A lifetime of challenges: real-life decision outcomes in early- and late-onset suicide attempters.

BACKGROUND: People who have attempted suicide display suboptimal decision-making in the lab. Yet, it remains unclear whether these difficulties tie in with other detrimental outcomes in their lives besides suicidal behavior. We hypothesize that this is more likely the case for individuals who first attempted suicide earlier than later in life. METHODS: A cross-sectional case-control study of 310 adults aged ≥ 50 years (mean: 63.9), compared early- and late-onset attempters (first attempt < 55 vs. ≥ 55 years of age) to suicide ideators, non-suicidal depressed controls and non-psychiatric healthy controls. Participants reported potentially avoidable negative decision outcomes across their lifetime, using the Decision Outcome Inventory (DOI). We employed multi-level modeling to examine group differences overall, and in three factor-analytically derived domains labeled Acting Out, Lack of Future Planning, and Hassles. RESULTS: Psychopathology predicted worse decision outcomes overall, and in the more serious Acting Out and Lack of Future Planning domains, but not in Hassles. Early-onset attempters experienced more negative outcomes than other groups overall, in Lack of Future Planning, and particularly in Acting Out. Late-onset attempters were similar to depressed controls and experienced fewer Acting out outcomes than ideators. LIMITATIONS: The cross-sectional design precluded prospective prediction of attempts. The assessment of negative outcomes may have lacked precision due to recall bias. CONCLUSIONS: Whereas early-onset suicidal behavior is likely the manifestation of long-lasting decision-making deficits in several serious aspects of life, late-onset cases appear to function similarly to non-suicidal depressed adults, suggesting that their attempt originates from a more isolated crisis.

Efficacy and Safety of FOLFIRINOX in Locally Advanced Pancreatic Cancer. A Single Center Experience.

The management of locally advanced pancreatic cancer (LAPC) is a major challenge. Although new drugs are available for the treatment of metastatic disease, the optimal treatment of non-metastatic cases remains controversial. The role of neoadjuvant therapy is still a question of debate in this setting. The aim of the study was to prospectively collect and analyse data on efficacy and safety of a modified FOLFIRINOX regimen in LAPC patients treated in a single institution. Another major objective was to assess the capability of FOLFIRINOX to render primary non-resectable cancer to resectable. No bolus fluorouracil was given and a 20% dose reduction of oxaliplatin and irinotecan was applied. Primary G-CSF prophylaxis was applied to prevent febrile neutropenia. Thirty-two patients (mean age 60.2 years, range: 40-77 years) have been enrolled into the study. All patients had ECOG performance status of 0 or 1. Best response to therapy was stable disease (SD) or partial regression (PR) in 18 (56.2%) and 6 (18.8%) cases. Two patients (6.3%) underwent surgical resection (100% R0). The most frequent grade 3/4 adverse events were nausea (18.8%), fatigue (12.5%) and diarrhea (12.5%). The incidence of severe neutropenia was 28.1%, with only one documented case of febrile neutropenia. The probability of disease progression was 25% and 50% after 75 and 160 days with 88.4% of possibility of disease progression after 500 days. OS probability was 92.1, 71.5% and 49.5% at 180-, 365 and 540 days. Our data does not support the capability of FOLFIRINOX to render primary non-resectable cancer to resectable. However, due to the high disease control rate observed, FOLFRINOX might be recommended as first line option for the palliative treatment of LAPC. Despite reduced chemotherapy doses significant toxicity has been seen.

The role of the different neoglottis forms in the development of esophageal voice.

UNLABELLED: Evaluation of voice quality parameters of esophageal speech in different neoglottis forms after total laryngectomy. METHODS: Presentation of voice analysis of 20 patients, who underwent total laryngectomy. The success of acquiring this technique was estimated by means of a voice analyzing program (pitch, sound-holding, loudness, spectrogram),and by the intelligibility via the telephone. Shape of the different types of neoglottis that developed and its functioning during vocalization and continuous speech were observed by nasal endoscopy. Data obtained from the voice analysis were compared among the observed three different neoglottis forms. RESULTS: The average dysphonia index of the 20 patients was 1.67 ± 0.38 (mean ± SD). Nasal fiberoscopic examination revealed three different types of neoglottis forms ­ a small mucosal button, two mucosal battens, and a mucosal lip. Voice quality of the esophageal speech of the patients with the mucosal button was found to be the closest to normal by subjective and objective acoustical evaluation. CONCLUSIONS: These findings emphasize the importance of the proper wound closure technique which can facilitate the development of a special button shape neoglottis form and help to acquire esophageal speech with the best quality parameters shortly after total laryngectomy.

