STING-associated vasculopathy with onset in infancy (SAVI) presenting with skin lesions.

STING-associated vasculopathy with onset in infancy (SAVI) is caused by pathogenic gain-of-function variants in the gene TMEM173 (also named stimulator of interferon genes, STING1). This report details the case of an 11-year-old girl with SAVI who presented with skin-limited symptoms and discusses the phenotype-genotype correlations of the TMEM173 variant present in our patient. Treatment of SAVI focuses on preventing the development or progression of organ damage by reducing systemic inflammation. We summarize the available treatments for this syndrome.

Toxicity study in a pig model of intraperitoneal collagenase as an "enzymatic scalpel" directed to break stroma in order to generate a new perspective for peritoneal carcinomatosis approach: an experimental research.

BACKGROUND: This study aimed to measure the toxicity resulting from collagenase administration to the peritoneal cavity in a pig model as a preliminary step to break down the stroma surrounding tumors. METHODS: Eight pigs were treated with 2 different collagenase concentrations previously tested in rats by our group. Time and temperature were controlled using a peritoneal lavage system (PRS System, Combat Medical Ltd.) identical to that used in human surgeries through hyperthermic intraperitoneal chemotherapy (HIPEC); 2 additional pigs were treated with peritoneal lavage only. Samples of blood and peritoneal fluid were collected pre-treatment, immediately after treatment, and 24 h postoperatively. In addition, histological studies and blood collagenase levels were measured. RESULTS: No complications were observed during the surgeries. Intraoperative images evidenced the release of peritoneal tissue during collagenase treatment. After surgery, the animals showed no signs of pain. Diet and mobility were normal at 4 h postoperatively, and there were no significant differences in hematologic or biochemical parameters. Quantification of MMP1 and MMP2 in all samples as measured by absorbance showed no differences in blood collagenase levels between pre-treatment, post-treatment, and 24 h postoperatively. None of the animals treated with collagenase showed peritoneal adhesions during the second surgery. Histologically, peritoneal organs and serous structures did not show any microscopic alterations associated with collagenase treatment in any group. CONCLUSION: Lavage of the peritoneal cavity with doses of up to 100,000 collagen digestion units/animal for 30 min is safe and removes connective tissue from the peritoneal cavity.

Potential of mesenchymal stem cell in stabilization of abdominal aortic aneurysm sac.

BACKGROUND: In their origin, abdominal aortic aneurysms (AAAs) are related to an inflammatory reaction within the aortic wall, which can lead to weakness and degeneration of this structure. One of the most widely accepted treatment modalities for AAAs is the placement of stent grafts. Nevertheless, in some patients blood re-enters the aneurysm sac, creating so-called leaks, which constitute a renewed risk of rupture and death.This study explores the possibility of filling aneurysm sacs treated by endovascular aneurysm repair with adipose tissue-derived mesenchymal stem cells (ASCs) in a porcine model. METHODS: We developed a porcine model using 22 animals by creating an artificial AAA made with a Dacron patch. AAAs were then treated with a coated stent that isolated the aneurysm sac, after which we introduced allogeneic ASC into the sac. Animals were followed-up for up to 3 mo. The experiment consisted of the aforementioned surgical procedure performed first, followed by computed tomography and echo-Doppler imaging during the follow-up, and finally, after sacrificing the animals, histologic analysis of tissue samples from the site of cell implantation by a blinded observer and the detection of implanted cells by immunofluorescence detection of the Y chromosome. RESULTS: Our findings demonstrate the survival of ASCs over the 3 mo after implantation and histologic changes associated with this treatment. Treated animals had less acute and chronic inflammation throughout the study period, and we observed increasing fibrosis of the aneurysm sac, no accumulation of calcium, and a regeneration of elastic fibers in the artery. CONCLUSIONS: The combination of endovascular aneurysm repair and cell therapy on AAAs has promising results for the stabilization of the sac, resulting in the generation of living tissue that can secure the stent graft and even showing some signs of wall regeneration. The therapeutic value of such cell-based therapy will require further investigation.

Lack of habituation of evoked visual potentials in analytic information processing style: evidence in healthy subjects.

