Nitric Oxide Synthase activity in major depressive episodes before and after antidepressant treatment: Results of a large case-control treatment study.

BACKGROUND: Nitric oxide synthase (NOS) activity, an enzyme potentially involved in the major depressive episodes (MDE), could be indirectly measured by the L-Citrulline/L-Arginine ratio (L-Cit/L-Arg). The aim of this study was: (1) to compare the NOS activity of patients with a MDE to that of healthy controls (HC); (2) to assess its change after antidepressant treatment. METHODS: A total of 460 patients with a current MDE in a context of major depressive disorder (MDD) were compared to 895 HC for NOS activity (L-Cit/L-Arg plasma ratio). L-Arg and L-Cit plasma levels were measured using a MS-based liquid chromatography method. Depressed patients were assessed at baseline, and after 3 and 6 months of antidepressant treatment for depression severity and clinical response. RESULTS: Depressed patients had a lower NOS activity than HC at baseline [0.31 ± 0.09 v. 0.38 ± 0.12; 95% confidence interval (CI) -0.084 to -0.062, p < 0.0001]. Lower NOS activity at baseline predicted a higher response rate [odds ratio (OR) = 29.20; 95% CI 1.58-536.37; p = 0.023]. NOS activity in depressed patients increased significantly up to 0.34 ± 0.08 after antidepressant treatment (Est = 0.0034; 95% CI 0.0002-0.0067; p = 0.03). CONCLUSIONS: Depressed patients have a decreased NOS activity that improves after antidepressant treatment and predicts drug response. NOS activity may be a promising biomarker for MDE in a context of MDD.

[Predictive factors of seclusion duration in patients hospitalized in psychiatry settings. A prospective multisite study in the DTRF Paris-Sud]. / Facteurs prédictifs de la durée d'isolement chez les patients hospitalisés en psychiatrie. Une étude prospective multicentrique au sein du DTRF Paris-Sud.

INTRODUCTION: In psychiatric inpatient settings seclusion is a last resort to ensure the safety of the patient, other patients, and staff from disturbed behaviors. Despite its major interest for patients, seclusion could negatively impact treatment adherence and patient/staff relationships. Indeed, some secluded patients report a feeling of guilt during the measure and do not consider seclusion to be a healthcare intervention. To be more beneficial and to reduce the feeling by patients of being forced, seclusions should be as short and rare as possible. In other words, measures to reduce seclusion are available and have been clearly identified. Such measures could be applied, in the first instance, in patients with longer duration. In this way, the aim of this study was to investigate predictive factors of a seclusion of long duration. METHODS: Our study was based on the dataset of the EPIC study, an observational prospective French multicenter study of seclusion and restraint. The EPIC study occurred in seven French psychiatric hospitals in the southern region of Paris. Inclusions were realized for 73days and allowed a data collection of 302 seclusion measures. Of these measures 236 were effectively a seclusion in a standardized room. Because the median duration was 7days, we defined two groups of patients: duration<7days and duration ≥ 7 days. Our variable to be explicated was duration ≥ 7 days. Explicative variables available in EPIC study were age, sex, forced hospitalization, autoagressivity, heteroagressivity, use of sedative treatment (oral or intramuscular), history of seclusion and patient diagnoses. We used bivariate and multivariate analyses to explore the association between a seclusion duration ≥ 7 days and explicative variables. Diagnoses were classified as psychotic disorders, mood disorders and others diagnoses. To be included in multivariate logistic regressions, diagnoses were treated as dummy variables (mood disorder vs psychotic disorders; psychotic disorders vs others; mood disorders vs others). Statistical analyses were performed using SPSS software 20.0 and R 3.4.0. RESULTS: Of the 236 measures of seclusion the mean age was 38.2 (±12.8), 196 (83%) patients were forcibly hospitalized prior to their seclusion, 147 (62%) had a diagnosis of psychotic disorder, 43 (18%) a diagnosis of mood disorder and 33 (14%) an "other diagnosis". Mean duration was 10.2 (1.5) days and median was 7.1 days. One hundred and thirty-five (47%) patients were in the group of duration ≥ 7 days. In bivariate analyses, variables associated with a duration ≥ 7 days were: being in forced hospitalization prior to the seclusion (P=0.04), administration of a sedative treatment (P=0.01) and against the group of others diagnoses the diagnosis of mood disorders (P<0.0005) and psychotic disorders (P=0.001). Multivariate analyses showed that, against the group of other diagnoses, the group of psychotic disorders [OR=3.3, CI 95% (1.3-8.4), P=0.01], the group of mood disorder [OR=2.7, CI 95% (1.4-4.9), P=0.002] and administration of sedative treatment [OR=8.1, CI 95% (2.0-32.5), P=0.003] were significantly associated with a duration ≥ 7 days. These results were independent from other confusion variables. Considering the hospitalization status, psychotic disorders was the only diagnosis which showed an association between duration ≥ 7 days and forced hospitalization [OR=2.9 CI 95% (1.1-7.8), P=0.03]. CONCLUSION: Our study highlighted two profiles of higher risk to remain ≥ 7days in seclusion. The first one is patients with a diagnosis of mood disorder who needed sedative treatment. The second one is patients with a diagnosis of psychotic disorder who needed sedative treatment and forced hospitalized before seclusion. Thus, these two profiles could be a good target to practice, in the first instance, measures to reduce seclusion duration in psychiatry settings.

