Melatonin protects against methotrexate hepatotoxicity in young rats: Impact of PI3K/Akt/mTOR signaling.

With the improvement in children's acute lymphoblastic leukemia (ALL) care, the survival rate in children ALL has improved much. Methotrexate (MTX) plays an essential role in the success of children's ALL treatment. Since hepatotoxicity is commonly reported in individuals treated with intravenous or oral MTX, our study further examined the hepatic effect following intrathecal MTX treatment, which is an essential treatment for leukemia patients. Specifically, we examined the pathogenesis of MTX hepatotoxicity in young rats and explored the impact of melatonin treatment in protection against MTX hepatotoxicity. Successfully, we found that melatonin was able to protect against MTX hepatotoxicity.

Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process.

With the improvement of the survival rate of acute lymphoblastic leukemia (ALL) in children, some children ALL survivors reveal inferior intellectual and cognition outcome. Methotrexate (MTX), while serving as an essential component in ALL treatment, has been reported to be related to various neurologic sequelae. Using combined intrathecal (IT) and intraperitoneal (IP) MTX model, we had demonstrated impaired spatial memory function in developing rats, which can be rescued by melatonin treatment. To elucidate the impact of MTX treatment on the epigenetic modifications of the myelination process, we examined the change of neurotrophin and myelination-related transcriptomes in the present study and found combined IT and IP MTX treatment resulted in altered epigenetic modification on the myelination process, mainly in the hippocampus. Further, melatonin can restore the MTX effect through alterations of the epigenetic pathways.

Brain imaging findings in Parkinson disease with Pisa syndrome: A case report.

RATIONALE: The Pisa syndrome (PS) is defined as a kind of reversible postural deformity which causes a lateral trunk flexion of 10 degrees or more. A prevalence of approximately 7.4% to 10.3% of patients with Parkinson disease (PD) also have PS. Though unbalanced function of the basal ganglia network and impaired visual-spatial functions including parietal cortices in PS is known, the pathophysiology of PS remains to be unclear. PATIENT CONCERNS: A 67-year-old male patient with PD visited our Rehabilitation outpatient department because of his trunk which involuntarily deviated to the left side when he stood up. DIAGNOSES: Based on the history, physical examination, X-ray images, Tc-99m brain TRODAT-1 single-photon emission computed tomography (SPECT), and regional cerebral perfusion Tc-99m ethyl cysteinate dimer SPECT, the patient was diagnosed with PD with PS. INTERVENTIONS: The patient refused our recommendation of admission for pharmaceutical treatment due to personal reasons and was only willing to accept physical training programs at our outpatient department. OUTCOMES: We arranged functional neuroimaging of the brain to survey possible neurologic deficits. The patient's images of ethyl cysteinate dimer SPECT and TRODAT SPECT showed abnormalities, including hypoperfusion and diminished dopamine transporter uptake, in the areas of the basal ganglia network and other brain regions. LESSONS: Based on previous literature and the imaging of our patient, we hypothesize that PS results from unbalanced function of the basal ganglia network and impaired visual-spatial functions of bilateral parietal cortices.

Proactive COVID-19 Infection Prevention Measures in a Hyperbaric Oxygen Therapy Center.

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China in December 2019 and its subsequent global spread, Taiwan has been combatting this pandemic. COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As SARS-CoV-2 can be transmitted through droplets and aerosols, we cannot ignore the risk of transmission during hyperbaric oxygen therapy (HBOT). Our hyperbaric oxygen therapy center prioritizes preventing the spread of COVID-19 and maintaining operation for the patients during the pandemic. The aim of this article is to share the protocol that we have adopted in our hyperbaric oxygen therapy center to help prevent the spread of COVID-19.

Melatonin rescued methotrexate-induced spatial deficit and hyperhomocysteinemia and increased asymmetric dimethylarginine in plasma and dorsal hippocampus in developing rats.

