Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2 deletion female mice.

Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, we and others demonstrated that visual sensory stimulation using rhythmic 40 Hz light flicker effectively improved cognitive deficits in mouse models of Alzheimer's disease and stroke. However, whether rhythmic visual 40 Hz light flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2 deletion female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz light stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2 deletion female mice was also effectively reduced by 40 Hz light treatment. Importantly, the 40 Hz light flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz light flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2 deletion female mice. Elevated adenosine functioned through its cognate A1 receptor (A1R) to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A1R using a specific antagonist DPCPX or knocking down the A1R in the PFC using a shRNA completely ablated the beneficial effects of 40 Hz light flicker. Thus, this study identified adenosine as a novel neurochemical mediator for ameliorating social novelty deficit by reducing excitatory neurotransmission during 40 Hz light flicker treatment. The 40 Hz light stimulation warrants further development as a non-invasive ASD therapeutics.

Risk factors for acute complicated appendicitis in children aged three years and younger.

OBJECTIVE: The aim of this study is to identify risk factors associated with acute complicated appendicitis (CA) in children aged three years or younger, providing a theoretical foundation for the management and treatment of acute appendicitis (AA). METHODS: A retrospective analysis was conducted on 135 pediatric patients with AA, admitted to the Department of General Surgery at Anhui Children's Hospital between December 2020 and December 2023, who underwent successful surgical treatment. Based on the intraoperative and postoperative pathological findings, patients were categorized into two groups: complicated appendicitis (CA) (n = 97 cases) and uncomplicated appendicitis (UA) (n = 38 cases). Clinical data including gender, age, weight, disease duration, preoperative white blood cell count (WCC), neutrophil granulocyte (NEUT) count, C-reactive protein (CRP) levels, total bilirubin (TBil) levels, procalcitonin (PCT) levels, calprotectin (Cal) levels, preoperative ultrasound results indicating the presence or absence of fecaliths, maximum appendix diameter, and pediatric appendicitis sore (PAS) were collected and analyzed. Comparative analysis was performed to investigate the differences between the groups and identify risk factors of CA. RESULTS: The CA group exhibited significantly higher values in disease duration, CRP levels, PCT, Cal, presence of appendiceal fecaliths, maximum appendix diameter, and PAS compared to the UA group (P < 0.05). Multivariate analysis identified CRP levels, maximum appendix diameter, and PAS as independent risk factors for CA. Specifically, differences in CRP level (OR = 1.045, 95% CI:1.024 ~ 1.067, P < 0.001), PAS (OR = 1.768, 95% CI:1.086 ~ 2.879, P = 0.022), and maximum appendix diameter (OR = 1.860, 95% CI:1.085 ~ 3.191, P = 0.024) were significant. The area under the receiver operating characteristic curve values were 0.6776 for the PAS, 0.7663 for CRP, and 0.5604 for the maximum appendix diameter. CONCLUSION: CRP levels, PAS, and maximum appendix diameter are independent risk factors for CA in children under three years of age. These parameters are valuable for the early diagnosis of CA.

[Effects of antenatal corticosteroid therapy in pregnant women on the brain development of preterm infants as assessed by amplitude-integrated electroencephalography]. / æŒ¯å¹ æ•´åˆè„‘ç”µå›¾è¯„ä¼°å­•å¦‡äº§å‰ç³–çš®è´¨æ¿€ç´ æ²»ç–—å¯¹æ—©äº§å„¿è„‘å‘è‚²çš„å½±å“.