Evaluation of cold-weather wastewater nitrification technology for removal of polar chemicals of emerging concern from rural Manitoba wastewaters.

Aerated lagoons, typically used by small communities, often provide limited removal of wastewater nutrients. Given increasingly stringent wastewater standards, it is imperative that effective, but economical and easy-to-operate, treatment technologies be developed. The Submerged Attached Growth Reactor (SAGR®) is a treatment process developed to perform nitrification near freezing temperatures. Previous tests on full-scale installations have shown that SAGR could consistently remove ammonia to below current Canadian standards and provide additional total suspended solids and biochemical oxygen demand removal. In this study, we evaluated removal of polar chemicals of emerging concern (CECs), including pharmaceuticals, personal care products, and pesticides, at SAGR installations in two Manitoba First Nations communities (MCN and LPFN) under cold winter conditions. Both showed some removal of diclofenac, naproxen, clarithromycin, metoprolol, and trimethoprim, likely by biotransformation. Average naproxen removal was 21% (2.53 × 103 ng L-1) in MCN and 64% (1.58 × 103 ng L-1) in LPFN. Atenolol was well-removed by SAGR, by 80% on average (range of 64%-94%). Clarithromycin, metoprolol, and trimethoprim removal was similar within and between systems, ranging from 54% to 76% (30.8-3.07 × 102 ng L-1 removed). Carbamazepine was detected in nearly all samples, but was not well-removed, consistent with other treatment studies. Overall, results showed that SAGR technology could moderately remove CECs, while providing the designed treatment performance for other parameters. This work will help to improve our understanding of wastewater treatment in small and/or remote communities with limited infrastructure and challenging cold-weather conditions.

Peripheral nucleated red blood cells as a prognostic indicator in heatstroke in dogs.

BACKGROUND: Heatstroke in dogs is often fatal and is associated with a high prevalence of secondary complications. Peripheral nucleated red blood cells (NRBC) occur in dogs with heatstroke, but their association with complications and the outcome is unclear. HYPOTHESIS: Peripheral NRBC are common in dogs with heatstroke and have prognostic significance. ANIMALS: Forty client-owned dogs with naturally occurring heatstroke. METHODS: Prospective, observational study. Dogs were followed from presentation to discharge or death. Serum biochemistry and coagulation tests were performed at presentation. CBC and evaluation of peripheral blood smears were performed at presentation and every 12 hours. The relative and the absolute NRBC numbers were calculated. RESULTS: Presence of NRBC was observed in 36/40 (90%) of the dogs at presentation. Median relative and absolute NRBC were 24 cells/100 leukocytes (range 0-124) and 1.48 x 10(3)/microL (range 0.0-19.6 x 10(3)/microL), respectively. Both were significantly higher in nonsurvivors (22) versus survivors (18) and in dogs with secondary renal failure and DIC versus those without these complications. Receiver operator curve analysis of relative NRBC at presentation as a predictor of death had an area under curve of 0.92. A cut-off point of 18 NRBC/100 leukocytes corresponded to a sensitivity and specificity of 91 and 88% for death. CONCLUSIONS AND CLINICAL IMPORTANCE: Relative and absolute numbers of peripheral NRBC are clinically useful, correlate with the secondary complications, and are sensitive and specific markers of death in dogs with heatstroke, although they should never be used as a sole prognostic indicator nor should they replace clinical assessment.