Systemic urocortin 2, but not urocortin 1 or stressin 1-A, suppresses feeding via CRF2 receptors without malaise and stress.

BACKGROUND AND PURPOSE: Infusion of corticotropin-releasing factor (CRF)/urocortin (Ucn) family peptides suppresses feeding in mice. We examined whether rats show peripheral CRF/Ucn-induced anorexia and determined its behavioural and pharmacological bases. EXPERIMENTAL APPROACH: Male Wistar rats (n= 5-12 per group) were administered (i.p.) CRF receptor agonists with different subtype affinities. Food intake, formation of conditioned taste aversion and corticosterone levels were assessed. In addition, Ucn 1- and Ucn 2-induced anorexia was studied in fasted CRF(2) knockout (n= 11) and wild-type (n= 13) mice. KEY RESULTS: Ucn 1, non-selective CRF receptor agonist, reduced food intake most potently (~0.32 nmol·kg(-1) ) and efficaciously (up to 70% reduction) in fasted and fed rats. The peptides' rank-order of anorexic potency was Ucn 1 ≥ Ucn 2 > >stressin(1) -A > Ucn 3, and efficacy, Ucn 1 > stressin(1) -A > Ucn 2 = Ucn 3. Ucn 1 reduced meal frequency and size, facilitated feeding bout termination and slowed eating rate. Stressin(1) -A (CRF(1) agonist) reduced meal size; Ucn 2 (CRF(2) agonist) reduced meal frequency. Stressin(1) -A and Ucn 1, but not Ucn 2, produced a conditioned taste aversion, reduced feeding efficiency and weight regain and elicited diarrhoea. Ucn 1, but not Ucn 2, also increased corticosterone levels. Ucn 1 and Ucn 2 reduced feeding in wild-type, but not CRF(2) knockout, mice. CONCLUSIONS AND IMPLICATIONS: CRF(1) agonists, Ucn 1 and stressin(1) -A, reduced feeding and induced interoceptive stress, whereas Ucn 2 potently suppressed feeding via a CRF(2) -dependent mechanism without eliciting malaise. Consistent with their pharmacological differences, peripheral urocortins have diverse effects on appetite.

Differences in root functions during long-term drought adaptation: comparison of active gene sets of two wheat genotypes.

In an attempt to shed light on the role of root systems in differential responses of wheat genotypes to long-term water limitation, transcriptional differences between two wheat genotypes (Triticum aestivum L., cv. Plainsman V and landrace Kobomugi) were identified during adaptation to moderate water stress at the tillering stage. Differences in organ sizes, water-use efficiency and seed production were detected in plants grown in soil, and root functions were characterised by expression profiling. The molecular genetic background of the behaviour of the two genotypes during this stress was revealed using a cDNA macroarray for transcript profiling of the roots. During a 4-week period of moderate water deficit, a set of up-regulated genes displaying transiently increased expression was identified in young plantlets, mostly in the second week in the roots of Kobomugi, while transcript levels remained constantly high in roots of Plainsman V. These genes encode proteins with various functions, such as transport, protein metabolism, osmoprotectant biosynthesis, cell wall biogenesis and detoxification, and also regulatory proteins. Oxidoreductases, peroxidases and cell wall-related genes were induced significantly only in Plainsman V, while induction of stress- and defence-related genes was more pronounced in Kobomugi. Real-time qPCR analysis of selected members of the glutathione S-transferase gene family revealed differences in regulation of family members in the two genotypes and confirmed the macroarray results. The TaGSTZ gene was stress-activated only in the roots of Kobomugi.

Retropharyngeal superficial angiomyxoma.

