Marine records reveal multiple phases of Toba's last volcanic activity.

The Indonesian Young Toba Tuff (YTT), classically dated around 74 ka BP, is considered as a short-lived explosive cataclysmic super-eruption. The huge amounts of ash and SO2 emitted are likely to have triggered a volcanic winter which accelerated the transition to the last glaciation, and may have induced a human genetic bottleneck. However, the global climatic impact of the YTT or its duration are hotly debated. The present work offers a new interpretation of the Toba volcanic complex eruptive history. Analysing the BAR94-25 marine core proximal to the Toba volcanic center and combining it with high-resolution tephrostratigraphy and δ18O stratigraphy, we show that the Toba complex produced a volcanic succession that consists of at least 17 distinct layers of tephra and cryptotephra. Textural and geochemical analyses show that the tephra layers can be divided in 3 main successive volcanic activity phases (VAP1 to VAP3) over a period of ~ 50 kyr. The main volcanic activity phase, VAP2, including the YTT, is likely composed of 6 eruptive events in an interval whose total duration is ~ 10 ka. Thus, we suggest that the eruptive model of the Toba volcano must be revised as the duration of the Toba volcanic activity was much longer than suggested by previous studies. The implications of re-estimating the emission rate and the dispersion of ashes and SO2 include global environmental reconstitutions, climate change modelling and possibly human migration and evolution.

Ejaculatory training lengthens the ejaculation latency and facilitates the functioning of the spinal generator for ejaculation of rats with rapid ejaculation.

A spinal pattern generator controls the ejaculatory response. Central pattern generators (CPGs) may be entrained to improve the motor patterns under their control. In the present study we tested the hypothesis that training of the spinal generator for ejaculation (SGE) by daily copulation until ejaculation, could promote substantive changes in its functioning permitting a better SGE control of the genital motor pattern of ejaculation (GMPE) and, as a consequence, a normalization of the ejaculation latency of rats with rapid ejaculation. To that aim, we evaluated in sexually experienced male rats with rapid ejaculation (1) the effects of daily copulation to ejaculation, following different entrainment schedules, on their ejaculation latencies, (2) the impact of these different ejaculatory entrainment schedules upon the parameters of the GMPE and (3) the possible emergence of persistent changes in the functioning of the SGE associated to the daily ejaculation entrainment schedules. The data obtained show that intense ejaculatory training of rats with rapid ejaculation lengthens the ejaculation latency during copulation and augments the ejaculatory capacity of the SGE in this population when spinalized. Thus, present data reveal that like other CPGs, the SGE can be trained and put forward that training of the SGE by daily copulation to ejaculation might be a promising alternative that should be taken into consideration for the treatment of premature ejaculation.

Current practice in Latin America of flexible ureterorenoscopy with laser for treating kidney stones. / Práctica actual de la ureteronefroscopia flexible con láser en América Latina para el tratamiento de la litiasis renal.

INTRODUCTION: The use of flexible ureterorenoscopy for treating kidney stones has increased in recent years, with considerable worldwide variation in the surgical technique and indications. OBJECTIVES: To determine the current practice, technique variations, use and indications of flexible ureterorenoscopy for treating kidney stones in Latin American. METHODS: We sent (by email and web link) an anonymous questionnaire with 30 questions on flexible ureterorenoscopy for treating kidney stones to Latin American urologists from January 2015 to July 2015. We collected the responses through the Survey Monkey system. RESULTS: A total of 283 urologists in 15 Latin American countries participated (response rate, 10.8%); 254 answered the questionnaire completely; 52.8% were urologists from Mexico and 11% were from Argentina; 11.8% of the responders stated that they performed >100 cases per year; 15.2% considered ureterorenoscopy as the treatment of choice for stones >2cm, and 19.6% performed ureterorenoscopy in single stages for calculi measuring >2.5cm. Some 78.4% use fluoroscopy, 69.1% use a ureteral sheath in all cases, 55.8% place double-J catheters at the end of surgery, 37.3% considered a stone-free state to be 0 fragments, and 41.2% use plain radiography to assess the stone-free condition. CONCLUSIONS: Most participating urologists consider flexible ureterorenoscopy as the first-choice treatment for stones <2cm; a small percentage of these urologists perform >100 ureterorenoscopies per year. More than half of the urologists routinely used fluoroscopy and ureteral access sheath; the most common method for determining the stone-free state is plain abdominal radiography.

