Adverse Behavioral Effects Research Articles

The neural underpinnings of facial emotion recognition in ischemic stroke patients.

Deficits in facial emotion recognition occur frequently after stroke, with adverse social and behavioural consequences. The aim of this study was to investigate the neural underpinnings of the recognition of emotional expressions, in particular of the distinct basic emotions (anger, disgust, fear, happiness, sadness and surprise). A group of 110 ischaemic stroke patients with lesions in (sub)cortical areas of the cerebrum was included. Emotion recognition was assessed with the Ekman 60 Faces Test of the FEEST. Patient data were compared to data of 162 matched healthy controls (HC’s). For the patients, whole brain voxel‐based lesion–symptom mapping (VLSM) on 3‐Tesla MRI images was performed. Results showed that patients performed significantly worse than HC’s on both overall recognition of emotions, and specifically of disgust, fear, sadness and surprise. VLSM showed significant lesion–symptom associations for FEEST total in the right fronto‐temporal region. Additionally, VLSM for the distinct emotions showed, apart from overlapping brain regions (insula, putamen and Rolandic operculum), also regions related to specific emotions. These were: middle and superior temporal gyrus (anger); caudate nucleus (disgust); superior corona radiate white matter tract, superior longitudinal fasciculus and middle frontal gyrus (happiness) and inferior frontal gyrus (sadness). Our findings help in understanding how lesions in specific brain regions can selectively affect the recognition of the basic emotions.

Bonus Systems as Tools for \u2018Managing\u2019 Managers \u2013 the Behavioural Effects of Performance-Based Financial Rewards

In traditional reward systems, managers’ key performance indicators must surpass an agreed target in order to achieve a financial bonus. This system is designed to motivate high performance; yet adverse behavioural effects are often observed. These include middle managers becoming incentivised to game the reward system and target negotiation process they are subject to. This paper discusses three approaches to preventing such undesirable behavioural effects: Firstly, a linear pay-for-performance system without a target floor for receiving a performance bonus. Secondly, a bonus banking system where managers participate at the company’s losses as well as its gains. Thirdly, a proposal that uses the Beyond Budgeting approach which radically negates the core premises of the traditional reward system and replaces rewards for individual manager performance with those for wider team performance. These three approaches are compared and evaluated with respect to their potential to prevent unwanted manager behaviour, and on consideration of how effectively they may be operationalised.

In vitro coronal protein signatures and biological impact of silver nanoparticles synthesized with different natural polymers as capping agents.

Biopolymer-capped particles, sodium alginate-, gelatin- and reconstituted silk fibroin-capped nanosilver (AgNPs), were synthesized with an intention to study, simultaneously, their in vitro and in vivo haemocompatibility, one of the major safety factors in biomedical applications. Solid state characterization showed formation of spherical nanoparticles with 5 to 30 nm primary sizes (transmission electron microscopy) and X-ray photoelectron spectroscopy analysis of particles confirmed silver bonding with the biopolymer moieties. The degree of aggregation of the biopolymer-capped AgNPs in the synthesis medium (ultrapure water) is relatively low, with comparable hydrodynamic size with those of the control citrate-stabilized NPs, and remained relatively unchanged even after 6 weeks. The polymer-capped nanoparticles showed different degrees of aggregation in biologically relevant media – PBS (pH 7.4) and 2% human blood plasma – with citrate- (control) and alginate-capped particles showing the highest aggregation, while gelatin- and silk fibroin-capped particles revealed better stability and less aggregation in these media. In vitro cytotoxicity studies revealed that the polymer-capped particles exhibited both concentration and (hydrodynamic) size-dependent haemolytic activity, the extent of which was higher (up to 100% in some cases) in collected whole blood samples of healthy human volunteers when compared to that in the washed erythrocytes. This difference is thought to result from the detected protein corona formation on the nanoparticle surface in the whole blood system, which was associated with reduced particle aggregation, causing more severe cytotoxic effects. At the tested particle concentration range in vitro, we observed a negligible haemolysis effect in vivo (Balb/c mice). Polymer-capped particles did accumulate in organs, with the highest levels detected in the liver (up to 422 μg per g tissue), yet no adverse behavioural effects were observed in the mice during the duration of the nanoparticle exposure.