OBJECTIVE: To describe the first published case of superficial angiomyxoma with an epithelial component occurring in the retropharynx. METHOD: Case report of a patient with swallowing difficulties caused by a rare case of superficial angiomyxoma in the retropharynx. RESULTS: Superficial angiomyxoma is a distinct entity among the dermal myxomatous lesions. Superficial angiomyxoma is poorly circumscribed, and local recurrence is common unless the tumour is excised with clear margins. Distinctive histological features include a myxoid mass composed of spindle and stellate-shaped cells and occasional multinucleated cells. There is prominent vasculature and a mixed inflammatory infiltrate in the stroma, particularly by neutrophil polymorphs. Epithelial structures are seen in about one-third of cases. A case of retropharyngeal tumour with morphological features of superficial angiomyxoma is reported. The tumour cells, including multinucleated ones, were negative for soft tissue differentiation markers. The inflammatory cells included lymphocytes, histiocytes and neutrophil polymorphs. CONCLUSION: This case demonstrates that a cutaneous type of angiomyxoma with epithelial-lined structures can occur in deep soft tissue, such as the retropharynx.

Periictal heart rate variability analysis suggests long-term postictal autonomic disturbance in epilepsy.

BACKGROUND: One of the possible pathomechanisms of sudden death in epilepsy (SUDEP) is a postictal dysregulation of autonomic nervous system. We performed a heart rate variability (HRV) analysis of the periictal state to analyze whether a cardiac autonomic disturbance exists after an epileptic seizure. METHODS: We included 31 periictal video-EEG-ECG recordings of 31 patients with epilepsy who had consecutively undergone pre-surgical evaluation. Nine generalized tonic-clonic (GTCS), 15 complex partial, and seven simple motor seizures were included. HRV was evaluated by analyzing 5-min-long ECG epochs, sampling from baseline, direct preictal, early-postictal (<15 min after the seizure), and late-postictal (5-6 h after the seizure) periods. RESULTS: The heart rate was elevated immediately after the seizures, but 5-6 h postictally returned to the baseline level. Time-domain components of HRV decreased after the seizure and this decrease lasted for 5-6 h. Low-frequency power decreased in the early-postictal phase and high-frequency power of HRV dropped in the late-postictal phase. GTCS had an impact on short-term but not on long-term postictal HRV decrease. CONCLUSIONS: We found decreased HRV immediately after the seizures, which lasted at least 5-6 h postictally, indicating a long-term postictal disturbance of the autonomous nervous system. GTCS were accompanied by a more decreased HRV than other seizures. Our results may have relevance in explaining pathomechanism of SUDEP.

Phase coupling between rhythmic slow activity and gamma characterizes mesiotemporal rapid-eye-movement sleep in humans.

In the human sleep literature there is much controversy regarding the existence and the characteristics of hippocampal rhythmic slow activity (RSA). Generally the human RSA is believed to occur in short bursts of theta activity. An earlier study, however, reported mesiotemporal RSA during rapid-eye-movement (REM) sleep that instead of theta fell in the delta frequency band. We conjectured that if this RSA activity is indeed a human analogue of the animal hippocampal theta then characteristics associated with the animal theta should also be reflected in the human recordings. Here our aim was to examine possible phase coupling between mesiotemporal RSA and gamma activity during REM sleep. The study relied on nine epilepsy surgery candidates implanted with foramen ovale electrodes. Positive half-waves of the 1.5-3 Hz RSA were identified by an automatic algorithm during REM sleep. High-frequency activity was assessed for 11 consecutive 20 Hz-wide frequency bands between 20 and 240 Hz. Increase in high frequency activity was phase coupled with RSA in most frequency bands and patients. Such a phase coupling closely resembles that seen between theta and gamma in rodents. We consider this commonality to be an additional reason for regarding delta rather than theta as the human analogue of RSA in animals.

Vectorial bicarbonate transport by Par-C10 salivary cells.