Unraveling the modulatory actions of serotonin on male rat sexual responses.

Animal studies and clinical investigations reveal that serotonin plays a central role in the control of the ejaculatory threshold. The chronic use of selective serotonin reuptake inhibitors (SSRIs) frequently results in sexual dysfunction, inviting to analyze the modulatory actions of serotonin on male sexual function in depth. Even though the main effect of serotonin on male sexual responses is inhibitory, this neuromodulator also mediates brief important stimulatory actions. Serotonin (5-HT) can activate two intracellular signaling pathways: a lower-threshold facilitatory pathway, and a higher-threshold inhibitory pathway, leading to biphasic effects. We propose that these divergent actions are related to the stimulation or inhibition of glutamatergic and GABAergic interneurons. Experimental evidence suggests that low 5-HT concentrations produce stimulatory actions on male ejaculatory aspects that might be mediated by the blockade of the GABAergic neurotransmission in the MPOA and spinal cord, which in turn releases a tonic inhibition that allows other neurotransmitters such as glutamate, noradrenaline, oxytocin and dopamine to initiate a sequence of molecular events resulting in the expression of ejaculation. Similar serotonin actions, mediated via interneurons, have been proposed for the regulation of other processes and occur in many central nervous system areas, indicating that it is not an isolated phenomenon.

Effects of bupropion on the ejaculatory response of male rats.

Chronic antidepressant treatment is associated with sexual side effects, particularly affecting the ejaculatory response. Bupropion (BP), an antidepressant inhibiting dopamine/noradrenaline reuptake, seems to have a low impact upon male sexual function. Ejaculation is regulated both at the brain and spinal cord by the spinal generator for ejaculation (SGE). We investigated the effects of chronic BP treatment on ejaculatory behavior and on SGE functioning. Sexually experienced male rats were intraperitoneally (i.p.) injected with BP (7.5 or 15 mg kg(-1)) during 14 days and tested for sexual behavior on days 1, 7 and 14 of treatment; these same males were used to evaluate the functioning of the SGE by recording the genital motor pattern for ejaculation (GMPE). Acute and chronic BP administration did not importantly modify copulatory behavior of male rats. Chronic treatment with the low dose of BP produced deficits in the functioning of the SGE that were restored by activation of the SGE through afferent stimulation. Conversely, chronic treatment with the high-dose of BP disrupted the functioning of the SGE, as the deficits were not compensated by activating the SGE through sensory stimulation. It is concluded that chronic BP at high doses alters the functioning of the SGE.

Rhythmic motor patterns accompanying ejaculation in spinal cord-transected male rats.

A spinal pattern generator controls the ejaculatory response. Activation of this spinal generator elicits rhythmic motor patterns of the striated musculature that surrounds the genital tract that contributes to the expulsion of seminal secretions. In the present study, we elicited ejaculation in spinal cord-transected male rats by mechanically stimulating the urethra and registered rhythmic motor patterns in the cremasteric, iliopsoas and pubococcygeus muscles. The rhythmic motor activity recorded in these muscles was compared with that elicited in the bulbospongiosus muscles; the results revealed similarities in the motor parameters among all the muscles. Data of this study, showing the occurrence of rhythmic motor behaviour in the cremasteric, iliopsoas and pubococcygeus muscles during ejaculation, suggest that these muscles might be under the control of the spinal generator for ejaculation.

DWI findings in a iatrogenic lumbar epidermoid cyst. A case report.

