Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner

Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, residente-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10 mg/kg suppressed all behaviors, which was accompanied by increased dopamine and serotonin levels in the medial prefrontal cortex (mPFC) but not in the nucleus accumbens (NAc). Although the most effective dose for depressive-like behavior was 30 mg/kg, the highest dose increased aggressive behavior and unaffected impulsive behavior. Increased dopamine levels in the NAc could be responsible for the effects. In addition, the mice basal impulsivity was negatively correlated with the latency to the first agonistic behavior. Thus, the optimal dose range of milnacipran is narrower than previously thought. Finding drugs that increase serotonin and dopamine levels in the mPFC without affecting dopamine levels in the NAc is a potential strategy for developing novel antidepressants

Chronic pelvic pain due to pelvic lymphangioleiomyomatosis: A case report

AbstractLymphangioleiomyomatosis (LAM), a rare multisystem disease affecting mainly young women, is characterized by an abnormal proliferation of smooth muscle-like cells in the lungs. We report a case of endometriosis with chronic pelvic pain due to pelvic LAM. A 41-year-old gravida 1, para 1 woman had been experiencing intermittent left pelvic pain for several years. She also complained of dyspnea on effort 2 years previously, and was diagnosed with pulmonary LAM. Abdominal magnetic resonance imaging showed a right ovarian endometriotic cyst and a left pelvic mass. She was referred to our hospital for the treatment of pelvic pain; she underwent laparoscopic cystectomy of the right ovarian endometriotic cyst. Her left pelvic cyst was found in the retroperitoneal space, and biopsy confirmed the diagnosis of LAM. Therefore, we suggest that LAM localized in the pelvis should be considered when a patient with pulmonary LAM presents with pelvic pain or abdominal distention

Application of CO-oximeter for Forensic Samples

CO-oximeter is routinely used in clinical practice, and it has been applied in the field of forensic medicine. It is a simultaneous and nondestructive technique for the analysis of total hemoglobin (Hb) and various Hb species, such as oxyhemoglobin, reduced hemoglobin, carboxyhemoglobin, and methemoglobin. It automatically measures the proportion of each species of Hb and oxygen contents. This is an easy, rapid, and convenient way as the laboratory test. Since there are many advantages such as no necessity of sample preparation, easy handling, and portability, it may provide valuable information for forensic diagnosis. In the present paper, we discuss about the diagnostic application of CO-oximeter in the field of forensic medicine

Simplified Analysis of Toxic Gaseous Substance in Forensic Practice: Experiences from Japan

Toxicological examination in forensic practice is important for the proper diagnosis of acute poisoning. We have discussed the properties and features of poisoning incidents due to gaseous substances and elaborated on the simplified analytical techniques and apparatus used for their identification and quantitation for forensic purposes. Briefly, we have explained the simplified analysis of toxic gaseous substances such as carbon monoxide, hydrogen cyanide, hydrogen sulfide, and helium in blood. The techniques used include color testing, gas chromatography, detector tube, oximeter, and spectrophotometric method. In doing so, we have shared our experiences and highlighted the fact that the analysis of gaseous substances can be performed using readily available laboratory tools and equipment. We have emphasized the need and usefulness of the reference data tables for guiding forensic diagnosis. We hope that the above overview will assist other colleagues to implement such simplified techniques for the advancement of forensic medicine practice

Nuclear dynamics of topoisomerase II beta reflects its catalytic activity that is regulated by binding of RNA to the C-terminal domain

DNA topoisomerase II (topo II) changes DNA topology by cleavage/re-ligation cycle(s) and thus contributes to various nuclear DNA transactions. It is largely unknown how the enzyme is controlled in a nuclear context. Several studies have suggested that its C-terminal domain (CTD), which is dispensable for basal relaxation activity, has some regulatory influence. In this work, we examined the impact of nuclear localization on regulation of activity in nuclei. Specifically, human cells were transfected with wild-type and mutant topo II beta tagged with EGFP. Activity attenuation experiments and nuclear localization data reveal that the endogenous activity of topo II beta is correlated with its subnuclear distribution. The enzyme shuttles between an active form in the nucleoplasm and a quiescent form in the nucleolus in a dynamic equilibrium. Mechanistically, the process involves a tethering event with RNA. Isolated RNA inhibits the catalytic activity of topo II beta in vitro through the interaction with a specific 50-residue region of the CTD (termed the CRD). Taken together, these results suggest that both the subnuclear distribution and activity regulation of topo II beta are mediated by the interplay between cellular RNA and the CRD

Behavioural and physiological correlates of impulsivity in the domestic dog (Canis familiaris)

Impulsivity is a trait related to inhibitory control which is expressed in a range of behaviours. Impulsive individuals show a decreased ability to tolerate delay of reinforcement, and more impulsive behaviour has been linked to decreased levels of serotonin and dopamine in a number of species. In domestic dogs, impulsivity is implicated in problem behaviours that result from a lack of self control, but currently there are no published studies that assess behavioural and physiological measures of impulsivity in relation to this trait. Impulsivity scores were calculated for 41 dogs using an owner-report assessment, the Dog Impulsivity Assessment Scale (DIAS). Twenty-three of these subjects completed an operant choice task based on a delayed reward paradigm, to assess their tolerance to delay of reinforcement. High Pressure Liquid Chromatography (HPLC) with Fluorometric Detection was used to detect levels of the metabolites of serotonin (5-HIAA) and dopamine (HVA) in the urine of 17 of the subjects. Higher impulsivity scores were found to be significantly correlated with more impulsive behaviour (reduced tolerance to delay of reinforcement) in the behaviour tests and lower levels of urinary 5-HIAA and 5-HIAA/HVA ratio. The results demonstrate convergent validity between impulsivity (as assessed by the DIAS) and behavioural and physiological parameters