Salivary glands produce a HCO(3)(-)-rich fluid that is important for the neutral milieu in the upper gastrointestinal tract. The molecular mechanism of this secretion is poorly understood. Par-C10, an immortalized rat parotid acinar line, has been shown to secrete Cl(-)- in response to Ca(2+-)-mobilizing stimuli. Our aim was to assess the capacity of polarized monolayers of Par-C10 cells to transport and secrete HCO(3)(-)-. Transepithelial electrolyte movement was evaluated by short-circuit current measurements. Intracellular pH (pH(i)) was measured by microfluorometry in cells loaded with BCECF. Monolayers of Par-C10 cells, grown on Transwell membranes, developed high transepithelial resistance and exhibited vectorial anion secretion which was activated by both ATP and forskolin. The currents were partially inhibited by bumetanide and by withdrawal of HCO(3)(-) indicating the dependence of ion movements on NKCC and on HCO(3)(-) ions, respectively. In HCO(3)(-)-free solutions the recovery of pH(i) from acid loading was abolished by EIPA. In the presence of HCO(3)(-) there was a strong EIPA-insensitive recovery from acid loading which was inhibited by H(2)DIDS. ATP and forskolin stimulated HCO(3)(-) efflux from the cells. Furthermore, HCl(-) withdrawal experiments showed the presence of DNDS-sensitive basolateral anion exchange. In conclusion Par-C10 cells achieve transepithelial transport that is sensitive to both intracellular Ca(2+)- and cAMP-dependent stimulation. We identified Na(+)/H(+) exchange, Na(+)-HCO(3)(-) cotransport and anion exchange at the basolateral side of the cells as being involved in intracellular pH regulation and vectorial HCO(3)(-) secretion. This cell line offers a good model for further studies to understand the molecular mechanisms of salivary HCO(3)(-) secretion.

Prescriptions of NSAIDs to patients undergoing third molar surgery : an observational, prospective, multicentre survey.

BACKGROUND AND OBJECTIVES: Surgical extraction of an impacted third molar is generally followed by acute post-operative pain that has been shown to be primarily inflammatory. Thus, use of NSAIDs in this context is appropriate and has been shown to be effective. Several drugs are employed for this purpose, but no information exists on the reasons why preference is given to one rather than another. The principal objective of this study was to evaluate the pattern of administration of NSAIDs in patients undergoing surgery for impacted third molar extraction. The study also aimed to collect information on the efficacy, onset and duration of the analgesic effect of routinely prescribed NSAIDs and to assess the duration of treatment with these drugs and their tolerability. METHODS: This was an observational, multicentre, prospective survey. A total of 616 patients (38% male and 62% female) from the Italian Stomatology Clinics of the Universities of Bologna, Brescia, Cagliari, Chieti, Pavia, Pisa, Siena and Varese and from the Department of Oral and Maxillo-Facial Surgery of Semmelweis University, Budapest, were eligible for the study. Patients were evaluated over the 7 days following surgical extraction. NSAIDs were prescribed according to the normal prescribing habits of the centre and physician involved. The main outcomes of interest in the survey were the efficacy, onset and duration of analgesic effect, duration of therapy, and tolerability of the NSAIDs prescribed. RESULTS: Nimesulide was the most prescribed NSAID (68%), followed by diclofenac, ketoprofen and ibuprofen. Because of the low proportion of patients receiving other NSAIDs, these patients were considered a single treatment group for evaluation purposes. Nimesulide, especially when given before patients started experiencing pain after surgery, was more effective than other NSAIDs in reducing the severity of pain on the day of surgery, in delaying the time to maximum intensity of pain, in providing complete pain relief and in prolonging the duration of analgesic effect on the day of surgery. These results are consistent with the known anti-inflammatory and analgesic actions of nimesulide and with the important role of inflammation in the onset of pain after this type of surgery. CONCLUSION: These results confirm nimesulide as an effective reference drug for the treatment of post-operative dental pain and show that it has a positive benefit/risk profile in this setting.

REG can be used to detect cerebrovascular alteration caused by alcoholism.