Epidermoid cysts comprise less than 1% of intraspinal tumors. They can be congenital, frequently associated with other spinal malformations, or iatrogenic, resulting from the implantation of epidermal cells within the spinal canal during the execution of a variety of procedures such as spinal puncture. At MR imaging epidermoid tumors can mimic cystic lesions with fluid content such as arachnoid cysts. DWI can help obtain a correct diagnosis. We describe a case of iatrogenic lumbar epidermoid cyst with DWI findings in a young woman who had undergone epidural anesthesia for Cesarean section three years before the onset of symptoms.

Large capillary telangiectasia and developmental venous anomaly of the Basal Ganglia: an unusual finding.

Brain capillary telangiectasias are small, benign, asymptomatic, angiographically occult lesions that are incidentally discovered either at autopsy or on MR imaging in most cases. They are commonly located in the pons and can be associated with other vascular malformations. We describe a case of an unusually large capillary telangiectasia associated with a developmental venous anomaly involving the basal ganglia in a young woman, in which MR serial imaging suggested the diagnosis and avoided an unnecessary stereotaxic biopsy.

[Morpho-functional iterative surgery in a patient with von Recklinghausen disease]. / Chirurgia reiterativa morfofunzionale in paziente con malattia di von Recklinghausen. Case report.

Neurofibromatosis 1 is an autosomal dominant disease with an estimated incidence 1:2500 to 1:3000 live newborns. The disease presents with multiple cutaneous and non cutaneous lesions. NF1 occurs with equal frequency in males and females and has been identified in all ethnic group. The morbidity and the mortality caused by NF1 are the result of complications that may involve any of the body systems. This disease has been linked with mutations of the NF1 gene which encodes tumor suppressor neurofibromin. At least half of patients with NF1 will have only cutaneous involvement that is not considered to be a major medical problem, even though it can be a source of psychologic burden as a result of cosmetic disfigurement. The cardinal features of the disorder are cafè-au-lait spots, axillary freckling, cutaneous neurofibromas and Lisch nodules, but there are a lot of wide variety of complications affecting almost every system of the body, including the eyes (optic glioma), the nervous system (intracranial tumors), the skeleton (short stature, scoliosis), the endocrine and cardiovascular system (hypertension). Manifestations of NF1 vary at different times in an individual's life. Substantial variability exists among affected members of a single family. This variability confounds clinical management and the severity of the disease cannot be predicted. We present a case in young woman 24 years-old treated by reiterative plastic surgery.

DMI-induced sexual effects in male rats: analysis of DMI's acute and chronic actions on copulatory behavior and on the genital motor pattern of ejaculation.

Desipramine (DMI) is a tricyclic antidepressant that alters male sexual function. This work was designed to study the effects of acute and chronic DMI treatments on male rat copulatory behavior, discriminating between spinal and behavioral DMI actions on the ejaculatory response. To this aim, sexually experienced male Wistar rats received DMI (7.5 or 15 mg/kg, i.p.) for 14 days and were tested for sexual behavior on Days 1, 7 and 14 of treatment. Besides, the genital motor pattern of ejaculation (GMPE) was recorded in anaesthetized, spinal male rats after acute (1-10 microg, i.v.) or 14-day chronic DMI (15 mg/kg, i.p.) treatment. Results showed that acute and chronic DMI treatments reduced the ejaculatory threshold by decreasing intromission number and ejaculation latency of male rats, in successive copulatory series. The intensity of the effects depended on the dose and treatment duration. DMI acute treatment activated GMPE expression only at the lower doses and these responses exhibited modified parameters. Chronic DMI reduced the number of discharges and increased the frequency of discharge of spontaneous GMPE responses, affected mechanically evoked ones and increased the number of GMPEs expressed after repeated genital stimulation as compared to control rats. DMI treatments affected copulatory behavior both at brain and spinal levels and its effects on ejaculation, assumed to be similar in behavioral and spinal models, differed.

[Lack of assertiveness in patients with eating disorders]. / Trastornos de la conducta alimentaria y asertividad.

