry et al., and by comparing pre- and postoperative periodontal probing at the distal of the lower second molar. The application of L-PRF improved bone density, which was higher in test group (p=0.007). There was no statistical difference related to pain or soft tissue between the groups (p>0.05). There was evidence for improved bone healing in response to L-PRF. However, to better understand the effect of L-PRF more clinical trials with larger samples are necessary.

Platelet-rich fibrin in oral surgical procedures: a systematic review and meta-analysis.

The effect of platelet-rich fibrin (PRF) in enhancing the healing after oral surgical interventions is still a matter of debate. The purpose of this study was to identify instances where PRF has been shown to be effective in oral surgical procedures. A comprehensive literature search was performed up to 2017 on PubMed/MEDLINE, Cochrane Library, Web of Science, Scopus and LILACS databases and grey literature. The full-text of potentially relevant studies were reviewed and only randomized clinical trials (RCTs) were included. A total of 559 studies were found, of which 30 were included for qualitative analysis and 13 for quantitative analysis. Three review authors assessed the risk of bias independently. The available literature suggests that PRF has a positive effect in improving alveolar preservation on extraction sockets and around dental implants. The qualitative analysis showed a significantly better effect of PRF in promoting bone regeneration for alveolar cleft reconstruction. The meta-analysis for third molar surgery showed a decrease in prevalence of alveolar osteitis. PRF increased implant stability 1 week and 1 month after surgery (P=0.0005 and 0.0003). Due to the lack of studies with low risk of bias and a limited number of patients available, further RCTs are needed to confirm these results.

A Multicentric Brazilian Investigative Study of Copy Number Variations in Patients with Congenital Anomalies and Intellectual Disability.

Genomic imbalances are the most common cause of congenital anomalies (CA) and intellectual disability (ID). The aims of this study were to identify copy number variations (CNVs) in 416 patients with CA and ID from 5 different genetics centers within 4 different states by using the Multiplex Ligation-dependent Probe Amplification (MLPA) technique and to apply the chromosomal microarray (CMA) methodology in selected cases. The samples were analyzed by MLPA kits P064, P036, P070 and P250. Positive results were found in 97/416 (23.3%) patients. CMA was applied in 14 selected cases. In 6/14 (42.85%) patients, CMA detected other copy number variations not detected by the MLPA studies. Although CMA is indispensable for genotype refinement, the technique is still unfeasible in some countries as a routine analysis due to economic and technical limitations. In these cases, clinical evaluation followed by karyotyping and MLPA analysis is a helpful and affordable solution for diagnostic purposes.

Intestinal cell migration damage induced by enteropathogenic Escherichia coli strains.

Epithelial cell migration is an essential response to enteric pathogens such as enteropathogenic Escherichia coli (EPEC). This study aimed to investigate the effects of EPEC infection on intestinal epithelial cell migration in vitro, as well as the involvement of type III secretion system (T3SS) and Rho GTPases. Crypt intestinal epithelial cells (IEC-6) were infected with EPEC strains (E2348/69, ΔescF, and the LDI001 strain isolated from a malnourished Brazilian child) and commensal E. coli HS. Wound migration and cell death assays were performed at different time-points. Transcription and expression of Rho GTPases were evaluated using real-time PCR and western blotting. Overall, EPEC E2348/69 reduced migration and increased apoptosis and necrosis levels compared to EPEC LDI001 and E. coli HS strains. Moreover, EPEC LDI001 impaired cell migration at a higher level than E. coli HS and increased necrosis after 24 hours compared to the control group. The different profiles of virulence genes between the two wild-type EPEC strains, characterized by the absence of espL and nleE genes in the LDI001, might explain the phenotypic results, playing significant roles on cell migration impairment and cell death-related events. Moreover, the type III secretion system is determinant for the inhibition of intestinal epithelial cell migration by EPEC 2348/69, as its deletion prevented the effect. Active Rac1 concentrations were increased in E2348/69 and LDI001-infected cells, while the T3SS-deficient strain did not demonstrate this activation. This study contributes with valuable insight to characterize the mechanisms involved in the impairment of intestinal cell migration induced by EPEC.