Intranasal Allopregnanolone Confers Rapid Seizure Protection: Evidence for Direct Nose-to-Brain Delivery

Allopregnanolone, a positive modulator of GABAA receptors with antiseizure activity, has potential in the treatment of seizure emergencies. Instillation of allopregnanolone in 40% sulfobutylether-β-cyclodextrin into the nose in mice rapidly elevated the seizure threshold in the timed intravenous pentylenetetrazol (ED50, 5.6 mg/kg), picrotoxin (ED50, 5.9 mg/kg), and bicuculline seizure tests. The effect peaked at 15 min, decayed over 1 h, and was still evident in some experiments at 6 h. Intranasal allopregnanolone also delayed the onset of seizures in the maximal PTZ test. At an allopregnanolone dose (16 mg/kg) that conferred comparable effects on seizure threshold as the benzodiazepines midazolam and diazepam (both at doses of 1 mg/kg), allopregnanolone caused minimal sedation or motor toxicity in the horizontal screen test whereas both benzodiazepines produced marked behavioral impairment. In addition, intranasal allopregnanolone failed to cause loss-of-righting reflex in most animals, but when the same dose was administered intramuscularly, all animals became impaired. Intranasal allopregnanolone (10 mg/kg) caused a rapid increase in brain allopregnanolone with a Tmax of ~5 min after initiation of the intranasal delivery. High levels of allopregnanolone were recovered in the olfactory bulb (Cmax, 16,000 ng/mg) whereas much lower levels (Cmax, 670 ng/mg) were present in the remainder of the brain. We conclude that the unique ability of intranasal allopregnanolone to protect against seizures without inducing behavioral adverse effects is due in part to direct nose-to-brain delivery, with preferential transport to brain regions relevant to seizures. Benzodiazepines are commonly administered intranasally for acute seizure therapy, including for the treatment of acute repetitive seizures, but are not transported from nose-to-brain. Intranasal allopregnanolone acts with greater speed, has less propensity for adverse effects, and has the ability to overcome benzodiazepine refractoriness. This is the first study demonstrating rapid functional central nervous system activity of a nose-to-brain-delivered steroid. Intranasal delivery circumvents the poor oral bioavailability of allopregnanolone providing a route of administration permitting its evaluation as a treatment for diverse neuropsychiatric indications.

Elevated lead levels in relation to low serum neuropeptide Y and adverse behavioral effects in preschool children with e-waste exposure

As a neurotoxicant, lead (Pb) primarily affects central nervous system, and particularly impacts developing brain. This study explores the associations of blood Pb level and children’s behavioral health. A total of 213 preschool children aged 3–7 years old were recruited from Guiyu (the e-waste-exposed area) and Haojiang (the reference area). The behavioral health of children was assessed using the ‘behavioral symptoms’ subscale of the Strengths and Difficulties Questionnaire (SDQ). Results showed that there was a significant difference in percent of children categorized as “at risk” between Guiyu (48.2%) and Haojiang (13.9%) (p < 0.001). The blood Pb level of children in Guiyu was significantly higher than those in Haojiang (median: 5.19 μg/dL vs. 3.42 μg/dL, p < 0.001). The serum Neuropeptide Y (NPY) was significantly lower in Guiyu children than those in Haojiang. Spearman correlation analyses demonstrated that blood Pb levels was negatively correlated with NPY (rs = −0.25, p < 0.001), but positively correlated with behavioral symptom scores; while serum NPY levels were negatively associated with behavioral symptom scores. Behavioral symptom scores were higher in children with blood Pb level ≥5.00 μg/dL (high) than those with blood Pb level < 5.00 μg/dL (low). After adjusting for confounding factors, children with lower NPY levels were at higher risk of having behavioral difficulties. In conclusion, Pb exposure in e-waste-exposed areas may lead to decrease in serum NPY and increase in the risk of children’s behavioral problems. In addition, NPY may mediate the association between Pb exposure and behavioral difficulties.

Target costing in electronics manufacturing – A case study

Target costing can constitute an integral part of new product development (NPD). Insights gained on the corresponding product can be the foundation of its market strategy, which again can be implemented using a Strategic Performance Management System (SPMS). This case study illustrates how TC and a Balanced Scorecard support the division head of an electronics manufacturing company in achieving their profitability goals. Specifically, it draws attention to adverse behavioral effects when the BSC does not fully reflect existing cause-and-effect relationships. The case may be utilized for instructional purposes in graduate/executive education.