The contribution of feathers in the spread of chicken anemia virus.

Chicken anemia virus (CAV) spreads vertically and horizontally, however, the process is mostly still obscure. To further clarify the horizontal CAV spread, we examined the contribution of feathers. We demonstrated that CAV could be amplified from DNA purified from feather shafts of experimentally infected chicks, and the process efficacy was evaluated by comparing the amplification of DNA purified from feather shafts and lymphoid organs of CAV-experimentally infected chicks. DNA from feathers was found as an efficient source for CAV detection. Further, to substantiate whether CAV reaches the feather shafts passively via the blood, or intrinsically, causing histopathological changes, the feather follicle tissues were examined for CAV-induced lesions. Specific histological changes were found, however, immunohistochemistry failed to detect viral proteins. To determine whether the feather shafts are a source of infective virus, they were homogenized and used to infect 1-day-old chicks via the mucosal entries (eyes, nose and oropharynx). That infection mode simulates the natural route of horizontal infection in commercial poultry houses. We demonstrated the CAV-infection by serology, virology and pathology, showing that feather shafts carry infectious CAV either on their surface or within their feather pulp, and concluded that feathers contribute to the horizontal CAV dissemination.

Modular organization of motor behavior in the frog's spinal cord.

The complex issue of translating the planning of arm movements into muscle forces is discussed in relation to the recent discovery of structures in the spinal cord. These structures contain circuitry that, when activated, produce precisely balanced contractions in groups of muscles. These synergistic contractions generate forces that direct the limb toward an equilibrium point in space. Remarkably, the force outputs, produced by activating different spinal-cord structures, sum vectorially. This vectorial combination of motor outputs might be a mechanism for producing a vast repertoire of motor behaviors in a simple manner.

Dry gangrene of the extremities in calves associated with Salmonella dublin infection; a possible immune-mediated reaction.

Dry gangrene of the extremities in calves is a circulatory error that may occur after infection with Salmonella dublin. This report describes an examination of three affected, 12 in-contact and five control calves, a main objective being to investigate the possible role of cold agglutination in pathogenesis. The lesions included dry gangrene of the hind legs, ears and tail. A cold agglutination test gave positive results in all animals examined except the controls. The three affected calves had high titres of S. dublin antibodies, as also did four of the in-contact animals. The results suggested a relationship between cold agglutination and the occurrence of the disease.

Atopic hypersensitivity to cis-dichlorodiammineplatinum(II) and other platinum complexes.

Allergic reaction to an antitumor agent, cis-dichlorodiammineplatinum(II) (DDP) was investigated. A 15-year-old white male with pulmonary metastases from embryonal carcinoma of testis was treated with a combination of DDP, bleomycin, and vinblastine. The dose of DDP varied from 2 to 2.25 mg/kg given i.v. He received 7 doses of DDP in 9 months. An anaphylactic reaction was seen within 3 min of the initiation of i.v. infusion of the 8th dose of DDP. The reaction was due to atopic hypersensitivity, as confirmed by an immediate wheal and flair reaction and increased histamine release from leukocytes with DDP. His serum IgE level was elevated. Neither the presence of chloride nor the amine grouping in DDP was essential for reactivity. The replacement of platinum with palladium abrogated the reactivity. There was no cross-reactivity with 3 other platinum complexes of known antitumor activity (platinum blue, platinum(II) 1,2-diaminocyclohexane malonate, and platinum(II) ethylenediamine malonate). This was also confirmed by the lack of reaction to subsequent i.v. administration of platinum(II) 1,2-diaminocyclohexane malonate (10 mg/kg) in this patient.

The Effect of Electromagnetic Field Treatment on Recovery from Ischemic Stroke in a Rat Stroke Model: Clinical, Imaging, and Pathological Findings.

