The onset of puberty in colony-housed male and female titi monkeys (Plecturocebus cupreus): Possible effects of oxytocin treatment during peri-adolescent development.

Oxytocin has been used to treat neurodevelopmental conditions in adolescent patients but possible effects on reproductive development have not been well investigated. The effects of daily intra-nasal oxytocin treatment (12-18 months of age) on puberty and fertility were studied in colony-housed, male and female titi monkeys (Plecturocebus cupreus). Body weight, urinary conjugated pregnanes and estrogens (defining cyclicity) in females, and androgens and sperm in urine of in males, were measured from 1 to 3 years of age to detect puberty. Serum testosterone was also measured in males at 13, 23 and 33 months of age and hemi-castration at 3 years of age enabled assessment of testicular morphometry and oxytocin receptor expression. An oxytocin treatment*time interaction suggested a minor, transient suppression in weight gain after treatment ended. Note that females weighed 10% less across all ages. Oxytocin-treated females exhibited early, spurious ovulations but neither regular cyclicity (≈30 months) nor pregnancies were affected by treatment. Oxytocin did not affect the pubertal increase in urinary androgen or the first appearance of sperm, which occurred as early as 15 months of age. Treatment did delay the puberty-associated rise in serum testosterone in males. All males were pubertal by 22 months and all females by 32 months of age. Although no major male or female fertility outcome was observed, oxytocin demonstrated some physiological effects through a delay of testosterone secretion in males, induction of precocious ovulation in females, and a suppression of general weight gain for the months following treatment.

Initiation of first disease-modifying treatment for multiple sclerosis patients in the Czech republic from 2013 to 2016: Data from the national registry ReMuS.

BACKGROUND: Proper management of multiple sclerosis (MS) requires feedback from clinical practice via registries. OBJECTIVE: To introduce the Czech national multiple sclerosis registry, ReMuS, and explore the availability and use of disease-modifying drugs (DMD). METHODS: The analysis focused on patients who started their first DMD, either with first-line or second-line medication and was based on reimbursement criteria set by Czech regulators. Baseline information was used to predict relapses after DMD initiation and to compare patients that started DMD in different years. RESULTS: A total of 3,328 patients started DMD treatment for MS between 2013 and 2016; 3,203 on first-line and 125 on second-line medication. The proportion of patients starting on second-line drugs increased from 1.8% in 2013 to 4.7% in 2016. The occurrence of a relapse within one year of DMD initiation was significantly related to (1) the Expanded Disability Status Scale (EDSS) score immediately prior to starting DMD and (2) the number of previous relapses. Both parameters were significantly lower in patients starting in later years of the explored interval. CONCLUSION: Data from the ReMuS registry highlights improvements made in the management of MS in the Czech Republic. However, a relatively low percentage of patients started treatment using second-line drugs, in contrast to trends in other countries.

Two New Species of Oxysarcodexia Townsend (Diptera: Sarcophagidae) From the Chaco Forest Ecoregion of South America.

Two new Neotropical species of the genus Oxysarcodexia Townsend (Diptera: Sarcophagidae) from Chaco ecoregion of Argentina are described, O. berthet, sp. nov. and O. ibera, sp. nov. Both species were recovered from localities in the eastern part of the Chaco forest (Humid Chaco). The descriptions are based on the male external morphology and terminalia. Photographs and SEM images are provided to aid in the identification of the species.

Assessment of the Abundance and Diversity of Calliphoridae and Sarcophagidae (Diptera) in Sites With Different Degrees of Human Impact in the Iberá Wetlands (Argentina).

The aim of the present study was to explore the diversity and describe the spatial distribution of Calliphoridae and Sarcophagidae along an urbanization gradient in the Iberá Wetlands. The flies were collected at 18 sampling points, three per site. In total, 3,318 flies were collected (3,077 blow flies and 241 flesh flies), distributed in 13 genera and 33 species. Calliphoridae was the most abundant, comprised 92.74% of all adult flies. Chrysomya albiceps (Wiedemann), Cochliomyia macellaria (F.), Chrysomya megacephala (F.), and Chrysomya putoria (Wiedemann) were the most abundant species, representing 82.21% of the total sample. The genus Oxysarcodexia Townsend was the most diverse with 10 species represented. The abundance of exotic species represents 62.85% of the total sample, showing a reduction toward less disturbed sites. The results of this study indicated that sites with intermediate impact had higher diversity than those where the disturbances are high or absent. Our findings provide the first assessment of Calliphoridae and Sarcophagidae diversity in the area of the Iberá Wetlands.

BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis.

BG-12, an immunomodulatory agent, reduces frequency of new gadolinium-enhancing (Gd+) lesions in relapsing multiple sclerosis (MS). This study reports the effect of 240 mg BG-12 orally three times daily (tid) for 24 weeks on the evolution of new Gd+ lesions to T1-hypointense lesions. Brain magnetic resonance imaging (MRI) scans from patients in placebo and 240 mg BG-12 tid arms of a phase 2b study were examined retrospectively. Included patients had at least one new Gd+ lesion from weeks 4 to 12. Week 24 scans were analyzed for number and proportion of new Gd+ lesions that evolved to T1-hypointense lesions. Eighteen patients receiving BG-12 and 38 patients receiving placebo were included in the analysis. The analysis tracked 147 new Gd+ lesions in patients from the BG-12 group and 221 Gd+ lesions in patients from the placebo group. The percentage of Gd+ lesions that evolved to T1-hypointense lesions was 34% lower with BG-12 treatment versus placebo (29%, BG-12; 44%, placebo; odds ratio 0.51; 95% confidence interval 0.43, 0.61; p < 0.0001). In addition to reducing frequency of new Gd+ lesions, BG-12 significantly reduced probability of their evolution to T1-hypointense lesions in patients with MS compared with placebo.

Safety of performing CT angiography in stroke patients treated with intravenous thrombolysis.

OBJECTIVE: Exposure to contrast agents may cause nephrotoxicity. The safety of performing CT angiography without having knowledge of the baseline creatinine level in stroke patients treated with tissue plasminogen activator (tPA) has not been established. METHODS: This is an observational cohort study, with a historical control group to evaluate the safety of CT angiography performed before tPA treatment given within 3 h of symptom onset. The CT angiography group represents all patients treated with tPA between September/2003 and November/2007 who had CT angiography. The control group consists of all patients treated with tPA between January 1999 and August 2003 when CT angiography was not performed. The primary outcome was a creatinine increase in 24-72 h compared with baseline; the secondary outcome was a creatinine increase by > or = 44 micromol/l in 24-72 h and the incidence of symptomatic intracerebral haemorrhage (sICH). RESULTS: Baseline parameters between the CT angiography group (164 patients, age 70+/-11; 91 male) and the control group (77 patients, age 67+/-11; 45 male) were similar. In the CT angiography group, the mean creatinine increase was -0.89 mmol/l and in the control group 2.2 mmol/l (p=0.42). A creatinine increase of > or = 44 micromol/l occurred in five patients (3%) in the CT angiography group and in three patients (4%) in the control group (p=0.50). Also, in the CT angiography group, eight patients (5%) had sICH as compared with three patients (4%) in the control group (p=0.73). CONCLUSION: Contrast agents given for CT angiography, performed in patients with normal and abnormal creatinine level, neither caused renal injury nor interfered with the safety of tPA treatment.

[Diabetes insipidus followed, after 4 years, with dysarthria and mild right-sided hemiparesis--the first clinical signs of Erdheim-Chester disease. Description and depiction of a case with a review of information on the disease]. / Diabetes insipidus, následovaný po 4 letech dysartrií a lehkou pravostrannou hemiparézou--první klinické príznaky Erdheimovy-Chesterovy nemoci. Popis a zobrazení prípadu s prehledem informací o této nemoci.