BACKGROUND: Low self-assertion has been noted as an important feature among patients with eating disorders. AIM: To verify, in a female population, if assertiveness is related or has a predictive capacity for the development of eating disorders. SUBJECTS AND METHODS: An structured clinical interview, the Eating Attitudes Test (EAT-40) and the Rathus Assertiveness Scale (RAS) were administered to 62 patients that fulfilled the DSM-IV diagnostic criteria for eating disorders and to 120 female students without eating problems. RESULTS: Patients with eating disorders ranked significantly higher on the EAT-40 and its factors (p <0.001) and showed a lower level of assertiveness on the RAS (p <0.001). Assertiveness measured by RAS and its factors was inversely related to EAT-40 and its items (r= -0.21). The predictive capability of the lack of self-assertion in the development of an eating disorder reached 53%, when patients with eating disorders and subjects at risk were considered together and compared to students without such disorder. CONCLUSIONS: Lack of assertiveness is a significant trait in patients with eating disorders; it may worsen its outcome and even perpetuate symptoms. Low self-assertion may be considered a predictive factor in the development of an eating disorder and must be managed from a preventive or therapeutic point of view.

Evidence for the presence of the spinal pattern generator involved in the control of the genital ejaculatory pattern in the female rat.

Substantial progress has been made during recent years in elucidating the control of male ejaculatory function by the central nervous system. These efforts have revealed the participation of a central pattern generator in the control of ejaculation. There is a strong similarity in the neural organization of male and female sexual functions. In the present study, the hypothesis that the spinal generator for ejaculation was present and functional in the female rat was evaluated. To this purpose, the expression of the ejaculatory motor pattern and its pharmacological activation in spinally transected female rats were investigated. Results revealed the presence in females of the already described rhythmic ejaculatory motor pattern of male rats. This ejaculatory motor pattern could be registered in the urethralis muscle of the female rat after mechanical stimulation of the urethra, vagina and clitoris and consisted, as in the male rat, of a first ejaculatory motor train followed by an after-discharge component. Besides, the female genital ejaculatory motor pattern could be pharmacologically induced by the systemic injection of sodium nitroprusside with similar motor characteristics. No significant differences between the sensorial and pharmacologically induced female genital motor patterns were found. Present findings provide evidence for the presence of the genital motor pattern of ejaculation in female rats and suggest that the spinal generator for ejaculation is also present and functional in this gender.

Trastornos de la conducta alimentaria y asertividad / Lack of assertiveness in patients with eating disorders

Background: Low self-assertion has been noted as an important feature among patients with eating disorders. Aim: To verify, in a female population, if assertiveness is related or has a predictive capacity for the development of eating disorders. Subjects and methods: An structured clinical interview, the Eating Attitudes Test (EAT-40) and the Rathus Assertiveness Scale (RAS) were administered to 62 patients that fulfilled the DSM-IV diagnostic criteria for eating disorders and to 120 female students without eating problems. Results: Patients with eating disorders ranked significantly higher on the EAT-40 and its factors (p <0.001) and showed a lower level of assertiveness on the RAS (p <0.001). Assertiveness measured by RAS and its factors was inversely related to EAT-40 and its items (r= -0.21). The predictive capability of the lack of self-assertion in the development of an eating disorder reached 53%, when patients with eating disorders and subjects at risk were considered together and compared to students without such disorder. Conclusions: Lack of assertiveness is a significant trait in patients with eating disorders; it may worsen its outcome and even perpetuate symptoms. Low self-assertion may be considered a predictive factor in the development of an eating disorder and must be managed from a preventive or therapeutic point of view.

alpha-Adrenergic agents modulate the activity of the spinal pattern generator for ejaculation.