Habituation is considered one of the most basic mechanisms of learning. Habituation deficit to several sensory stimulations has been defined as a trait of migraine brain and also observed in other disorders. On the other hand, analytic information processing style is characterized by the habit of continually evaluating stimuli and it has been associated with migraine. We investigated a possible correlation between lack of habituation of evoked visual potentials and analytic cognitive style in healthy subjects. According to Sternberg-Wagner self-assessment inventory, 15 healthy volunteers (HV) with high analytic score and 15 HV with high global score were recruited. Both groups underwent visual evoked potentials recordings after psychological evaluation. We observed significant lack of habituation in analytical individuals compared to global group. In conclusion, a reduced habituation of visual evoked potentials has been observed in analytic subjects. Our results suggest that further research should be undertaken regarding the relationship between analytic cognitive style and lack of habituation in both physiological and pathophysiological conditions.

The influence of total solids content and initial pH on batch biohydrogen production by solid substrate fermentation of agroindustrial wastes.

Hydrogen is a valuable clean energy source, and its production by biological processes is attractive and environmentally sound and friendly. In México 5 million tons/yr of agroindustrial wastes are generated; these residues are rich in fermentable organic matter that can be used for hydrogen production. On the other hand, batch, intermittently vented, solid substrate fermentation of organic waste has attracted interest in the last 10 years. Thus the objective of our work was to determine the effect of initial total solids content and initial pH on H2 production in batch fermentation of a substrate that consisted of a mixture of sugarcane bagasse, pineapple peelings, and waste activated sludge. The experiment was a response surface based on 2(2) factorial with central and axial points with initial TS (15-35%) and initial pH (6.5-7.5) as factors. Fermentation was carried out at 35 °C, with intermittent venting of minireactors and periodic flushing with inert N2 gas. Up to 5 cycles of H2 production were observed; the best treatment in our work showed cumulative H2 productions (ca. 3 mmol H2/gds) with 18% and 6.65 initial TS and pH, respectively. There was a significant effect of TS on production of hydrogen, the latter decreased with initial TS increase from 18% onwards. Cumulative H2 productions achieved in this work were higher than those reported for organic fraction of municipal solid waste (OFMSW) and mixtures of OFMSW and fruit peels waste from fruit juice industry, using the same process. Specific energetic potential due to H2 in our work was attractive and fell in the high side of the range of reported results in the open literature. Batch dark fermentation of agrowastes as practiced in our work could be useful for future biorefineries that generate biohydrogen as a first step and could influence the management of this type of agricultural wastes in México and other countries and regions as well.

Therapeutic effect of adipose-derived mesenchymal stem cells in a porcine model of abdominal sepsis.

BACKGROUND: The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis. METHODS: We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 106 cells/kg or 4 × 106 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity. RESULTS: One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-ß in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity. CONCLUSIONS: Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.

Quantum magnetomechanics with levitating superconducting microspheres.

We show that by magnetically trapping a superconducting microsphere close to a quantum circuit, it is possible to perform ground-state cooling and prepare quantum superpositions of the center-of-mass motion of the microsphere. Due to the absence of clamping losses and time-dependent electromagnetic fields, the mechanical motion of micrometer-sized metallic spheres in the Meissner state is predicted to be very well isolated from the environment. Hence, we propose to combine the technology of magnetic microtraps and superconducting qubits to bring relatively large objects to the quantum regime.

Intraperitoneal collagenase as a novel therapeutic approach in an experimental model of colorectal peritoneal carcinomatosis.

The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently. In this study, we evaluate the safety and efficacy of intraperitoneal collagenase associated or not to mitomycin for treatment of colorectal peritoneal metastases in an experimental rat model. Using a fixed-dose procedure, we found that a dose of collagenase of 37 IU/mL administered for 15 min with a hyperthermia pump at 37.5 °C, both in isolation or associated to sequential treatment with intraperitoneal mitomycin, led to a macroscopic decrease in tumor volume as evaluated by the modified peritoneal cancer index (mPCI). Concerning the safety of the procedure, the animals showed no physiological or behavioral disorders during 8 weeks of follow-up. Local treatment for peritoneal metastases of colorectal origin with intraperitoneal collagenase has proved safe and effective in an experimental murine model. Therefore, the stroma-first approach by enzymatic breakdown of collagen from the tumor's extracellular matrix provides a new therapeutic target for colorectal peritoneal metastases.

Long-term effects of a sensitisation campaign on migraine: the Casilino study.