In 2004, diabetes insipidus was the first clinical sign of Erdheim-Chester disease in our patient. Following introduction of substitution therapy with adiuretin, the patient had no further health complaints for four years until 2008 when he gradually developed dysarthria and, consequently, movement disorder in the form of mild right hemiparesis. The first CNS CT scan (2004) did not reveal any pathology. The first pathological MRI of the brain in 2006 - thickening of pituitary stalk by pathological infiltration to 4-5 mm. During the following year, further infiltrates were detected in the CNS. The number and size of CNS infiltrates increased gradually on MRIs performed repeatedly up to 2008. Erdheim-Chester disease has become suspected based on PET-CT examination at the end of 2008. CT showed irregular structure of the skeleton with noticeable sclerotic foci in otherwise osteoporotic bone structure; changes were the most evident in the long bones of lower limbs, in the pelvic bones, skull and arms, while only one vertebra was affected from within the entire spine. Finding ofthickened aortic wall (up to 8 mm) as another pathological circumstance was consistent with the Erdheim-Chester disease-associated changes described as coated aorta. CT scan revealed clear fibrotic changes in the area of retroperitoneum. Applied fluorodeoxyglucose has accumulated in the bone foci described on CTscans as well as in the thickened wall ofthe thoracic and abdominal aorta (SUV 3.6). Tc-pyrophosphonate skeleton scintigraphy showed the same bone foci as PET-CT. Full body MRI showed pathological signal from the bone marrow of the above mentioned locations, particularly during STIR imagining, where there was clear abnormal signal corresponding to accumulated histiocytes, the higher signal of which was well-differentiated from the normal bone marrow. Measurement of bone mineral density with DEXA confirmed reduced density in lumbar vertebrae to the average value of - 2.7 SD (the lowest value was -3.1SD). The disease is associated with elevated inflammatory parameters: leucocytosis, thrombocytosis, elevated CRP and fibrinogen levels. Diagnosis was verified following histological assessment ofiliac bone marrow, where focal infiltrations with foamy histiocytes of typical immunophenotype (CD68+, CD1a-, S100-) were confirmed. Treatment was initiated with chemotherapy consisting of 2g/m2 of cyclophosphamide on day 1 and 200 mg/m2 of etoposide IV infusion on days 1-3, and followed by administration of 5 microg/kg of G-CSF and collection of haematopoietic peripheral blood stem cells (PBSC). PBSC collection was followed by 5-day administration of 5 mg/m2/day of 2-chlorodeoxyadenosine (Litac) administered to the patient at monthly intervals.

Serum inflammatory biomarkers in Parkinson's disease.

Numerous recent findings indicate the involvement of a neuroinflammatory reaction in the neurodegeneration in idiopathic Parkinson's disease (PD). We examined 29 consecutive patients with PD, ages 54-84 years, most of whom were moderately impaired (median UPDRS 19; Hoehn-Yahr 3; MMSE 28). A series of serum biomarkers were investigated, and their levels were correlated with the degree of the motor and cognitive impairment. There were no abnormalities of IL-6, acute phase proteins (C-reactive protein, serum amyloid A, alpha 1-antitrypsin, orosomucoid, ceruloplasmin, alpha 2-macroglobulin, transferrin, prealbumin) and factors of the complement system (C1q, C1-INH, C3, C4). A decrease in Mannan-binding lectin (MBL) levels was observed in six patients; an elevation of tumor necrosis factor-alpha (TNF-alpha) was found in 12 patients. No statistically significant correlation was found between the patient's clinical state (neuropsychologic and motor, as expressed by UPDRS III, Hoehn-Yahr, and MMSE) and the immunomarker changes. Our results indicate that the inflammatory process may be reflected in the serum; nevertheless, further research is needed to elucidate the possible clinical implications.

A pilot study on systemic thrombolysis followed by low molecular weight heparin in ischemic stroke.