AIMS: With the improvement of the survival rates in children acute lymphoblastic leukemia (ALL), some children ALL survivors show impaired cognitive function. Methotrexate (MTX), an essential component in ALL treatment, has been reported to be related to neurologic sequelae and to increased oxidative stress through its interactions with enzymes in the folate pathway. Asymmetric dimethylarginine (ADMA) is the main endogenous inhibitor of nitric oxide synthase, and increased ADMA may result from increased oxidants. Melatonin is an antioxidant; however, its role in MTX neuropathy is not well studied. We developed a rat model mimicking child ALL treatment to explore peripheral and central homocysteine and ADMA regulation after MTX and found potential treatment choice. MAIN METHODS: Preweaning male Sprague-Dawley rats were used in this study. Experiment 1 evaluated spatial performance in rats with intrathecal (IT) MTX, intraperitoneal (IP) MTX, or combined IT and IP MTX, protocols mimicking ALL treatment in children. Experiment 2 focused on rats with combined IT and IP MTX, evaluating spatial performance and plasma and dorsal hippocampal homocysteine and ADMA levels, their regulation, and the protective effect of melatonin. KEY FINDINGS: Combined IT and IP MTX treatment caused in spatial deficits in developing rats, and melatonin restored the spatial performance. Alterations in peripheral and central homocysteine and ADMA concentrations and their regulation were found and could be alleviated by melatonin treatment. SIGNIFICANCES: Combined IP and IT MTX treatment caused spatial deficits in developing rats. Melatonin could restore spatial performance through alleviating the effects on the imbalance of oxidative stress.

Utility of 18F-FDG uptake in various regions of Waldeyer's ring to differentiate benign from malignant lesions in the midline roof of the nasopharynx.

PURPOSE: Lymphoid hyperplasia is not uncommon in the midline roof of the nasopharynx. Most nasopharyngeal carcinoma patients present with primary tumors in the midline of the nasopharynx. The aim of this study was to evaluate the efficacy of 2-[fluorine-18] fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/computed tomography (CT) to differentiate between benign and malignant lesions in the midline roof of the nasopharynx. MATERIALS AND METHODS: The data from the (18)F-FDG PET/CT images of 4846 participants were analyzed. Visual uptake, the lesions' standard uptake values (SUVs), and any abnormalities on the PET/CT images were evaluated. RESULTS: Sixty-six individuals with benign lesions and 25 with nasopharyngeal carcinoma were included in the analysis. The participants with benign and malignant lesions displayed increased (18)F-FDG uptake (SUV; mean±SD) in the midline roof of the nasopharynx (4.16±1.92 and 6.65±2.81, respectively), with SUVs significantly differing between the two types of lesions (P<0.001). An associated increased (18)F-FDG uptake in Waldeyer's ring and the salivary glands occurred in benign but not in malignant lesions. The ratio of uptake in the midline roof of the nasopharynx and the palatine tonsil in the benign lesions (0.92±0.42) was significantly lower than that in the malignant lesions (1.76±0.93) (P<0.001). CONCLUSION: The analysis of the intensity and patterns of (18)F-FDG uptake in various regions of Waldeyer's ring provides a feasible modality for the differentiation between benign lesions and malignant nasopharyngeal midline roof lesions.

RNA silencing targeting PIN (protein inhibitor of neuronal nitric oxide synthase) attenuates the development of hypertension in young spontaneously hypertensive rats.

Nitric oxide (NO) deficiency contributes to hypertension. We previously showed that neuronal nitric oxide synthase (nNOS) was involved in hypertension and kidney damage in spontaneously hypertensive rats (SHRs). The protein inhibitor of nNOS (PIN) has been reported to inhibit activity of nNOS.Thus, we tested whether increased PIN in the kidney results in hypertension and whether small interfering RNA (siRNA) targeting PIN attenuates hypertension in SHRs. Four-week-old male SHRs were assigned into three groups (n = 6-7/group): SHR; SHR + PIN, SHR that received siRNA targeting PIN; and SHR + NC, SHR treated with random negative control siRNA. Rats were sacrificed at 12 weeks of age. PIN protein expression was inhibited considerably when PIN siRNA was transfected into NRK52E cells (90% siRNA at 1 nM). The increases of BP were attenuated by siRNA targeting PIN in 12-week-old SHRs. Immunostaining of nNOS-α and total nNOS was greater in SHR + PIN group than SHR. Moreover, renal superoxide production and 8-hydroxydeoxyguanosine (8-OHdG) staining were more decreased in the SHR + PIN group than SHRs. We conclude that PIN siRNA reduced PIN expression in vitro and in vivo. PIN siRNA therapy attenuates hypertension in SHRs at 12 weeks of age. Our results suggest that PIN is involved in the development of hypertension.