Despite recent evidence of the beneficial effects of moderate alcohol consumption in arteriosclerosis prevention, the neurotoxic effects of alcohol abuse are well known. Our hypothesis was that uncontrolled alcohol consumption may cause cerebrovascular damage detectable by rheoencepholography (REG), a noninvasive bio-impedance technique for estimating cerebral blood flow. Test subjects were 48 alcoholic patients in Hungary; the control group consisted of 12 drug-addicted and depressed patients in Hungary and 13 healthy male subjects in the United States. Additional subgroups were formed according to smoking habits and average daily alcohol dose. REG was measured by a computer-based system, "Cerberus"; REG anacrotic time above 180 ms was considered pathological. ANOVA showed that daily alcohol consumption and smoking were significantly higher in alcoholics than in drug-addicted and depressed patients. Twelve alcoholics showed a pathological REG anacrotic time. Longer REG anacrotic time was correlated with higher daily alcohol consumption. In the alcoholic group, the steeper regression line of REG slope reflected the pathological impact of alcohol abuse. The healthy control sample showed a nearly identical slope for both REG and age. The correlation of increased REG anacrotic time and daily alcohol consumption supports the hypothesis that REG detects accelerated cerebrovascular aging (arteriosclerosis) in alcoholic subjects.

Orgasmic aura--a report of seven cases.

We report on seven patients who experienced an orgasmic aura at the start of their seizures. The patients (five women, two men) were aged 36-58. Three of seven patients described the exact nature of their auras only many years after their appearance, when the epilepsy diagnostic procedure became more intensive due to drug resistance. Moreover, one patient even refused any new therapeutical options due to the reportedly positive role of the orgasmic aura in her life. All of our patients had temporal lobe epilepsy. The clinical picture, EEG, MRI or SPECT findings suggested a right temporal epileptic focus in six patients, while in one patient the epileptogenic region was localised in the left temporal lobe. In the latter case, the left hemisphere was speech-dominant, while in the other cases no Wada tests were done. Our results confirm that orgasmic aura could be considered as an ictal lateralising sign to the right hemisphere, however, it has no 100% lateralising value.

Octopaminergic modulation of the membrane currents in the central feeding system of the pond snail Lymnaea stagnalis.

Octopamine is released by the intrinsic OC interneurons in the paired buccal ganglia and serves both as a neurotransmitter and a neuromodulator in the central feeding network of the pond snail Lymnaea stagnalis. The identified B1 buccal motoneuron receives excitatory inputs from the OC interneurons and is more excitable in the presence of 10 microM octopamine in the bath. This modulatory effect of octopamine on the B1 motoneuron was studied using the two electrode voltage clamp method. In normal physiological saline depolarising voltage steps from the holding potential of -80 mV evoke a transient inward current, presumably carried by Na(+) ions. The peak values of this inward current are increased in the presence of 10 microM octopamine in the bath. In contrast, both the transient (IA) and delayed (IK) outward currents are unaffected by octopamine application. Replacing the normal saline with a Na(+)-free bathing solution containing K(+) channel blockers (50 mM TEACl, 4 mM 4AP) revealed the presence of an additional inward current of the B1 neurons, carried by Ca(2+). Octopamine (10 microM) in the bath decreased the amplitudes of this current. These results suggest that the membrane mechanisms which underlie the modulatory effect of octopamine on the B1 motoneuron include selective changes of the Na(+)- and Ca(2+)-channels.

Reliability and precision of neural spike timing: simulation of spectrally broadband synaptic inputs.

Spectrally broadband stimulation of neurons has been an effective method for studying their dynamic responses to simulated synaptic inputs. Previous studies with such stimulation were mostly based upon the direct intracellular injection of noisy current waveforms. In the present study we analyze and compare the firing output of various identified molluscan neurons to aperiodic, broadband current signals using three types of stimulus paradigms: 1. direct injection in current clamp mode, 2. conductance injection using electrotonic coupling of the input waveform to the neuron, and 3. conductance injection using a simulated chemical excitatory connection. The current waveforms were presented in 15 successive trials and the trial-to-trial variations of the spike responses were analyzed using peri-stimulus spike density functions. Comparing the responses of the neurons to the same type of input waveforms, we found that conductance injection resulted in more reliable and precise spike responses than direct current injection. The statistical parameters of the response spike trains depended on the spectral distribution of the input. The reliability increased with increasing cutoff frequency, while the temporal jitter of spikes changed in the opposite direction. Neurons with endogenous bursting displayed lower reproducibility in their responses to noisy waveforms when injected directly; however, they fired far more reliably and precisely when receiving the same waveforms as conductance inputs. The results show that molluscan neurons are capable of accurately reproducing their responses to synaptic inputs. Conductance injection provides an enhanced experimental technique for assessing the neurons' spike timing reliability and it should be preferred over direct current injection of noisy waveforms.