Low molecular weight heparin (LMWH) administered immediately after intravenous thrombolysis (IT) may reduce the risk of arterial re-occlusion. Its benefit, however, may not outweigh the risk of intracranial hemorrhage (ICH). We sought preliminary data regarding safety of this combined therapy in an open-label, non-randomized study. The patients received either a standard anticoagulation (AC) starting 24 h after IT (the standard AC group) or AC with 2850 IU of nadroparin, given every 12 h immediately after IT (the early AC group). Sixty patients received IT treatment: 25 in the standard AC group [mean age 66, median National Institutes of Health Stroke Scale (NIHSS) 13, 64% men] and 35 in the early AC group (mean age 68, median NIHSS 13, 69% men). Symptomatic ICH occurred in one patient (4%) in the standard AC group and three patients (8.6%) in the early AC group [odds ratio (OR) 1.8; 95%CI 0.2-12.8]. At 3 months, nine patients in the standard AC group (36%) and 16 patients in the early AC group (45.7%) achieved a modified Rankin scale 0 or 1 (OR 1.2; 95%CI 0.5-3.2). Our study suggests that treatment with LMWH could be associated with higher odds of ICH, although it may not necessarily lead to a worse outcome. This justifies larger clinical trials.

Vaccination against nicotine does not prevent nicotine-induced changes in fetal nicotinic receptor binding and c-fos mRNA expression in rats.

Gestational exposure of rats to nicotine produces long-lasting alterations in brain development. Vaccination of adult female rats against nicotine reduces the distribution of maternally administered nicotine to fetal brain, suggesting that vaccination might protect against these effects. In the current study, the effects of vaccination on nicotine-induced changes in fetal (3)H-epibatidine binding and c-fos mRNA expression were evaluated using tissue from a previous pharmacokinetic study of vaccination. An intermittent nicotine dosing regimen designed to resemble nicotine intake in a smoker was administered from GD1-20. Peak nicotine levels in fetal brain were reduced by vaccination, whereas the chronic accumulation of nicotine in fetal brain was not. Gestational nicotine exposure produced significant increases in (125)I-epibatidine binding to brain and spinal cord on GD20, and decreased c-fos mRNA expression in fetal striatum, adrenal and lung. Vaccination did not significantly alter these effects. These data suggest that nicotine dosing, using a clinically relevant intermittent bolus dose regimen, produces substantial changes in fetal nicotinic receptor and c-fos mRNA expression. The decrease in c-fos mRNA expression contrasts with previously reported increases, and suggests that the nicotine dosing regimen used may influence its effects. The lack of effect of vaccination suggests that the cumulative exposure of fetal tissues to nicotine may influence the measured parameters to a greater extent than peak exposure levels.

Changes in maternal and fetal nicotine distribution after maternal administration of monoclonal nicotine-specific antibody to rats.

Vaccination against nicotine to elicit the production of nicotine-specific antibodies is a potential treatment for tobacco addiction which reduces nicotine distribution from serum to brain. Vaccination of pregnant rats also reduces the distribution of maternally-administered nicotine to the fetal brain. Whether this is due to maternal antibody reducing the transfer of nicotine from mother to fetus, or to fetal antibody altering the distribution of nicotine within the fetus, is not clear. In the current study, passive immunization of rats with the murine monoclonal nicotine-specific antibody Nic311 was used as a surrogate for vaccination because antibody transfer to the fetus was anticipated to be lower than with vaccination. Pregnant rats received nicotine from gestational day (GD) 18-20 as frequent i.v. boluses to simulate nicotine exposure from smoking. Nic311 was administered at doses of 30, 80 or 240 mg/kg on GD 19. Fetal serum Nic311 levels on GD 20 were <3% of concurrent maternal levels, but concentrations of up to 20 ug/ml in fetal serum were obtained owing to the very high levels in maternal serum. Accumulation of the chronically administered nicotine, measured on GD 20, was not changed by Nic311 treatment in either maternal or fetal brain. The early distribution of nicotine to maternal brain, measured 5 min after a dose, was markedly reduced by Nic311, while the early distribution of nicotine to whole fetus and fetal brain was not substantially altered. These data suggest that the limited transfer of Nic311 to the fetus in turn limits the ability of Nic311 to reduce nicotine distribution to the fetal brain.

Differential effects of passive immunization with nicotine-specific antibodies on the acute and chronic distribution of nicotine to brain in rats.