The significance of alteration 2-[fluorine-18]fluoro-2-deoxy-(D)-glucose uptake in the liver and skeletal muscles of patients with hyperthyroidism.

RATIONALE AND OBJECTIVES: Hyperthyroidism leads to an enhanced demand for glucose. The hypothesis of the study is that 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) can demonstrate the alteration of systemic glucose metabolism in hyperthyroidism patients by measuring the FDG standard uptake value (SUV) in liver and skeletal muscle. MATERIALS AND METHODS: Forty-eight active hyperthyroidism patients and 30 control participants were recruited for the study. The intensity of FDG uptake in the liver and thigh muscles was graded subjectively, comprising three groups: group I, higher FDG uptake in the liver; group II, equal FDG uptake in the liver and muscles; and group III, higher FDG uptake in the muscles. Ten subjects with FDG PET scans at hyperthyroid and euthyroid status were analyzed. Serum levels of thyroxine (T4) and triiodothyronine (T3) correlated to the SUVs of the liver and muscles. RESULTS: Forty-one patients (41/48, 85.4%) showed symmetrically increased FDG uptake in the muscles (22 in group I, 9 in group II, and 17 in group III). Group I patients were significantly older than group II (P = .02) and group III (P = .001) patients. The correlation coefficient between the serum T3, T4, and SUV levels in the muscles was significant (r = 0.47-0.77, P < .01), particularly in liver and muscle FDG uptake between hyperthyroid and euthyroid states. In the 30 control subjects, there was normal physiological FDG uptake in the liver and muscles. CONCLUSION: In PET scans showing a pattern of decreased liver and increased skeletal muscle FDG uptake in hyperthyroidism patients, this change of FDG distribution is correspondence to the severity of hyperthyroidism status.

Dislodgement of port-A catheters in pediatric oncology patients: 11 years of experience.

BACKGROUND: Port-A catheters are frequently used in pediatric cancer patients. Their dislodgement is potentially seriously risky although the incidence is not high. We analyzed our 11 years of data to address this important problem. METHODS: From January 2001 to December 2011, 330 port-A catheters of different brands were implanted in pediatric cancer patients. In total, eight children suffered a dislodgement of their catheter. Their ages ranged from four to thirteen years, with a median age of ten. Five patients presented with catheter dysfunction, two presented with a cough and one was identified incidentally during surgery to remove his port. RESULTS: The downstream ends of the dislodged catheters were located in the right atrium (three patients), left pulmonary artery (three) and inferior vena cava (two). Six of the eight catheters were broken at the site of anastomosis to the port and the other two were broken halfway in between. All episodes of dislodgement happened after the chemotherapy regimen was completed. The dislodged catheters were successfully retrieved without complications by transcatheter retrieval using a gooseneck snare. CONCLUSIONS: The dislodgment rate of port-A catheter in our series was 2.4%. Chest X-rays can rapidly detect the problem. Most of the catheters were broken at the site of anastomosis. Earlier explantation of port-A catheters after completing chemotherapy may be considered to avoid the dislodgement of catheters, but this needs to be weighed against the possibility of underlying disease recurrence. However, we should re-examine how long port-A catheters need to be retained after chemotherapy considering the improved cure rate of pediatric cancer.

The frequency and spectrum of thymus 2-[fluorine-18] fluoro-2-deoxy-D-glucose uptake patterns in hyperthyroidism patients.

RATIONALE AND OBJECTIVES: Thymic hyperplasia is associated with hyperthyroidism. Increased thymus 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) uptake in hyperthyroidism patients has been reported. The aim of this study was to analyze the FDG positron emission tomography (PET) thymus uptake spectrum in patients with active hyperthyroidism with correlation with serum hormones. MATERIALS AND METHODS: The prospective study included FDG PET scans from 65 hyperthyroidism patients and 30 subjects with euthyroid status as control group. The intensity of FDG uptake in thyroid and thymus regions was graded subjectively on a five-point scale and semi-quantitatively by measuring standard uptake value (SUV). Correlation coefficient between thymus SUV and serum thyroxine, triiodothyronine, thyrotropin, thyroid peroxidase antibodies (TPO Ab), thyrotropin receptor autoantibody (TR Ab), and thymulin were analyzed. RESULTS: Among 65 hyperthyroidism patients, 30 (46.2%) and 39 (60%) patients showed thyroid and thymus FDG uptake, respectively. The frequency of thymus uptake FDG was high in patients younger than age 40 (28/31, 90.3%). The patterns of the thymic FDG uptake include inverted V or triangular, separated triangular, united nontriangular, unilateral right or left extension, and focal midline. Focal midline FDG uptake was the most common pattern (15/39, 38.5%). None of the control group showed thymus FDG uptake. The correlation coefficient between the FDG uptake SUV levels in thymus and serum hormones, thyrotropin, TPO Ab, TR Ab, and thymulin levels were all low (P > .05). CONCLUSIONS: In FDG PET scan, thymus activity was common in hyperthyroidism patients; this should not be misdiagnosed as a malignancy in patients exhibiting weight loss.