OBJECTIVES: To investigate the effects of antenatal corticosteroid (ACS) therapy in pregnant women on the brain development of preterm infants using amplitude-integrated electroencephalography (aEEG). METHODS: A retrospective analysis was conducted on 211 preterm infants with a gestational age of 28 to 34+6 weeks. The infants were divided into an ACS group (131 cases) and a control group (80 cases) based on whether antenatal dexamethasone was given for promoting fetal lung maturity. The first aEEG monitoring (referred to as aEEG1) was performed within 24 hours after birth, and the second aEEG monitoring (referred to as aEEG2) was performed between 5 to 7 days after birth. The aEEG results were compared between the two groups. RESULTS: In preterm infants with a gestational age of 28 to 31+6 weeks, the ACS group showed a more mature periodic pattern and higher lower amplitude boundary in aEEG1 compared to the control group (P<0.05). In preterm infants with a gestational age of 32 to 33+6 weeks and 34 to 34+6 weeks, the ACS group showed a higher proportion of continuous patterns, more mature periodic patterns and higher Burdjalov scores in aEEG1 (P<0.05). And the ACS group exhibited a higher proportion of continuous patterns, more mature periodic patterns, higher lower amplitude boundaries, narrower bandwidths, and higher Burdjalov scores in aEEG2 (P<0.05). CONCLUSIONS: ACS-treated preterm infants have more mature aEEG patterns compared to those not treated with ACS, suggesting a beneficial effect of ACS on the brain development of preterm infants.

Elimination of perineuronal nets in CA1 disrupts GABA release and long-term contextual fear memory retention.

Perineuronal nets (PNNs) which mostly surround the parvalbumin (PV) neurons, have been shown to play critical roles in neural plasticity. Recently, PNNs have been shown to regulate fear-associated memory, but the molecular mechanism is still unclear. In this study, we found that removal of PNNs in vivo using chondroitinase ABC (ChABC) injection resulted in reduced firing rate of PV neurons and decreased inhibitory synaptic transmission in both PV neurons and excitatory neurons in the CA1 hippocampus. Interestingly, altered synaptic transmission appears to be mediated by presynaptic changes. Furthermore, ChABC treatment disrupts long-term contextual fear memory retention. These results suggest PNNs might alter fear memory by reducing the presynaptic GABA release.

Distinctive effects of NMDA receptor modulators on cerebral microcirculation in a schizophrenia mouse model.

Substantial evidence demonstrates that schizophrenia patients have altered cerebral microcirculation. However, little is known regarding how cerebral microcirculatory blood flow (microCBF) changes in schizophrenia. Here, using time-lapse two-photon imaging of individual capillaries, we demonstrated a substantial decrease in cerebral microcirculation in a mouse model of schizophrenia. The involvement of NMDA receptor (NMDAR) functions was investigated to understand further the mechanism of microcirculation reduction in this animal model. Administration of D-serine, a selective full agonist at the glycine site of NMDAR, significantly increased the microCBF in the schizophrenia mouse. Interestingly, administration of GNE-8324, a GluN2A-selective positive allosteric modulator that selectively enhances NMDAR-mediated synaptic responses in inhibitory but not excitatory neurons, had no effect on the microCBF of the schizophrenia mice. Together, these data indicated that NMDAR participated in the regulation of microcirculation in schizophrenia using a mechanism dependent on the tonic NMDAR signaling and the selective modulation of inhibitory neuron activity. Further studies are warranted to establish NMDAR's role in modulating microcirculation in schizophrenia.

Potential clinical biomarkers in monitoring the severity of Hantaan virus infection.

Hantavirus, which causes hemorrhagic fever with renal syndrome (HFRS) is almost prevalent worldwide. While Hantaan virus (HTNV) causes the most severe form of HFRS with typical clinical manifestations of thrombocytopenia, increased vascular permeability, and acute kidney injury. Although the knowledge of the pathogenesis of HFRS is still limited, immune dysfunction and pathological damage caused by disorders of immune regulation are proposed to play a vital role in the development of the disorder, and the endothelium is considered to be the primary target of hantaviruses. Here, we reviewed the production and function of multiple molecules, mainly focusing on their role in immune response, endothelium, vascular permeability regulation, and platelet and coagulation activation which are closely related to the pathogenesis of HTNV infection. meanwhile, the relationship between these molecules and characteristics of HTNV infection including the hospital duration, immune dysfunction, thrombocytopenia, leukocytosis, and acute kidney injury are also presented, to provide a novel insight into the potential role of these molecules as monitoring markers for HTNV infection.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

Omics Analysis Unveils the Pathway Involved in the Anthocyanin Biosynthesis in Tomato Seedling and Fruits.