Vaccination against nicotine blocks or attenuates nicotine-related behaviors relevant to addiction in rats. Passive immunization with nicotine-specific antibodies is an alternative to vaccination with the potential advantages of allowing control of antibody dose and affinity. In the current study, the effects of two antibodies on the distribution of nicotine to brain were evaluated during chronic nicotine administration in rats; the monoclonal antibody Nic311 (K(d) = 60 nM) and nicotine-specific antiserum (K(d) = 1.6 nM). Nicotine was administered via repeated i.v. bolus doses over 2 days and antibody was administered during the first day. Neither antibody appreciably reduced the chronic accumulation of nicotine in brain, despite high protein binding of nicotine in serum (98.9%) and a 73% reduction in the unbound serum nicotine concentration with the highest Nic311 dose. However, both antibodies substantially reduced the early distribution of nicotine to brain 5 min after a dose. The higher affinity antibody was no more effective than Nic311. The highest Nic311 dose produced serum antibody levels 10 times higher than those reported with vaccination. The efficacy of Nic311 was dose-related, with the highest dose producing a 76% decrease in the early distribution of nicotine to brain. These findings, along with previous data, suggest that the primary effect of passive immunization is to slow, rather than prevent, the distribution of nicotine to brain. In the setting of chronic nicotine dosing, antibodies with a moderate affinity for nicotine produced substantial effects on the early distribution of nicotine to brain and were as effective as higher affinity antibodies.

Intracerebral event-related potentials to subthreshold target stimuli.

OBJECTIVES: Event-related potentials (ERPs) elicited by subthreshold visual stimuli were recorded directly from human frontal and temporal lobe structures to study unconscious perception. METHODS: Thirteen intractable epileptic patients undergoing depth electrode recordings prior to their surgical treatment participated in the study. An original method of modified visual oddball paradigm with supraliminal and subliminal stimuli was applied, and the averaged responses to both kinds of stimuli were subsequently compared. RESULTS: The results clearly prove that, at least from an electrophysiological viewpoint, the mechanism of unaware processing of visual stimuli in the human brain does not differ substantially from the aware processing. Finding the subliminal P3 waveform in a number of cortical structures (hippocampus and parahippocampal gyrus bilaterally, and left-sided mesiofrontal, orbitofrontal and lateral temporal cortex) indicates their involvement in unconscious processing, in spite of the fact that typical large-scale neurocognitive networks are not completely activated. The absence of activation consistently observed bilaterally in dorsolateral prefrontal cortices, in connection with right-sided cortical frontal lobe structures and right-sided lateral temporal neocortex in unconscious perception, supports the importance of these structures for the awareness of visual stimuli. The proof of the significantly faster unaware information processing represents another distinctive feature of implicit visual perception. CONCLUSIONS: Based on the presented findings and comparisons with the results of previous ERP, functional magnetic resonance imaging, positron emission tomography, and clinical neuropsychological studies, a crucial role of the large-scale neural system for conscious experience of perception is suggested, which is distributed extensively among the dorsal posterior association areas and the prefrontal cortex, with the dominant part being that of the right hemisphere.

The role of frontal and temporal lobes in visual discrimination task--depth ERP studies.

Visual event-related potentials were simultaneously recorded from different anatomical structures within frontal and temporal lobes in 12 epileptic patients. A simple discrimination task was performed to complement previous studies on the localization of P3 generators in the human brain. The role of multiple cortical structures in the generation of both P3a and P3b components was confirmed. Activities contemporary to a visual P3b were recorded in the hippocampus, amygdala and temporal pole. Anterior cingulate and orbitofrontal cortices-generated activities more closely related in time to the surface P3a. Earlier events related to visual discrimination took place in more lateral sites of the frontal lobe, but their contribution to the scalp P3 remains uncertain. Subsequently, mutual temporal relations among single generators were analyzed. The results suggested a processing-level hierarchy within the neural network for directed attention with a key role played by the dorsolateral prefrontal cortex.

Floppy eyelid syndrome: a diagnostic dilemma.