Spinal cord transection at a thoracic level activates fictive ejaculation (FE) in the male rat. It has earlier been demonstrated that fictive motor patterns may be activated by pharmacological means and that the noradrenergic system seems to be particularly efficient in triggering locomotor fictive patterns in spinal animals. In the present study, the hypothesis was tested that the spinal noradrenergic system participates in the activation of the spinal generator for ejaculation (SGE). To this aim, the effect of the adrenergic agents, methoxamine, prazosin, clonidine, and yohimbine, upon FE was evaluated in spinal male rats using electromyographic techniques. The results obtained show that ejaculatory rhythmic patterns, accompanied by the expulsion of urethral contents and phasic penile movements, can be elicited by the intravenous (i.v.) injection of methoxamine or yohimbine. These drug-induced motor sequences appear superimposed to the intrinsic ejaculatory spinal rhythm. By contrast, i.v. injection of prazosin or clonidine blocked the expression of the spontaneous ejaculatory rhythmic pattern without inducing any other genital response. These data suggest that an increased noradrenergic tone, either by blockade of presynaptic alpha2-adrenoceptors or by stimulation of postsynaptic alpha1-adrenoceptors, results in the activation of the SGE. Present findings provide the evidence that the SGE might be importantly influenced by the noradrenergic system, which exerts a facilitatory control on the expression of the genital motor pattern of ejaculation.

Evidence for the presence and functioning of the spinal generator for ejaculation in the neonatal male rat.

A spinal pattern generator controls ejaculation in the male rat. In the present study, the hypothesis that the spinal generator for ejaculation was functional at early postnatal stages was evaluated. To this purpose, the expression of the ejaculatory motor pattern and its pharmacological activation in spinally transected neonatal rats from postnatal day 2 to weaning were investigated. Results revealed the presence of the rhythmic ejaculatory motor pattern in neonatal male rats. As in adult sexually experienced animals, the neonatal ejaculatory motor pattern could be elicited after the application of an ejaculation-like-releasing stimulus. The rhythmic genital motor response of neonates exhibited a gradual maturation that was reflected in its motor parameters until showing the features of the adult response at postnatal day 28. Besides, the ejaculatory motor pattern could be induced by the systemic injection of oxytocin in 7-day-old neonates as well as in adult animals. Present findings provide evidence for the presence of the spinal generator for ejaculation early during postnatal development, suggesting that its organisation is innate.

Role of genital sensory information in the control of the functioning of the spinal generator for ejaculation.

An intrinsic spinal rhythm mediates fictive ejaculation (FE). In this study, the effect of genital sensory stimulation on the functioning of the spinal generator of ejaculation was investigated. To this aim, the effect of (a) stimulation of internal and external genital structures; (b) repeated elicitation of FE and (c) genital stimulation during in progress expression of FE on the rhythmic genital motor pattern of ejaculation (GMPE) was analysed in sexually experienced, spinal male rats. Results showed that the spinal intrinsic ejaculatory rhythm can be modulated by genital inputs, and that repeated stimulation modifies this rhythm, progressively inhibiting its expression. Finally, in progress GMPEs could be reset by overlapping genital stimulation, supporting the notion of the spinal cord mediating the inhibition of FE following repeated genital inflow. Results reveal the nature of the modulatory role that genital afferent information exerts on the expression of FE.

Aphrodisiac properties of Montanoa tomentosa aqueous crude extract in male rats.

Cihuapatli, the Mexican zoapatle (Montanoa tomentosa) has an extensive ethnomedical history of use as a traditional remedy for reproductive impairments. During the study of the ejaculatory function in rats and by testing a set of Mexican plants with medicinal properties, we observed that crude extracts of M. tomentosa facilitated ejaculation. Thus, we decided to analyze the possibility that this plant possessed sexual stimulant properties. To that aim, copulatory behavior of sexually active male rats receiving doses of 38, 75 and 150 mg/kg of the aqueous crude extract of M. tomentosa, as it is prepared in traditional medicine, was assessed. In addition, we evaluated the effect of the 75-mg/kg dose of the extract on males with anesthetization of the genital area and on sexual behavior of sexually inactive male rats (noncopulators). Results showed that acute oral administration of crude extracts of M. tomentosa facilitates expression of sexual behavior in sexually active male rats, significantly increases mounting behavior in genitally anesthetized animals and induces the expression of sexual behavior in noncopulating males. Altogether, these data reveal a facilitatory action of this extract on sexual activity and particularly on sexual arousal. Present findings provide experimental evidence that the crude extract preparation of M. tomentosa, used as a traditional remedy, possesses aphrodisiac properties.