The purple tomato variety 'Indigo Rose' (InR) is favored due to its bright appearance, abundant anthocyanins and outstanding antioxidant capacity. SlHY5 is associated with anthocyanin biosynthesis in 'Indigo Rose' plants. However, residual anthocyanins still present in Slhy5 seedlings and fruit peel indicated there was an anthocyanin induction pathway that is independent of HY5 in plants. The molecular mechanism of anthocyanins formation in 'Indigo Rose' and Slhy5 mutants is unclear. In this study, we performed omics analysis to clarify the regulatory network underlying anthocyanin biosynthesis in seedling and fruit peel of 'Indigo Rose' and Slhy5 mutant. Results showed that the total amount of anthocyanins in both seedling and fruit of InR was significantly higher than those in the Slhy5 mutant, and most genes associated with anthocyanin biosynthesis exhibited higher expression levels in InR, suggesting that SlHY5 play pivotal roles in flavonoid biosynthesis both in tomato seedlings and fruit. Yeast two-hybrid (Y2H) results revealed that SlBBX24 physically interacts with SlAN2-like and SlAN2, while SlWRKY44 could interact with SlAN11 protein. Unexpectedly, both SlPIF1 and SlPIF3 were found to interact with SlBBX24, SlAN1 and SlJAF13 by yeast two-hybrid assay. Suppression of SlBBX24 by virus-induced gene silencing (VIGS) retarded the purple coloration of the fruit peel, indicating an important role of SlBBX24 in the regulation of anthocyanin accumulation. These results deepen the understanding of purple color formation in tomato seedlings and fruits in an HY5-dependent or independent manner via excavating the genes involved in anthocyanin biosynthesis based on omics analysis.

Elevated activity in the dorsal dentate gyrus reduces expression of fear memory after fear extinction training.

Background: Effectively reducing the expression of certain aversive memories (fear or trauma memories) with extinction training is generally viewed to be therapeutically important. A deeper understanding of the biological basis for a more effective extinction process is also of high scientific importance. Methods: Our study involved intraventricular injection or local injection into the dorsal dentate gyrus of anti-neuregulin 1 antibodies (anti-NRG1) before fear extinction training, followed by testing the expression of fear memory 24 hours afterward or 9 days later. We used local injection of chemogenetic or optogenetic viruses into the dorsal dentate gyrus to manipulate the activity of the dorsal dentate gyrus and test the expression of fear memory. We also examined the effect of deep brain stimulation in the dorsal dentate gyrus on the expression of fear memory. Results: Mice that received intraventricular injection with anti-NRG1 antibodies exhibited lower expression of fear memory and increased density of activated excitatory neurons in the dorsal dentate gyrus. Injection of anti-NRG1 antibodies directly into the dorsal dentate gyrus also led to lower expression of fear memory and more activated neurons in the dorsal dentate gyrus. Inhibiting the activity of dorsal dentate gyrus excitatory neurons using an inhibitory designer receptor exclusively activated by designer drugs (DREADD) eliminated the effects of the anti-NRG1 antibodies. Enhancing the activity of the dorsal dentate gyrus with an excitatory DREADD or optogenetic stimulation resulted in lower expression of fear memory in mice that did not receive infusion of anti-NRG1 antibodies. Deep brain stimulation in the dorsal dentate gyrus effectively suppressed expression of fear memory, both during and after fear extinction training. Limitations: The mechanism for the contribution of the dorsal dentate gyrus to the expression of fear memory needs further exploration. Conclusion: Activation of the dorsal dentate gyrus may play an important role in modulating the expression of fear memory; its potential use in fear memory extinction is worthy of further exploration.

The impact of D-cycloserine and sarcosine on in vivo frontal neural activity in a schizophrenia-like model.