BACKGROUND: Floppy eyelid syndrome may be the underlining cause of papillary keratoconjunctivitis. Patients initially report a nonspecific irritation, redness, or a foreign body sensation. METHODS: As a result of its vague presentation, floppy eyelid syndrome is frequently misdiagnosed. A careful slit-lamp evaluation and a complete history aids in the diagnosis. CONCLUSIONS: The most distinctive feature of floppy eye syndrome is a pliant upper tarsus that is easily everted without excess manipulation. Histopathology has attributed the laxity of the lid to a decreased amount of elastin within the tarsus. Treatment includes prevention of the upper lid from everting during sleep or surgical procedures such as horizontal eyelid shortening. Our case report illustrates a patient with a classic case of floppy eyelid syndrome.

Effect of subthreshold target stimuli on event-related potentials.

OBJECTIVES: Event-related potentials (ERPs) elicited by subthreshold visual stimuli were studied to assess the relationship between unconscious cognitive processing and the electrical activity of the brain. METHODS: A new method of modified visual oddball paradigm with supraliminal and subliminal stimuli was applied. Prior to the experiment, the individual 'subjective' threshold for the conscious discrimination between frequent and target stimuli was established for each subject. Supraliminal and subliminal, frequent and target visual stimuli were then alternatively presented in random order to each subject. RESULTS: Both the individual and the grand average ERPs revealed a typical response (P3) in the parietal region after supraliminally presented target stimuli. In subliminal conditions an analogous positive deflection in the central-parietal region was observed, which was elicited by the target stimulus, but not the frequent stimulus. Its latency could be clearly distinguished from the latency of the classical P3, the time difference between the two waveforms was approximately 100 ms. RESULTS: The results of this study revealed the impact of unconscious processing to target stimuli on the configuration of event-related responses.

Adult onset foveomacular vitelliform dystrophy: a case report.

BACKGROUND: Pattern dystrophies of the retinal pigment epithelium, an arrangement of a pattern of dots, lines, or branches, are infrequent fundus abnormalities. Adult onset foveomacular vitelliform dystrophy (AOFVD) is considered a subtype of pattern dystrophy. Onset occurs during middle age, with an accumulation of yellow-gray macular deposits in the deeper retinal layers. Typically electro-oculograms are mildly subnormal or normal. Genetic studies suggest an autosomal dominant inheritance with variable penetrance. CASE REPORT: A case of a 56-year-old Hispanic women with a 1-month onset of "wavy moving vision" in both eyes is presented. Previous ocular and family history were unremarkable. Ophthalmoscopic examination revealed yellow circumscribed subretinal lesions of one-third to one-half disk diameter in the foveal centers of both eyes. Fluorescein angiography revealed a circumscribed area of mottled hyperfluorescence surrounding a central hypofluorescent spot. The patient was diagnosed with AOFVD. Examination of the patient's children revealed retinal pigment epithelial disturbances in the two oldest daughters, consistent with pattern dystrophies. CONCLUSION: Our investigation supports an autosomal dominant inheritance pattern, as seen on pedigree. The presence of different pattern dystrophies within the same family suggests a common etiologic continuum.

Excimer laser in situ keratomileusis.

We have been using a 193-nm excimer laser under protocol to ablate the corneal stromal bed after creating a hinged corneal flap with a microkeratome in order to reduce or eliminate refractive error. Thirty-one consecutive eyes are reviewed with a preoperative mean spherical equivalent refraction of -6.25 diopters (D) (range -3.50 to -11.75 D). Preoperative mean astigmatism was +0.87 D (range +0.25 to +2.75 D). At 6 months postoperatively, the mean spherical equivalent refraction was -0.50 D (range -3.50 to +2.00 D). Mean postoperative astigmatism was 0.64 D (range 0.25 to 3.50 D). A result within 1.00 D of attempted correction was achieved in 74.2% of eyes. Uncorrected visual acuity after a single procedure was 20/40 or better in 81% of eyes. Spectacle corrected visual acuity was unchanged in 26 (84%), decreased 1/2 line in 2 (6%), and increased 2 lines in 1 (3%). The incidence of postoperative complications was minimal. Excimer laser ablation in the stromal bed in combination with a hinged corneal flap seems to offer many advantages over excimer laser surface ablation with fewer complications.