Utility of 18F-FDG PET/CT uptake patterns in Waldeyer's ring for differentiating benign from malignant lesions in lateral pharyngeal recess of nasopharynx.

UNLABELLED: Focally increased (18)F-FDG uptake in the lateral pharyngeal recess (LPR) of the nasopharynx due to a benign or malignant lesion is not an uncommon finding on PET images. The aim of this study was to evaluate whether, on PET/CT images, (18)F-FDG uptake occurs with characteristic patterns and intensities in various regions of Waldeyer's ring that can improve our ability to differentiate benign from malignant lesions. METHODS: Data generated from the (18)F-FDG PET/CT images of 1,628 subjects in our cancer-screening program were analyzed. Increased uptake in the LPR was observed in 80 subjects (4.9%) presenting with benign lesions, including 53 subjects without and 27 subjects with symptoms of upper airway discomfort. In addition, 30 healthy controls and 21 patients with newly diagnosed nasopharyngeal carcinoma were recruited for this study. Visual uptake, measurements of the lesions' standardized uptake value (SUV), and any abnormalities on PET/CT were evaluated. The receiver-operating-characteristic curve and area under the curve were applied to evaluate the discriminating power. RESULTS: Increased (18)F-FDG uptake (SUV, mean +/- SD) was found in the LPR, with a statistically significant (P < 0.001) difference between benign lesions (3.0 +/- 1.16) and malignant lesions (7.03 +/- 3.83). However, associated increased uptake exclusively in the palatine tonsil, lingual tonsil, and submandibular gland was found in both asymptomatic and symptomatic subjects. The ratio of LPR uptake to palatine tonsil uptake (N/P ratio) in benign lesions (0.81 +/- 0.37) was significantly (P < 0.001) lower than that in malignant lesions (2.30 +/- 1.62). Higher incidences of asymmetric (18)F-FDG LPR uptake, cervical lymph node uptake, and asymmetric wall thickening of the LPR on CT were observed in patients with nasopharyngeal carcinoma. When an SUV of less than 3.9 and an N/P ratio of less than 1.5 were used as cutoff points in subjects showing the combination of symmetric uptake in the LPR and normal or symmetric wall thickening, and detectable lymph node uptake, the area under the curve for benign lesions on PET/CT was 0.932 +/- 0.042 (95% confidence interval, 0.86-0.98), with a sensitivity of 90.4% and a specificity of 93.8%. CONCLUSION: The intensity and patterns of (18)F-FDG uptake in various regions of Waldeyer's ring along with CT scan findings provide a feasible modality to differentiate benign from malignant nasopharyngeal lesions.

The effects of preventive intervention for betel nut chewing in school.

PURPOSE: This study was to explore the effect of preventive health education intervention in the knowledge, attitude, practice of betel nut chewing, and self-efficacy of anti-betel nut chewing for adolescent students. METHODS: One hundred eighty-six indigenous samples were recruited, and divided into experimental and control groups. The experimental group underwent fourteen-week classes regarding the prevention of betel nut chewing. Both groups took post-tests immediately after intervention in order to evaluate the instant effect of the teaching program. The follow-up (post-post-test) evaluated the instant improvement at the 28th week (14 weeks after the end of the class). RESULTS: There was no difference in knowledge of the hazards of betel nut chewing among pre-tests, post-tests, and post-post-test in the experimental group. The attitude, practice of betel nut chewing and self-efficacy of anti-betel nut chewing aspects was significantly different among pre-tests, post-tests, and post-post-test after intervention. There was a significantly immediate and instant improvement after health education intervention. CONCLUSION: Health education enables students to better resist the use of betel nuts. This study confirmed the importance of health education programs in dealing with the health risks of betel nut chewing for the risk group students.