Case report: Fatal poisoning caused by additive effects of two barbiturates

A case of fatal poisoning involving multiple psychotropic drugs is presented. Quantitative toxicological analysis showed femoral blood concentrations of pentobarbital, phenobarbital, duloxetine, acetaminophen and tramadol were 10.39, 22.57, 0.22, 0.61 and 0.22 μg/ml, respectively. We concluded that the death was due to the additive effects of two barbiturates. As both pentobarbital and phenobarbital act on gamma-aminobutyric acid (GABA) receptors, central nervous system activity was suppressed, causing respiratory depression. Additive pharmacological effects should be considered in cases of massive ingestion of multiple drugs

Hand-carried ultrasound performed at bedside in cardiology inpatient setting – a comparative study with comprehensive echocardiography

BACKGROUND: Hand-carried ultrasound (HCU) devices have been demonstrated to improve the diagnosis of cardiac diseases over physical examination, and have the potential to broaden the versatility in ultrasound application. The role of these devices in the assessment of hospitalized patients is not completely established. In this study we sought to perform a direct comparison between bedside evaluation using HCU and comprehensive echocardiography (CE), in cardiology inpatient setting. METHODS: We studied 44 consecutive patients (mean age 54 ± 18 years, 25 men) who underwent bedside echocardiography using HCU and CE. HCU was performed by a cardiologist with level-2 training in the performance and interpretation of echocardiography, using two-dimensional imaging, color Doppler, and simple calliper measurements. CE was performed by an experienced echocardiographer (level-3 training) and considered as the gold standard. RESULTS: There were no significant differences in cardiac chamber dimensions and left ventricular ejection fraction determined by the two techniques. The agreement between HCU and CE for the detection of segmental wall motion abnormalities was 83% (Kappa = 0.58). There was good agreement for detecting significant mitral valve regurgitation (Kappa = 0.85), aortic regurgitation (kappa = 0.89), and tricuspid regurgitation (Kappa = 0.74). A complete evaluation of patients with stenotic and prosthetic dysfunctional valves, as well as pulmonary hypertension, was not possible using HCU due to its technical limitations in determining hemodynamic parameters. CONCLUSION: Bedside evaluation using HCU is helpful for assessing cardiac chamber dimensions, left ventricular global and segmental function, and significant valvular regurgitation. However, it has limitations regarding hemodynamic assessment, an important issue in the cardiology inpatient setting

カンゴショク ノ ダイガクイン シンガク ニ カンスル カンゴカンリシャ ノ ニンシキ : -シガケンナイ ノ カンゴカンリシャ ヲ タイショウ トシテ -

背景 近年, 看護系大学院の増加に伴い社会人大学院生が増加している. しかし, 職場の理解が得られず, キャリアを中断して学業に専念する学生や進学そのものを断念する者も多い. 目的 本学が大学院を開設する場合には, 他大学と同様に社会人が入学生の多くを占めると推測されるため, 看護職の大学院進学に関する看護管理者の認識について調査を行なった. 方法 滋賀県内の病院及び実習関連施設等の管理者144名を対象に質問紙調査を実施した. 結果 70名からの回答 (回収率48.61%) が得られた. 大学院修了看護職に期待する管理者は51.42%, 所属施設に大学院卒看護職が必要とする管理者は38.57%であったが, 両者ともわからないと回答した管理者は42.85%であった. また, 進学制度がある施設は25.71%であった. 結論 本調査対象である看護管理者が大学院修了看護職に期待する内容, 必要とする理由は, 研究や教育, 管理的役割, 看護実践の質的向上など先行研究と同様の結果であったが, 大学院修了看護職にどのように活動してもらうかイメージをもてていない管理者も多いことが明らかになった.Background Recently, the number of the graduate students of nursing who also work for full time jobs has been increasing as many new graduate schools of nursing have been established. However, many of them have been had to give up pursuing either their career or education, due to the lack of the understanding from their work places.Object When establishing a graduate school of nursing in our university, it is expected that many of the students will be working full time as it is seen in many other schools. Thus, we conducted a survey to the administrators of nursing institutions asking about their opinions for their workers to go on to graduate school education.Method Surveyed on 144 administrators of nursing institutions in Shiga prefecture, including the hospitals and institutions where our students train in, through questionnaires.Result 70 cases were collected (response rate: 48.61%). 51.42% have positive opinions forward the workers who have finished the master\u27s course of the field, 38.57% said they need them at their work places, and 42.85% said they do not know. However, only 25.71% of the institutions provided the system of supporting the workers for their further education and their main concern seems to be how the organizations and the workers can make mutual understanding for their career.Conclusion The survey showed that some of the administrators have positive opinions toward the workers who have finished the master\u27s degree course of nursing and that they feel the need for them at their work places as it was shown in previous studies. However, it has also been found that many of them do not have a clear picture of how those workers can be actively participated at their work places