Stroke is a leading cause of death and disability. Effects of stroke include significant deficits in sensory-motor skills and cognitive abilities. At present, there are limited effective interventions for postacute stroke patients. In this preliminary research we studied a new noninvasive, very low intensity, low frequency, electromagnetic field treatment (VLIFE), targeting a neural network, on an in vivo stroke rat model. Eighteen rats were divided into three groups: sham (M1) and two treatment groups which were exposed to VLIFE treatment for 4 weeks, one using theta waves (M2) and another using beta waves (M3); all groups were followed up for an additional month. Results indicate that the M2 and M3 treated groups showed recovery of sensorimotor functional deficits, as demonstrated by Modified Neurological Severity Score and forelimb placement tests. Brain MRI imaging results show a decrease in perilesional edema and lateral ventricle widening in the treated groups. Fiber tracts' imaging, following VLIFE treatment, showed a higher white matter integrity compared to control. Histological findings support neural regeneration processes. Our data suggest that VLIFE treatment, targeting a specific functional neural network by frequency rather than location, promotes neuronal plasticity after stroke and, as a result, improves clinical recovery. Further studies will investigate the full potential of the treatment.

[A case of liver abscesses in a bull]. / Een geval van leverabcessen bij een stier.

During a farm visit a breeding bull was presented with signs of anorexia, somnolence, and loss of condition. These signs were chronic and slowly progressive. Clinical examination revealed an enlarged liver and subsequent ultrasonography revealed multiple abscesses in the liver. This was confirmed during post-mortem examination. Ultrasonography, proved to be of great diagnostic value, especially because it is a quick and non-invasive procedure.

[A horse with a badly-healing wound? A case report]. / Een paard met een slecht genezende wond? Een case report.

A 14-year-old Haflinger mare was presented with a wound on the right metatarsus which it had sustained 3 years earlier. The wound had never completely healed but had only recently become a problem. Over a period of several months, the wound became larger, produced a lot of exudate, and the horse became lame on the affected limb. Clinical examination and radiographs failed to reveal the cause of the deterioration. Histological evaluation of tissue removed during debridement of the wound revealed squamous cell carcinoma. Because the tumour had already invaded the bone, the prognosis was unfavourable and the horse was euthanised. Necropsy showed the tumour to have metastasised to the right inguinal area and the adjacent mammary gland.

[Evaluation of the theoretical teaching of postgraduate medical students in France]. / Évaluation nationale de l'enseignement théorique du troisième cycle des études médicales en France.

OBJECTIVES: In France, medical students regularly complain about the shortcomings of their theoretical training and the necessity of its adaptation to better fit the needs of students. The goal was to evaluate the theoretical teaching practices in postgraduate medical studies by: 1) collecting data from medical students in different medical faculties in France; 2) comparing this data with expected practices when it is possible; 3) and proposing several lines of improvement. METHODS: A survey of theoretical practices in the 3rd cycle of medical studies was conducted by self-administered questionnaires which were free of charge, anonymous, and administered electronically from July 3 to October 31, 2013 to all medical students in France. RESULTS: National, inter-regional, regional and field internship educational content was absent in respectively 50.5%, 42.8%, 26.0% and 30.2% of cases. Medical students follow complementary training due to insufficient DES and/or DESC 2 training in 43.7% of cases or as part of a professional project in 54.9% of cases. The knowledge sought by medical students concerns the following crosscutting topics: career development (58.9%), practice management (50.7%), medical English (50.4%) and their specialty organization (49.9%). Fifty-four point one percent would like to be evaluated on their theoretical training on an annual basis. CONCLUSION: The results of this first national survey give insights into the theoretical teaching conditions in postgraduate medical education in France and the aspirations of medical students.

Effects of neonatal 6-hydroxydopamine treatment upon morphological organization of the posteromedial barrel subfield in mouse somatosensory cortex.