Evidence for changes in brain enkephalin contents associated to male rat sexual activity.

Indirect evidence suggests that ejaculation might activate endogenous opioid systems, which exert an inhibitory influence on male rat sexual behaviour. The objective of the present study was to search for putative long-term changes in the contents of immunoreactive (IR) Met-enkephalin (IR-Met), Leu-enkephalin (IR-Leu) and opioid octapeptide Met--Arg(6)--Gly(7)--Leu(8) (IR-Oct) in specific brain areas, after the execution of different amounts of sexual activity. Additionally, basal contents of these enkephalins were compared between sexually active (SA) and persistent sexually inactive (SI) rats. Immunoreactivity to enkephalins was determined by radioimmunoanalysis, in the frontal cortex, the hypothalamus and midbrain of SA and SI rats, as well as 24 or 48 h after males had one ejaculation or copulated to exhaustion. Twenty-four hours after sexual activity, there was a generalised increase in enkephalin contents that returned to control values at the 48 h measurement in all brain areas, but the hypothalamus, where IR-Met and IR-Oct remained elevated. No differences in the magnitude of the changes were found between rats that ejaculated once and sexually satiated males. IR-Oct concentration in the hypothalamus of SI rats appeared significantly higher than in SA animals, with no differences in IR-Met and IR-Leu. Results give direct evidence of the activation of endogenous opioid systems by male rat sexual activity. The occurrence of long lasting increases in the contents of IR-Met and IR-Oct in the hypothalamus of rats that copulated was detected. Finally, an intrinsically elevated octapeptide concentration in the hypothalamus of SI rats was found.

Cancer genesis: stem tumour cells as an MHC-null/HSP70 - very high 'primordial self' escaping both MHC-restricted and MHC-non- restricted immunesurveillance.

I have previously assumed that in tumours there are stem cells, that owing to the morphophysiologic properties shared with embryonal cells I have defined as 'para-embryonal' cells (PECs). Owing to a blocking mutation, PECs might be able to express only the genic program upstream from the block, but not that downstream. As a consequence, PECs might lack in genic differentiated products, such as MHC molecules, and might be very rich in primitive genic products, such as HSP70 molecules. Like embryonal cells, PECs might carry out induction on adjoining hyperplastic cells, thus transforming them, only phenotypically, into 'differentiated para-embryonal cells' (DPECs), endowed with both MHC and HSP70 molecules. In such a way, nuclei of MHC-non-expressing/HSP70-high expressing stem tumour cells might be surrounded by layers of MHC-expressing/HSP70-expressing non-stem tumour cells. Such a structural tumour organization, actually found by C. Cordon Cardo et al. with regard to the MHC molecule expression, might be responsible for interference phenomena versus the MHC-non-restricted immune cells, such as macrophages and NK cells. So, these cells, the only potentially able to recognize and eliminate MHC-non-expressing stem tumour cells (PECs), might spare them, thus rendering cancer a biological process without any natural immunological solution. Now, I would like to theorically demonstrate that cancer might be a process without immunological solution from the very beginning: the first stem tumour cell might be tolerated as a sort of 'primordial self' because of its MHC-null/HSP70-very high phenotype, recognizable by neither the MHC-restricted nor the MHC-non-restricted immunesurveillance systems of the host. Possible biological roles of HSP70 molecules might account for the immunesurveillance escape of stem tumour cells. Existence of these cells appears to be confirmed by the recent experiments of immunotherapy with autologous tumour-specific HSPs carried out by P. K. Srivastava; moreover, their 'self' nature appears to be confirmed by the most recent experiments of compatible bone marrow allograft carried out by A. M. Carella. On this ground, the main steps for a resolutive antitumour immunotherapy are proposed.