P.592 Predictors of suicidal ideation and preparative behaviours in subjects with bipolar disorder: the contribution of the chronobiological dis-rhythmicity

Several lines of evidence indicate that anesthetic doses of the non-competitive N-methyl-D-aspartate receptor antagonist ketamine disrupt memory functions in rodents. The mechanism by which anesthetic ketamine produces its adverse behavioural effects is not yet clarified. The implication of nicotinic acetylcholine receptor as a potential site of action of anesthetic ketamine adverse effects on memory is proposed. We investigated the ability of α4β2 nicotinic receptor agonist ABT-418 (0.01, 0.03, 0.1 mg/kg, i.p.) and α7 nicotinic receptor agonist GTS-21 (0.3, 1, 3 mg/kg, i.p.) to counteract recognition memory deficits produced by acute post-training administration of anesthetic ketamine (100 mg/kg, i.p.) in rats. For this purpose, the novel object recognition test, a behavioural paradigm assessing recognition memory abilities in rodents was used. Post-training acute administration of GTS-21 (3 mg/kg) counteracted anesthetic ketamine-induced performance deficits in the novel object recognition memory task. By contrast, ABT-418 failed to reverse the recognition memory deficits caused by anesthetic ketamine. The present findings propose that an α7 nicotinic receptor component might modulate anesthetic ketamine’s adverse effects on recognition memory.

Psychiatric Comorbidities in Pediatric Epilepsy.

Psychiatric comorbidities are close to 5-times higher in children and youth with epilepsy (CYE) compared to general population. With epilepsy being one of the most common neurological disorders in children, we provide a timely review of psychiatric issues in CYE. A meta-analysis found a pooled prevalence of anxiety in 18.9% and depression in 13.5% of CYE. Attention deficit hyperactivity disorder (ADHD) is 2.5 to 5.5 times higher in CYE compared to healthy counterparts. Recent evidence highlights that behavioral adverse effects may lead to discontinuation of anti-epileptic drugs (AEDs) in more than 10% of CYE. Up to 70% CYE shows elevation in baseline psychological symptoms after AED initiation. Identifying psychiatric symptoms can be easily accomplished by the routine use of psychiatric screening instruments in CYE clinics, which is associated with improved health-related quality of life (HRQOL). Psychoeducation is a key component for any visit with CYE. There is some evidence of the effectiveness of behavioral psychological interventions for CYE. There are no therapeutic trials of psychotropics in CYE, but treatment recommendations based on the experience in adults with epilepsy and general population are applicable. Early diagnosis and management of psychiatric comorbidities leads to improvement in HRQOL of CYE. This requires routine screening and a multidisciplinary teamwork.

Sex-specific neurotoxic effects of early-life exposure to fluoride: A review of the epidemiologic and animal literature.

A growing body of evidence suggests adverse neurodevelopmental effects of early-life exposure to fluoride that may differ depending on timing of exposure and sex of the exposed. We conducted a literature search to identify the animal and human epidemiologic studies that examined sex-specific neurodevelopmental differences in response to prenatal and postnatal exposure to fluoride. Six of 138 animal studies and 15 of 106 human epidemiologic studies tested for sex-specific effects. Prenatal exposure to fluoride was associated with a male susceptibility to adverse behavioural effects in four of six animal studies and lower IQ in one of three prospective cohort studies. The body of evidence examining sex-effects associated with postnatal fluoride exposure was scarce, and many animal and cross-sectional human studies were considered to have a high risk of bias. Compared to females, male offspring appear to be more sensitive to prenatal, but not postnatal, exposure to fluoride. We discuss several sex-specific mechanisms and emphasize the need for future research.

Acute and Subacute Toxicity Studies of the Aqueous Extract from Haloxylon scoparium Pomel (Hammada scoparia (Pomel)) by Oral Administration in Rodents.