In 2003, we conducted a sensitisation campaign on migraine in the Casilino district of Rome, by sending a letter with the ID Migraine test to all the households and placing posters in the GPs' waiting room. Out of 195 headache patients recruited, 92% had migraine while 73% had never consulted a physician for headache. The aim of this study was to evaluate the long-term impact of this campaign. The follow-up was performed by a telephone interview. The questionnaire considered the characteristics of headache, quality of life, preventive and acute treatments, drug efficacy, comorbidity and subjective usefulness of the campaign. Of the 179 migraineurs, 90.5% (mean age 40.7 +/- 16.5, 139 females) were included in the follow-up. An improvement was observed in mean pain intensity (-13.9%; p < 0.0001) and mean HIT-6 score (-6.1%; p = 0.0003). The campaign was considered to be useful by 63.6% of cases, while 66.1% reported an improvement in their clinical status. Improved patients showed a decreased mean number of days with headache per month (-51.7%; p < 0.0001), pain intensity (-21.8%; p < 0.0001), headache duration (-18.1%; p = 0.0008)and HIT-6 score (-11.7%; p < 0.0001). Our data suggest that the effects of a "single shot" campaign are beneficial not only in a short-term perspective, but even in the longterm. Moreover, the lack of benefit in more severe cases suggests that such patients should not be treated by GPs alone: patients in whom the HIT-6 score, frequency,severity or duration of headache worsen should be promptly referred to the headache clinic.

Postoperative treatment with phytotheraphy Graminex G63 (CERNILEN-Flogo®) after greenlight laser XPS (180W) photovaporization of the prostate (PVP), can affect patient's quality of life?

OBJECTIVE: Phytotherapic treatment as Cernilen-flogo® is commonly used to treat chronic pelvic pain, chronic prostatitis, and BPE (benign prostatic enlargement). In our study, for the first time, we aim to evaluate postoperatively Cernilen-flogo® therapy in patients with BPE/LUTS (lower urinary tract symptoms) previously treated with Greenlight laser XPS (180W) photovaporization of prostate (PVP) to improve surgical outcomes. MATERIALS AND METHODS: We collected data from patients treated with PVP for BPE/LUTS international prostate symptom score (IPSS) >20 unresponding to conventional treatment. Two groups of patients were analyzed: Group A including 15 patients (50%) treated postoperatively with Cernilen-flogo® vs. no treatment Group B. One expert surgeon performed all the procedures. RESULTS: 30 patients included with BPE/LUTs previously treated with PVP. There was no difference between patients' demographic, median age, prostate volume and PSA (prostate specific antigen) level. All patients had a postoperative evaluation after 30-45 days. Patients with postoperative complications (acute urinary retention, postoperative hematuria) were excluded from our study. All patients had a preoperative and postoperative evaluation of IPSS, bother score (BS) and pelvic discomfort (visual analogic scale VAS). Preoperatively there was no significative difference in IPSS, BS and VAS. IPSS Group A was postoperatively 7.13 (SD 1.64) and Group B was 7.33 (SD 1.58) (p=0.67); BS Group A was postoperatively 1.33 (SD 0.81), Group B was 1.73 (SD 1.09) (p=0.30), and VAS Group A was 2.73 (SD 1.9) and Group B was 4.33 (SD 1.58) (p=0.004) showing a statistically significative difference between the two groups in pelvic discomfort with a better outcome in patients treated with Cernilen-flogo®. CONCLUSIONS: Our study showed that Cernilen-flogo® treatment after PVP is effective and minimize patient's pelvic discomfort showed by lower VAS level resulting in better postoperatively patient's quality of life (QOL).

Experimental confounding factors affecting stability, transport and metabolism of flavanols and hydroxycinnamic acids in Caco-2 cells.