BACKGROUND: N-methyl-D-aspartate receptor (NMDAR) hypofunction has been proposed to underlie the pathogenesis of schizophrenia. Specifically, reduced function of NMDARs leads to altered balance between excitation and inhibition which further drives neural network malfunctions. Clinical studies suggested that NMDAR modulators (glycine, D-serine, D-cycloserine and glycine transporter inhibitors) may be beneficial in treating schizophrenia patients. Preclinical evidence also suggested that these NMDAR modulators may enhance synaptic NMDAR function and synaptic plasticity in brain slices. However, an important issue that has not been addressed is whether these NMDAR modulators modulate neural activity/spiking in vivo. METHODS: By using in vivo calcium imaging and single unit recording, we tested the effect of D-cycloserine, sarcosine (glycine transporter 1 inhibitor) and glycine, on schizophrenia-like model mice. RESULTS: In vivo neural activity is significantly higher in the schizophrenia-like model mice, compared to control mice. D-cycloserine and sarcosine showed no significant effect on neural activity in the schizophrenia-like model mice. Glycine induced a large reduction in movement in home cage and reduced in vivo brain activity in control mice which prevented further analysis of its effect in schizophrenia-like model mice. CONCLUSIONS: We conclude that there is no significant impact of the tested NMDAR modulators on neural spiking in the schizophrenia-like model mice.

Codability of industry and occupation information from cancer registry records: Differences by patient demographics, casefinding source, payor, and cancer type.

INTRODUCTION: Industry and occupation (I&O) information collected by cancer registries is useful for assessing associations among jobs and malignancies. However, systematic differences in I&O availability can bias findings. METHODS: Codability by patient demographics, payor, identifying (casefinding) source, and cancer site was assessed using I&O text from first primaries diagnosed 2011-2012 and reported to California Cancer Registry. I&O were coded to a U.S. Census code or classified as blank/inadequate/unknown, retired, or not working for pay. RESULTS: Industry was codable for 37% of cases; 50% had "unknown" and 9% "retired" instead of usual industry. Cases initially reported by hospitals, covered by preferred providers, or with known occupational etiology had highest codable industry; cases from private pathology laboratories, with Medicaid, or diagnosed in outpatient settings had least. Occupation results were similar. CONCLUSIONS: Recording usual I&O for retirees and improving linkages for reporting entities without patient access would improve I&O codability and research validity.

The Neuropilins and Their Ligands in Hematogenous Metastasis of Salivary Adenoid Cystic Carcinoma-An Immunohistochemical Study.

PURPOSE: We investigated the expression of neuropilin-1 (NRP1), neuropilin-2 (NRP2), vascular endothelial growth factor-A (VEGF-A), semaphorin-3A (Sema-3A), and semaphorin-3F (Sema-3F) in normal salivary gland (NSG) tissue, nonmetastatic salivary adenoid cystic carcinoma (SACC), and metastatic SACC to better understand their role in intratumoral angiogenesis and hematogenous metastasis of SACC. PATIENTS AND METHODS: The study included 60 SACC patients, equally divided between nonmetastatic SACC and metastatic SACC. We used 30 NSG samples as the control. The expression of cytokines was studied by immunohistochemistry and compared using the integrated optical density. The relationship between NRP1, NRP2, VEGF-A, and Sema-3A expression and microvessel density (MVD) was analyzed in the 3 groups. RESULTS: In metastatic SACC, the expression levels of NRP1 and VEGF-A were significantly greater than those in nonmetastatic SACC and NSG. The expression of Sema-3A and Sema-3F was significantly lower in metastatic SACC than that in nonmetastatic SACC and NSG (P < .0001). No significant differences were found in NRP2 expression among the 3 groups (P = .43). The MVD of metastatic SACC was significantly greater than that of nonmetastatic SACC and NSG (P < .0001). However, the lymphatic vessel density of the 3 groups was not significantly different statistically. The relationship between MVD and NRP1 or VEGF-A showed a significant positive correlation (P < .0001, for both). However, a significant negative correlation was found between the MVD and Sema-3A or Sema-3F expression (P < .0001, for both). CONCLUSIONS: Hematogenous metastasis of SACC is correlated with high expression of NRP1 and VEGF-A and low expression of Sema-3A and Sema-3F. The increased numbers of microvessels induced by VEGF-A signaling, combined with NRP1, could be one of the key reasons leading to the enhanced hematogenous metastasis in SACC.

High Expression of Prospero-Related Homeobox-1 (PROX1) Is Associated With Poor Prognosis in Patients With Salivary Adenoid Cystic Carcinoma.