Materials and Methods Acute toxicity test was performed on Swiss albino mice at a single oral dose of 1-10 g/kg for 14 consecutive days. General behavioral adverse effects, mortality, and latency of mortality were determined. In the subacute study, the Haloxylon scoparium Pomel extract was administered orally at doses of 500, 1000, and 2000 mg/kg daily for 30 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined at the end of the experiment. Sections of livers and kidneys were removed for histological studies. Results Acute toxicity study showed that the oral LD50 value of Haloxylon scoparium Pomel extract was 5000 mg/kg. The subacute toxicity study of Haloxylon scoparium Pomel extract at doses 500, 1000, and 2000 mg/kg did not produce any observable symptoms of toxicity and no significant variation in body weight, organ weights, food, and water consumption or mortality in all treated rats. However, the administration of the Haloxylon scoparium Pomel extract to rats at 500 mg/kg and 1000 mg/kg showed a significant decrease in platelets. Moreover, only at the highest dose (2000 mg/kg), the extract caused a significant increase in red blood cells and hemoglobin. Our results showed that subacute treatments with Haloxylon scoparium Pomel extract at doses of 1000 mg/kg and 2000 mg/kg significantly elevated alkaline phosphatase and triglycerides. Histological studies showed that the subacute treatments of rats with Haloxylon scoparium Pomel extracts, at the doses 1000 and 2000 mg/kg, induced some histopathological changes in the livers but a slight changing in kidneys. Conclusion Our results indicated low acute toxicity of the aqueous extract of Haloxylon scoparium Pomel. Furthermore, daily oral administration of Haloxylon scoparium Pomel extract caused some damages to the livers of rats treated with high doses, expressed by an increase in some enzyme activities such as ALP. Regarding the renal function, we did not find remarkable toxicity in the subacute treatment with Haloxylon scoparium Pomel extracts at doses 1000 and 2000 mg/kg. However, further toxicity assessments should be done to ascertain the safety or the toxicity of this valuable plant species “Haloxylon scoparium pomel” in subchronic treatments.

Behavioral alterations associated with levetiracetam in pediatric epilepsy

Levetiracetam (LEV) has an improved pharmacological profile and is one of the most commonly used antiepileptic drugs (AEDs). However, associations between this pharmacological profile and behavioral side effects have been extensively reported in pediatric populations. We assessed behavioral changes after initiation of LEV, prescribed by the treating neurologist, in Chilean patients with epilepsy aged 4–15 years. A behavioral questionnaire was applied at baseline and at two, four, and twelve weeks of treatment. Thirty patients were enrolled: 16 males, 14 females, average age 8 years (range: 4–14). By week four, 23.3% of patients showed significant behavioral alterations that persisted throughout the observation period. No significant alterations emerged after four weeks in the remaining patients. Family history of psychiatric disease and prior behavioral difficulties were predisposing factors for adverse behavioral effects.Although previous studies associated adverse behavioral effects with LEV in pediatric patients with epilepsy, we believe that this is the first study to use a prospective methodology and standardized tools to quantify the symptomatology. Adverse behavioral effects may significantly affect quality of life for patients and families, diminishing the tolerability of treatment. To ensure successful therapy and improve medical decision-making, it is essential to consider predisposing factors for drug-related adverse effects and to regularly assess for behavioral alterations during treatment.

English

Camellia hakodae Ninh (CHN) is an ornamental plant of Vietnam, whose extracts is used as a potential phytotherapeutic beverage due to its good improvement in the immune system, reduction of inflammation and assisting the treatment of some chronic diseases. CHN production may be useful for health during this coronavirus epidemic period. This study aimed to evaluate the safety, acute and sub-chronic toxicity of aqueous extracts of CHN leaf in mice. In the acute toxicity study, CHN leaf at doses from 24.0 to 120.0 g/kg/day was given to 5 groups of Swiss mice by oral administration (equivalent in humans is 0.2 to 10 g/kg/day). Mice were observed for general behavioral changes, adverse effects and mortality up to 7 days post-treatment to find the highest dose that did not kill mice (the dose of death 0% (LD0)), the lowest dose that completely killed the mice (the dose of death 100% (LD100)) and the intermediate doses (LD50). In sub-chronic toxicity studies, CHN was given orally to 2 groups of Wistar rats at doses of 2.8 and 14 g CHN/kg/day (equivalent in humans is 0.4 and 2 g/kg) for 28 days taking CHN daily. After 28 days of taking CHN, mice were operated to observe the whole organ for histopathology. The microscopic structure of the liver, spleen, and kidney of at least 30% of mice in each group was randomly checked. The acute toxicity study in all the doses used did not cause any significant change as no LD50 was found. In addition, the sub-chronic toxicity study did not show any treatment-related abnormalities with regard to hematological and biochemical parameters. These results demonstrated that the CHN leaf aqueous extract is safe and does not appear to exert toxicity. Key words: Camellia hakodae Ninh, golden tea, acute and sub-chronic administration, Vietnamese tea. &nbsp

Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Internalizing Behaviors after Early Mild Traumatic Brain Injury.

Pediatric traumatic brain injury (TBI) can lead to adverse emotional, social, and behavioral consequences. However, outcome is difficult to predict due to significant individual variability, likely reflecting a complex interaction between injury- and child-related variables. Among these variables are genetically determined individual differences, which can modulate TBI outcome through their influence on neuroplasticity mechanisms. In this study, we examined the effect of Val66Met, a common polymorphism of the brain-derived neurotrophic factor gene known to be involved in neuroplasticity mechanisms, on behavioral symptoms of mild TBI (mTBI) sustained in early childhood. This work is part of a prospective, longitudinal cohort study of early TBI. The current sample consisted of 145 children between ages 18 and 60 months assigned to one of three participant groups: mild TBI, orthopedic injury, or typically developing children. Participants provided a saliva sample to detect the presence of the Val66Met polymorphism, and the Child Behavior Checklist was used to document the presence of behavioral symptoms at 6- and 18-months post-injury. Contrary to our initial hypothesis, at 6 months post-injury, non-carriers of the Val66Met polymorphism in the mTBI group presented significantly more internalizing symptoms (e.g., anxiety/depression and somatic complaints) than Val66Met carriers, who were similar to orthopedically injured and typically developing children. However, at 18 months post-injury, all children with mTBI presented more internalizing symptoms, independent of genotype. The results of the study provide evidence for a protective effect of the Val66Met polymorphism on internalizing behavior symptoms 6 months after early childhood mTBI.

The synthetic cannabinoid 5F-MDMB-PICA: A case series

5F-MDMB-PICA has been detected in products sold on the internet as well as in biological samples since 2016. It is associated with serious adverse health and behavioral effects and even death.Herein we report on twelve cases with proven 5F-MDMB-PICA consumption, including three fatalities, four cases of driving under the influence of drugs and five other criminal acts. In these cases, 5F-MDMB-PICA was detected in postmortem blood or serum. Concentrations ranged from 0.1–16ng/mL. In some blood (serum) and urine samples, the hydrolysis metabolite of 5F-MDMB-PICA (M12) could also be detected.In this case series, co-consumption with other drugs occurred in 9 of 12 cases, most commonly alcohol, cannabis and other contemporary SCs. In five cases, 4F-MDMB-BINACA was also detected.The described cases demonstrate various adverse effects that might be associated with 5F-MDMB-PICA. Observed physical adverse effects were mainly balance deficiencies and ocular effects such as reddened conjunctivae, glassy eyes and delayed or unresponsive pupil light reactions. Observed mental and behavioral effects were mainly changing moods, aggression, confusion, erratic behavior, mental leaps, disorientation, slowed reaction, logorrhea and slurred speech.Due to the fast changing market of synthetic cannabinoids, data on such new appearing substances are basically scarce. Because of the limited number of studies on pharmacological properties of synthetic cannabinoids, reports of findings in human samples along with corresponding case history descriptions can be valuable for the interpretation of upcoming routine cases.

Transient effects of chemotherapy for testicular cancer on mouse behaviour

The treatment of testicular cancer includes unilateral orchiectomy and chemotherapy and is curative for most patients. However, observational studies revealed an association with depression, anxiety and cognitive impairment. It is unclear whether these side effects are caused by chemotherapy, hemicastration or the disease itself. The aim of our study was to analyse the behavioural effects of hemicastration and chemotherapy in adult male mice. The animals were randomly divided into four groups – control, chemotherapy, hemicastration and hemicastration with chemotherapy. After chemotherapy that included three cycles of bleomycin, etoposide, cisplatin mice underwent a battery of behavioural tests. To assess the long-term effects animals were tested also 3 months after the end of treatment. Chemotherapy led to lower locomotor- and exploratory activity, higher anxiety-like behaviour and worse spatial memory immediately after treatment. These behavioural effects were not present three months later. Hemicastration had no effect on most of the observed outcomes. In conclusion, adverse behavioural effects induced by chemotherapy in mice are transient and disappear later in life. Further studies are needed to elucidate the mechanisms responsible for the observed effects.