Critical Role of Zinc in a New Murine Model of Enterotoxigenic Escherichia coli Diarrhea.

Enterotoxigenic Escherichia coli (ETEC) is a major cause of traveler's diarrhea as well as of endemic diarrhea and stunting in children in developing areas. However, a small-mammal model has been badly needed to better understand and assess mechanisms, vaccines, and interventions. We report a murine model of ETEC diarrhea, weight loss, and enteropathy and investigate the role of zinc in the outcomes. ETEC strains producing heat-labile toxins (LT) and heat-stable toxins (ST) that were given to weaned C57BL/6 mice after antibiotic disruption of normal microbiota caused growth impairment, watery diarrhea, heavy stool shedding, and mild to moderate intestinal inflammation, the latter being worse with zinc deficiency. Zinc treatment promoted growth in zinc-deficient infected mice, and subinhibitory levels of zinc reduced expression of ETEC virulence genes cfa1, cexE, sta2, and degP but not of eltA in vitro Zinc supplementation increased shedding and the ileal burden of wild-type (WT) ETEC but decreased shedding and the tissue burden of LT knockout (LTKO) ETEC. LTKO ETEC-infected mice had delayed disease onset and also had less inflammation by fecal myeloperoxidase (MPO) assessment. These findings provide a new murine model of ETEC infection that can help elucidate mechanisms of growth, diarrhea, and inflammatory responses as well as potential vaccines and interventions.

Organic solvent exposure and contrast sensitivity: comparing men and women.

The goal of this study was to compare the visual contrast sensitivity (CS) of men and women exposed and not exposed to organic solvents. Forty-six volunteers of both genders aged between 18 and 41 years (mean±SD=27.72±6.28) participated. Gas station attendants were exposed to gas containing 46.30 ppm of solvents at a temperature of 304±274.39 K, humidity of 62.25±7.59% and ventilation of 0.69±0.46 m/s (a passive gas chromatography-based sampling method was used considering the microclimate variables). Visual CS was measured via the psychophysical method of two-alternative forced choice using vertical sinusoidal gratings with spatial frequencies of 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, and 16.0 cpd (cycles per degree) and an average luminance of 34.4 cd/m2. The results showed that visual CS was significantly lower (P<0.05) in the following groups: i) exposed men compared to unexposed men at frequencies of 0.2, 0.5, 1.0, and 2.0 cpd; ii) exposed women compared to unexposed women at a frequency of 5.0 cpd; and iii) exposed women compared to exposed men at a frequency of 0.5 cpd, even at exposures below the tolerance limit (300 ppm). These results suggest that the visual CS of exposed men was impaired over a wider range of spatial frequencies than that of exposed women. This difference may have been due to the higher body fat content of women compared to that of men, suggesting that body fat in women can serve as a protective factor against neurotoxic effects.

Comparison of the accuracy of maxillary position between conventional model surgery and virtual surgical planning.

The aim of this study was to determine whether virtual surgical planning (VSP) is an accurate method for positioning the maxilla when compared to conventional articulator model surgery (CMS), through the superimposition of computed tomography (CT) images. This retrospective study included the records of 30 adult patients submitted to bimaxillary orthognathic surgery. Two groups were created according to the treatment planning performed: CMS and VSP. The treatment planning protocol was the same for all patients. Pre- and postoperative CT images were superimposed and the linear distances between upper jaw reference points were measured. Measurements were then compared to the treatment planning, and the difference in accuracy between CMS and VSP was determined using the t-test for independent samples. The success criterion adopted was a mean linear difference of <2mm. The mean linear difference between planned and obtained movements for CMS was 1.27±1.05mm, and for VSP was 1.20±1.08mm. With CMS, 80% of overlapping reference points had a difference of <2mm, while for VSP this value was 83.6%. There was no statistically significant difference between the two techniques regarding accuracy (P>0.05).