PURPOSE: Prospero-related homeobox-1 (PROX1) plays an important role in the invasion and metastasis of many human cancers. However, the expression pattern of PROX1 in salivary adenoid cystic carcinoma (SACC) remains unclear. The aim of this study was to investigate PROX1 expression and its prognostic value in SACC. MATERIALS AND METHODS: PROX1 expression was determined by immunohistochemistry (IHC) in SACC tissue specimens. Correlations between PROX1 expression and clinicopathologic features were investigated. The Kaplan-Meier method was used to analyze the correlation between PROX1 expression and survival. Independent prognostic factors associated with overall survival (OS) were analyzed using Cox regression analysis. RESULTS: The IHC data showed that the PROX1 positivity rate in SACC tissue specimens was significantly higher than that in normal salivary gland tissues (71.1 vs 13.3%; P < .05). PROX1 expression was detected mainly in the nucleolus. In addition, PROX1 expression was correlated with perineural invasion, local regional recurrence, and distant metastasis of patients with SACC (P < .05), and no significant association was found between PROX1 expression and other clinicopathologic parameters. Data indicated that patients with positive PROX1 expression had poor OS compared with those with negative PROX1 expression (P = .0005). Multivariate analysis showed that PROX1 expression, local regional recurrence, and distant metastasis were independent prognostic factors for OS. CONCLUSIONS: These findings showed that PROX1 expression was statistically higher in SACC specimens. Positive expression of PROX1 might serve as a potential predictor of prognosis in SACC.

[Regulation of γ-globin gene expression and its clinical applications].

Human hemoglobin, a tetramer containing two α globins and two ß globins, is responsible for oxygen transportation in the body. Globin genes are clustered in the genome and their expressions are regulated by a variety of cis-acting elements and trans-acting factors, exhibiting a developmental- and tissue-specific manner. ß-thalassemia and sickle cell diseases are two of the most common autosomal recessive disorders caused by mutations in the ß-globin gene. Besides α- and ß-globins, the human genome also has a third globin gene-γ-globin. Like ß-globin, γ-globin also has oxygen-carrying capabilities. Unlike ß-globin, γ-globin is mainly expressed at the fetal stage and remains intact in ß-thalassemia and sickle cell disease patients. Thus, reactivating the expression of the γ-globin gene in adult patients to ameliorate their clinical symptoms has become one of the best therapeutic strategies to treat ß-thalassemia and sickle cell diseases. Some drugs have been developed clinically to increase γ-globin gene expression for those patients. With the development of genome editing technologies, precision gene therapy for these diseases is underway. This review focuses on the main transcription factors and epigenetic modifiers that are involved in γ-globin gene regulation, and some applications for clinical treatment for ß-thalassemia and sickle cell diseases based on these studies. We hope to provide a useful reference for in-depth studies on transcriptional regulation of γ-globin gene expression in the future.

Mortality from Amyotrophic Lateral Sclerosis and Parkinson's Disease Among Different Occupation Groups - United States, 1985-2011.

Amyotrophic lateral sclerosis (ALS) and Parkinson's disease, both progressive neurodegenerative diseases, affect >1 million Americans (1,2). Consistently reported risk factors for ALS include increasing age, male sex, and cigarette smoking (1); risk factors for Parkinson's disease include increasing age, male sex, and pesticide exposure, whereas cigarette smoking and caffeine consumption are inversely associated (2). Relative to cancer or respiratory diseases, the role of occupation in neurologic diseases is much less studied and less well understood (3). CDC evaluated associations between usual occupation and ALS and Parkinson's disease mortality using data from CDC's National Institute for Occupational Safety and Health (NIOSH) National Occupational Mortality Surveillance (NOMS), a population-based surveillance system that includes approximately 12.1 million deaths from 30 U.S. states.* Associations were estimated using proportionate mortality ratios (PMRs), standardizing indirectly by age, sex, race, and calendar year to the standard population of all NOMS deaths with occupation information. Occupations associated with higher socioeconomic status (SES) had elevated ALS and Parkinson's disease mortality. The shifts in the U.S. workforce toward older ages and higher SES occupations† highlight the importance of understanding this finding, which will require studies with designs that provide evidence for causality, detailed exposure assessment, and adjustment for additional potential confounders.