The nicotinic α7 receptor agonist GTS-21 but not the nicotinic α4β2 receptor agonist ABT-418 attenuate the disrupting effects of anesthetic ketamine on recognition memory in rats

Several lines of evidence indicate that anesthetic doses of the non-competitive N-methyl-D-aspartate receptor antagonist ketamine disrupt memory functions in rodents. The mechanism by which anesthetic ketamine produces its adverse behavioural effects is not yet clarified. The implication of nicotinic acetylcholine receptor as a potential site of action of anesthetic ketamine adverse effects on memory is proposed. We investigated the ability of α4β2 nicotinic receptor agonist ABT-418 (0.01, 0.03, 0.1 mg/kg, i.p.) and α7 nicotinic receptor agonist GTS-21 (0.3, 1, 3 mg/kg, i.p.) to counteract recognition memory deficits produced by acute post-training administration of anesthetic ketamine (100 mg/kg, i.p.) in rats. For this purpose, the novel object recognition test, a behavioural paradigm assessing recognition memory abilities in rodents was used. Post-training acute administration of GTS-21 (3 mg/kg) counteracted anesthetic ketamine-induced performance deficits in the novel object recognition memory task. By contrast, ABT-418 failed to reverse the recognition memory deficits caused by anesthetic ketamine. The present findings propose that an α7 nicotinic receptor component might modulate anesthetic ketamine’s adverse effects on recognition memory.

The association between prenatal endocrine-disrupting chemical exposure and altered resting-state brain fMRI in teenagers.

Many studies have reported that prenatal exposure to endocrine-disrupting chemicals (EDCs) can cause adverse behavioral effects or cognitive dysfunction in children. This study aimed to investigate a relationship of the concentration of prenatal EDCs and brain function in teenagers. We recruited 59 mother-child pairs during the third trimester of pregnancy, and collected and examined the concentration of EDCs, such as heavy metals, phthalates and perfluoroalkyl substances (PFASs), in maternal urine and serum. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected in teenagers 13-16years of age, and fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) were performed to find the association between maternal EDC concentrations and the functional development of the teenage brain. We found a correlation between MBP concentration and activity in the superior frontal gyrus, middle frontal gyrus, middle temporal gyrus and inferior temporal gyrus in the combined group of boys and girls. We also observed a correlation between MBzP concentration and activity in the anterior cingulum gyrus and insula in girls. We found a correlation between lead concentration and activity in the cuneus in the combined group. We also observed a correlation between MeHg concentration and activity in the superior temporal gyrus, caudate nucleus and putamen in the combined group. The PFOS results revealed a negative relationship between activity in the right putamen in boys, girls and the combined group after phthalate or heavy metals were applied as covariates. The PFNA results showed a negative correlation between activity in the left/right putamen and left caudate nucleus in boys, girls and the combined group after phthalate, heavy metals or PFOS were applied as covariates. We examined the correlations between maternal EDC concentrations and brain development and found that the associations with resting-state teenage brains in some circumstances are sex-related.

Synthetic structural modifications of neurosteroid pregnanolone sulfate: Assessment of neuroprotective effects in vivo