While recent studies indicate that proposed regulation of visual cortex plasticity by norepinephrine (NE) probably involves 6-hydroxydopamine (6-OHDA) effects other than NE depletion, reports of diminished neuronal maturation and reduced postweaning sensitivity to environmental conditions in animals treated with anti-adrenergic compounds continue to suggest a role for NE in neocortical development. To assess its possible role in development of a highly organized neocortical structure, the effects of postnatal 6-OHDA administration upon development of the somatosensory cortical posteromedial barrel subfield (PMBSF), which subserves the large facial whiskers, were observed in mice with whiskers in the middle row of the face removed unilaterally. Treatment with 6-OHDA caused 96-98% depletion of NE in parietal cortex. There were no effects of (or lesion interactions with) 6-OHDA treatment on barrel size in measures of Nissl-stained neurons, and 6-OHDA effects on numerical measures of dendritic branching of Golgi-impregnated non-pyramidal neurons in PMBSF were negligible. There were, however, effects of 6-OHDA treatment upon the highly ordered arrangement of dendrites within barrels. In 6-OHDA-treated animals, the class I (spiny and sparsely spined) cell dendrites were less attracted to the barrel hollow. In controls, for class I cells with their somata within the barrel wall, there was a high correlation between the distance from the soma to the hollow and the amount of dendrite in the wall, reflecting the distance the dendrite traverses to the hollow. In 6-OHDA-treated animals, this correlation was absent, i.e., cells at any distance from the hollow tended to have a high percentage of dendrite in the wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex difference in response of blood pressure to calcium antagonism in the treatment of moderate-to-severe hypertension.

BACKGROUND: The pressor response to examination in the clinic setting is called the 'white coat effect' (WCE). This response may be a confounder when investigators use clinic blood pressure as a measure of response to antihypertensive therapy. OBJECTIVE: ;To study the effect of the pressor response by evaluating the sex-specific effect of treatment with calcium antagonism on blood pressure measured in the clinic and by ambulatory blood pressure monitoring (ABPM). METHODS: Untreated hypertensive subjects (n=39) with seated clinic diastolic blood pressures (DBP) > or = 100 and < or = 130mmHg were studied. Same-day clinic systolic blood pressure (SBP) and ambulatory SBP were obtained after 1 week of placebo, and after 1 month of treatment with either nifedipine or verapamil in a randomized, blinded, parallel trial. RESULTS: With placebo, women s average SBP was 18+/-;4mmHg lower than clinic SBP. By contrast, men s average SBP with placebo was 4+/-15mmHg lower than clinic SBP. There was a significantly greater reduction in clinic SBP for women than there was for men after 1 month of treatment (by 33+/-13 versus 18+/-18mmHg, P<0.005). However, reduction in ambulatory SBP after 1 month was the same for both sexes (20+/-11 versus 19+/-12mmHg). CONCLUSIONS: In this study of moderate-to-severe hypertensives, the large WCE measured for women, which markedly diminished with treatment, accounts for the observed sex difference in response of clinic SBP to calcium antagonism. By contrast, with ABPM there was an equivalent response to treatment for both sexes. Use of ABPM could be a valuable means of eliminating the WCE as a confounder in clinical research.

Special problems of cancer care for the elderly.

This article focuses on the more common cancers; it does not attempt to cover the whole gamut of cancer in the elderly. Lung, pancreas, rectal, and stomach cancers are picked up sooner in the elderly than in the younger population, but bladder, breast, cervical, ovarian, thyroid, and uterine cancer, and malignant melanoma are diagnosed at a more advanced stage in the elderly, possibly because of inadequate routine screening of the elderly on the part of the physician.

Pathological findings in dogs with fatal heatstroke.

Eleven dogs with fatal heatstroke were examined grossly and histopathologically post mortem. All showed multi-organ haemorrhagic diathesis with coagulative necrosis. Hypaeremia and diffuse oedema were observed in the skin (eight dogs), lungs (11), brain (11) and bone marrow (one). Congestion of the splenic pulp (10 dogs) and hepatic sinusoids (nine) was also noted. Necrosis was observed in the mucosa of the small intestine (seven dogs), large intestine (eight), renal tubular epithelium (nine), hepatic parenchyma (eight) and brain neural tissue (four). The results showed that naturally occurring, fatal canine heatstroke induces acute multiple organ lesions affecting most body systems, and suggest that the more prevalent lesions include haemorrhagic diathesis, microthrombosis and coagulative necrosis. These are probable sequels of hyperthermia-induced disseminated intravascular coagulation and systemic inflammatory response syndrome, which lead to multi-organ dysfunction and death.