Intentional seizure interruption may decrease the seizure frequency in drug-resistant temporal lobe epilepsy.

We investigated the nature of preictal subjective phenomena and whether they had any effect on the seizure frequency in 95 adult patients with medial temporal lobe epilepsy. Seventy-three (77%) patients indicated that they experienced seizure-provoking factors. Ten patients (11%) had prodromas independent of auras, while auras occurred in 89%. Forty-four patients (46%) reported that that they had tried to stop their seizures in the presence of prodroma or aura and this action had resulted in success at least once. Twenty-one patients (22%) regularly tried to stop their seizures because this effort was often successful according to their interpretation. Patients who reported that they could frequently inhibit their seizures had 1.8 +/- 1.6 seizures/month, a significantly lower mean seizure frequency than those 74 patients who did not do it regularly (4.6 +/- 4.8 seizures/month, P<0.001). Patients who reported regular experience in inhibiting intentionally their seizures more often had affective (P=0.05) and vertiginous auras (P<0.01) as well as isolated auras (P<0.05). Patients who experienced provoking factors showed the same seizure frequency as those who did not. Our results suggest that intentional seizure inhibition had an impact on the severity of drug-resistant epilepsy.

Misleading hallucinations in unrecognized narcolepsy.

OBJECTIVE: To describe psychosis-like hallucinatory states in unrecognized narcolepsy. METHOD: Two patients with hypnagogic/hypnapompic hallucinations are presented. RESULTS: Both patients had realistic and complex - multi-modal and scenic-daytime sexual hallucinations leading, in the first case, to a legal procedure because of false accusation, and in the second, to serious workplace conflicts. Both patients were convinced of the reality of their hallucinatory experiences but later both were able to recognize their hallucinatory character. Clinical data, a multiple sleep latency test, polysomnography, and HLA typing revealed that both patients suffered from narcolepsy. CONCLUSION: We suggest that in unrecognized narcolepsy with daytime hypnagogic/hypnapompic hallucinations the diagnostic procedure may mistakenly incline towards delusional psychoses. Daytime realistic hypnagogic/hypnapompic hallucinations may also have forensic consequences and mislead legal evaluation. Useful clinical features in differentiating narcolepsy from psychoses are: the presence of other narcoleptic symptoms, features of hallucinations, and response to adequate medication.

Automatisms with preserved responsiveness and ictal aphasia: contradictory lateralising signs during a dominant temporal lobe seizure.

The 25-year-old right-handed woman suffering from temporal lobe epilepsy (TLE) was referred to our centre for presurgical evaluation. MRI showed a right-sided hippocampal sclerosis. During video-EEG-recorded seizures, abdominal aura was followed by oral automatisms, during which she was completely reactive to external stimuli, although she was unable to speak. Ictal EEG showed right temporal seizure pattern, without contralateral propagation. She had abnormal speech postictally. Speech-activated functional transcranial Doppler sonography revealed right-sided speech dominance. She has become seizure free after a right-sided amygdalo-hippocampectomy. In our patient, contradictory clinical ictal lateralising signs (automatisms with preserved responsiveness vs. ictal and postictal dysphasia) occurred during right-, speech-dominant-sided seizures. This is the first report when automatisms with preserved consciousness occurred during a seizure originating and involving the speech-dominant hemisphere.

Orgasmic aura originates from the right hemisphere.

The authors present a patient with right mesiotemporal epileptogenic region who experienced orgasmic epileptic aura. Twenty-two similar published cases were also evaluated. Among 15 patients with unilateral EEG foci, 13 (87%) had right and 2 (13%) had left focus. All of the nine patients who had sufficient data on ictal onset area had right-sided seizure onset. The authors suggest that orgasmic aura is an ictal lateralizing sign to the right hemisphere.