Betel nut chewing: the prevalence and the intergenerational effect of parental behavior on adolescent students.

PURPOSE: To explore the betel nut chewing prevalence among students, analyze the probability and the odds ratio of ex-chewers and current chewers, as well as the correlation between parental behavior characteristics and those of adolescents chewing betel nut. METHODS: A cross-sectional survey was designed and 10,288 Taiwanese students answered the questionnaires in 2002. A structured questionnaire included information about betel nut chewing behavior among the adolescent students, sociodemographic data, and the betel nut chewing practice among parents or classmates. Samples were randomly chosen from each cluster of different types of schools in various areas. Three different grade levels of the first, second, and third grade (ages 16-18 years) were selected. Frequency distribution was used to analyze the prevalence among adolescent students, and Chi-square tests were used to compare the differences of betel nut chewing behavior among genders and the effect of parental behavior and socioeconomic factors. Logistic regression was used to analyze the odds ratio of the prevalence of adolescent students' betel nut chewing in the different types of schools and by gender. RESULTS: When the parents' marriage was not successful, or was of a lower social status, a higher incidence of adolescent betel nut chewing was observed. It was easy to experience betel nut chewing in adolescence if either parent chewed betel nut. The prevalence of betel nut chewing among male students was higher than female students and among vocational school students than general school students. The odds ratio of agricultural school students to general school students was highest of all the ex-chewers and current chewers from different types of schools. CONCLUSIONS: Betel nut chewing behavior is related to the effect of parental behavior on adolescent students. Apparently, it is indicated that there is a significant intergenerational effect of the parent's behavior on their children's behavior.

Betel nut chewing and related factors in adolescent students in Taiwan.

OBJECTIVE: To investigate the prevalence of betel nut chewing and related factors among adolescent students in general, manufacturing, commercial, agricultural and medical technology schools in Taiwan. To make suggestions regarding how health authorities can reduce the number of students taking up the habit. MATERIALS AND METHODS: A cross-sectional survey was designed, and 10,288 students answered the questionnaire. RESULTS: Significantly more male than female students were betel nut chewers. The less urbanized areas were also associated with a higher prevalence of the habit. The prevalence of the habit grew with increasing age. By analysing betel nut chewing behaviour, it was found that most students started chewing betel nuts because of curiosity, and most obtained betel nuts from their friends and classmates. Betel nut chewing behaviour is definitely related to peer pressure. Most betel nut chewers did not realize that withdrawal could lead to physiological reactions, and they were ignorant of any risk to health even though they were compulsive betel nut chewers. The health-harming behaviours of both smoking and drinking were found in many betel nut chewers, particularly smoking. CONCLUSION: This study confirmed the need for a health education programme dealing with the health risks of betel nut chewing for students at risk. The health authorities could also develop a programme for betel nut chewing among Taiwan's adolescent students, emphasizing the dangers of this habit.

Measuring the efficiency of dental departments in medical centers: a nonparametric analysis approach.

Data envelopment analysis (DEA), a cross-sectional study design based on secondary data analysis, was used to evaluate the relative operational efficiency of 16 dental departments in medical centers in Taiwan in 1999. The results indicated that 68.7% of all dental departments in medical centers had poor performance in terms of overall efficiency and scale efficiency. All relatively efficient dental departments were in private medical centers. Half of these dental departments were unable to fully utilize available medical resources. 75.0% of public medical centers did not take full advantage of medical resources at their disposal. In the returns to scale, 56.3% of dental departments in medical centers exhibited increasing returns to scale, due to the insufficient scale influencing overall hospital operational efficiency. Public medical centers accounted for 77.8% of the institutions affected. The scale of dental departments in private medical centers was more appropriate than those in public medical centers. In the sensitivity analysis, the numbers of residents, interns, and published papers were used to assess teaching and research. Greater emphasis on teaching and research in medical centers has a large effect on the relative inefficiency of hospital operation. Dental departments in private medical centers had a higher mean overall efficiency score than those in public medical centers, and the overall efficiency of dental departments in non-university hospitals was greater than those in university hospitals. There was no information to evaluate the long-term efficiency of each dental department in all hospitals. A different combination of input and output variables, using common multipliers for efficiency value measurements in DEA, may help establish different pioneering dental departments in hospitals.