Effect of E-waste Recycling on Urinary Metabolites of Organophosphate Flame Retardants and Plasticizers and Their Association with Oxidative Stress.

In this study, three chlorinated (Cl-mOPs) and five nonchlorinated (NCl-mOPs) organophosphate metabolites were determined in urine samples collected from participants living in an electronic waste (e-waste) dismantling area (n = 175) and two reference areas (rural, n = 29 and urban, n = 17) in southern China. Bis(2-chloroethyl) phosphate [BCEP, geometric mean (GM): 0.72 ng/mL] was the most abundant Cl-mOP, and diphenyl phosphate (DPHP, 0.55 ng/mL) was the most abundant NCl-mOP. The GM concentrations of mOPs in the e-waste dismantling sites were higher than those in the rural control site. These differences were significant for BCEP (p < 0.05) and DPHP (p < 0.01). Results suggested that e-waste dismantling activities contributed to human exposure to OPs. In the e-waste sites, the urinary concentrations of bis(2-chloro-isopropyl) phosphate (r = 0.484, p < 0.01), BCEP (r = 0.504, p < 0.01), dibutyl phosphate (r = 0.214, p < 0.05), and DPHP (r = 0.440, p < 0.01) were significantly increased as the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative stress, increased. Our results also suggested that human exposure to OPs might be correlated with DNA oxidative stress for residents in e-waste dismantling areas. To our knowledge, this study is the first to report the urinary levels of mOPs in China and examine the association between OP exposure and 8-OHdG in humans.

Levetiracetam: Probably Associated Diurnal Frequent Urination.

Diurnal frequent urination is a common condition in elementary school children who are especially at risk for associated somatic and behavioral problems. Levetiracetam (LEV) is a broad-spectrum antiepileptic drug that has been used in both partial and generalized seizures and less commonly adverse effects including psychiatric and behavioral problems. Diurnal frequent urination is not a well-known adverse effect of LEV. Here, we reported 2 pediatric cases with epilepsy that developed diurnal frequent urination after LEV administration. Case 1 was a 6-year-old male patient who presented urinary frequency and urgency in the daytime since the third day after LEV was given as adjunctive therapy. Symptoms increased accompanied by the raised dosage of LEV. Laboratory tests and auxiliary examinations did not found evidence of organic disease. Diurnal frequent urination due to LEV was suspected, and then the drug was discontinued. As expected, his frequency of urination returned to normal levels. Another 13-year-old female patient got similar clinical manifestations after oral LEV monotherapy and the symptoms became aggravated while in stress state. Since the most common causes of frequent micturition had been ruled out, the patient was considered to be diagnosed with LEV-associated psychogenic frequent urination. The dosage of LEV was reduced to one-third, and the frequency of urination was reduced by 60%. Both patients got the Naranjo score of 6, which indicated that LEV was a "probable" cause of diurnal frequent urination. Although a definite causal link between LEV and diurnal urinary frequency in the 2 cases remains to be established, we argue that diurnal frequent urination associated with LEV deserves clinician's attention.

Overview of the National Occupational Mortality Surveillance (NOMS) system: leukemia and acute myocardial infarction risk by industry and occupation in 30 US states 1985-1999, 2003-2004, and 2007.

BACKGROUND: Cancer and chronic disease are leading causes of death in the US with an estimated cost of $46 billion. METHODS: We analyzed 11 million cause-specific deaths of US workers age 18-64 years in 30 states during 1985-1999, 2003-2004, and 2007 by occupation, industry, race, gender, and Hispanic origin. RESULTS: The highest significantly elevated proportionate leukemia mortality was observed in engineers, protective service, and advertising sales manager occupations and in banks/savings &loans/credit agencies, public safety, and public administration industries. The highest significantly elevated smoking-adjusted acute myocardial infarction mortality was noted in industrial and refractory machinery mechanics, farmers, mining machine operators, and agricultural worker occupations; and wholesale farm supplies, agricultural chemical, synthetic rubber, and agricultural crop industries. CONCLUSIONS: Significantly elevated risks for acute myocardial infarction and leukemia were observed across several occupations and industries that confirm existing reports and add new information. Interested investigators can access the NOMS website at http://www.cdc.gov/niosh/topics/NOMS/.