Neuroactive steroid 20-oxo-5β-pregnan-3α-yl L-glutamyl 1-ester (PA-Glu), a synthetic analogue of naturally occurring 20-oxo-5β-pregnan-3α-yl sulfate (pregnanolone sulfate, PA-S), inhibits N-methyl-D-aspartate (NMDA) receptors and possesses neuroprotective properties and minimal adverse effects. Herein, we report in vivo effects of new structural modifications of the PA-S molecule: a nonpolar modification of the steroid D-ring (5β-androstan-3α-yl L-glutamyl 1-ester, AND-Glu), attachment of a positively charged group to C3 (20-oxo-5β-pregnan-3α-yl L-argininate dihydrochloride salt, PA-Arg) and their combination (5β-androstan-3α-yl L-argininate dihydrochloride salt, AND-Arg). The first aim of this study was to determine the structure-activity relationship for neuroprotective effects in a model of excitotoxic hippocampal damage in rats, based on its behavioral correlate in Carousel maze. The second aim was to explore side effects of neuroprotective steroids on motor functions, anxiety (elevated plus maze) and locomotor activity (open field) and the effect of their high doses in mice. The neuroprotective properties of PA-Glu and AND-Glu were proven, with the effect of the latter appearing to be more pronounced. In contrast, neuroprotective efficacy failed when positively charged molecules (PA-Arg, AND-Arg) were used. AND-Glu and PA-Glu at the neuroprotective dose (1 mg/kg) did not unfavorably influence motor functions of intact mice. Moreover, anxiolytic effects of AND-Glu and PA-Glu were ascertained. These findings corroborate the value of research of steroidal inhibitors of NMDA receptors as potential neuroprotectants with slight anxiolytic effect and devoid of behavioral adverse effects. Taken together, the results suggest the benefit of the nonpolar D-ring modification, but not of the attachment of a positively charged group to C3.

Bullying victimization and adverse health behaviors among school-going adolescents in South Asia: Findings from the global school-based student health survey.

Bullying among adolescentsis a global public health issue and has adverse behavioral and mental health consequences, yet a little is known about the relationship between bullying victimization and adverse health behaviors in adolescence in South Asian countries. Data for this cross-sectional analysis were extracted from the global school-based student health survey (GSHS) in Bangladesh (n = 2,989), 2014 and in Nepal (n = 6,529), 2015. Multivariate logistic regression analyses were used to identify the associations between bullying victimization and adverse health behaviors or outcomes: physical violence, sexual history, tobacco use, alcohol use, drug use, suicide ideation, plan, attempt, loneliness, and sleeping difficulty. The prevalence of bullying victimization that occurred for a minimum of 1 day during the 30 days preceding the survey was 24.5% in Bangladesh and 50.9% in Nepal. This study observed significant relationships between bullying victimization and several adverse health behaviors/outcomes. For example, in Bangladesh, the odds of attempted suicide were found to be higher in adolescents that experienced bullying for 1-2 (adjusted odds ratio [AOR]: 2.92; 95% confidence interval [CI]: 1.64-5.19), 3-5 (AOR: 3.55; 95% CI: 1.69), 6-9 (AOR: 5.33; 95% CI: 1.24-22.77), or 10 days or more (AOR: 9.83; 95% CI: 4.17-23.16) during the 30 days preceding the survey than who did not. Bullying among adolescents in school is common in Bangladesh and Nepal and is associated with several adverse health behaviors. Bullying and its potential health consequences are needed to be addressed in health promotion and programs in these countries.

Tamoxifen-induced acute mania: A case report.

Tamoxifen is widely used for the treatment of hormone-responsive breast cancer, osteoporosis, and post-menopausal symptoms. Also, tamoxifen is currently under investigation for its anti-manic properties. In this article, we report a case who developed manic episode following the initiation of tamoxifen and remitted with discontinuation of the medication. A 58-year-old woman was diagnosed with breast cancer. Pathologic diagnosis was invasive ductal carcinoma. Following bilateral total mastectomy operation, trastuzumab was initiated with intervals of 21 days. Five days before the fourth application of trastuzumab, tamoxifen was added. On the sixth day following the initiation of tamoxifen, manic symptoms were developed and she was diagnosed as acute mania. The oncology department suggested withdrawing tamoxifen due to a possible association between tamoxifen initiation and behavioral symptoms. Manic symptoms were rapidly (approximately 24 h) improved following cessation of tamoxifen. Psychiatric evaluation on the fifth day following cessation of tamoxifen revealed no manic symptoms. An aromatase inhibitor-exemestane was initiated and she showed no side effects with this medication since then. To our knowledge, this is the first case report of probable tamoxifen-induced mania. Our case report at least indicates that there were possibly some patients who were sensitive to the tamoxifen's nervous system effects, mainly to manic effects. In conclusion, clinicians should be aware of these rare behavioral adverse effects of tamoxifen.