Studying bioavailability of polyphenols is essential to understand the health effects of these compounds. Human epithelial cells are commonly used in intestinal absorption and transport experiments but the changes polyphenols undergo during incubation, due to their chemical instability under the cell culture conditions, are scarcely known and might lead to inaccurate conclusions. Based on abundance of flavanols and hydroxycinnamic acids in the diet, epicatechin, epicatechin-3-gallate and procyanidin B2 as flavanols along with 5-caffeoylquinic and 3,5-dicaffeoylquinic acids as hydroxycinnamic acids were selected to comparatively evaluate their absorption and metabolism using an in vitro Caco-2 cell model. Special emphasis was paid to the structure-stability relationship of these phenolic compounds in Dulbecco's Modified Eagle's Medium (DMEM) under the cell culture conditions. The tested compounds were scarcely absorbed and minimally metabolized by the intestinal epithelium cells. The cell transport study showed prevalent efflux for flavanols opposite to absorption for hydroxycinnamates. Intestinal metabolism revealed that hydroxycinnamates were preferentially hydrolyzed and subsequently methylated, whereas hydrolysis of flavanols could not be confirmed, being mostly conjugated to sulfate, methyl- and methyl-sulfate derivatives. It is noteworthy that methyl derivatives of procyanidin-B2 were detected inside Caco-2 cells, confirming its absorption. In addition, culture medium influenced phenol isomerization to a higher extent than cells. In conclusion, hydroxycinnamates were better absorbed than flavanols although their bioavailability was limited in this intestinal cell model.

Combined pharmacological and short-term psychodynamic psychotherapy for probable medication overuse headache: a pilot study.

We studied the effects of short-term psychodynamic psychotherapy (STPP) and pharmacological therapy in 26 consecutive patients with probable medication overuse headache (pMOH). Patients underwent a standard in-patient detoxification protocol, lasting a mean of 7 days. Eleven patients overused non-steroidal anti-inflammatory drugs (NSAIDs), five a combination of NSAIDs and triptans, four triptans, four a combination of NSAIDs, and three triptans and ergot derivates. Preventive therapy was initiated during detoxification. The STPP protocol comprised the Brief Psychodynamic Investigation (BPI) and psychoanalysis-inspired psychotherapy. All patients (groups A and B) underwent the BPI and pharmacological therapy. Half of the patients (group B) also not randomly underwent psychoanalysis-inspired psychotherapy. We found a significant interaction between time and group for headache frequency and medication intake. At 12-month follow-up, a statistically greater decrease in headache frequency and medication intake was observed in group B than in group A (P = 0.0108 and P = 0.0097, respectively). The relapse rate was much lower in group B patients at both 6 and 12 months [15.3%, odds ratio (OR) 0.11, P = 0.016, and 23%, OR 0.18, P = 0.047, respectively] than in group A. The risk of developing chronic migraine (CM) during follow-up was higher in group A than in group B at 6 (OR 2.0, P = 0.047) and 12 months (OR 2.75, P = 0.005). Our study suggests that STPP in conjunction with drug withdrawal and prophylactic pharmacotherapy relieves headache symptoms in pMOH, reducing both long-term relapses and the burden of CM.

Human infections due to Schizophyllumcommune: Case report and review of the literature.

Schizophyllumcommune is an environmental basidiomycetous fungus, causing occasional, predominantly respiratory, infections in humans. Although S. commune is considered an emerging pathogen, some authors pointed out the possibility that the increase in the diagnosed cases may be also due to recent advances in diagnostic technologies now allowing a more prompt and precise identification at the species level. Here we describe the first Italian case of chronic non-invasive fungal rhinosinusitis due to S. commune in an immunocompetent subject and update the literature review on S. commune sinusitis published between 2012-2019. A timely diagnosis is important to avoid local and systemic complications due to infection with this fungus. In our case, prompt identification at species level was only possible with the use of MALDI-TOF mass spectrometry and confirmed by sequence analysis of ribosomal DNA ITS regions, due to the difficulty in achieving a correct and rapid identification using routine morphological analysis.

Interictal habituation deficit of the nociceptive blink reflex: an endophenotypic marker for presymptomatic migraine?

Habituation of the nociception-specific blink reflex (nBR) is reduced interictally in migraine patients. This could be related to the habituation deficit of evoked cortical responses, a reproducible abnormality in migraine which has a familial character, or to central trigeminal sensitization due to repeated attacks. We compared nBR habituation in healthy volunteers devoid of personal or family history of migraine (HV), in migraine without aura patients (MO) and in healthy volunteers with a family history of migraine in first degree relatives (HV-F). We elicited the nBR by stimulating the right supraorbital region with a custom-built electrode in 16 MO between attacks, 15 HV and 14 HV-F. Habituation was measured as the percentage area-under-the-curve decrease in 10 consecutive blocks of five averaged rectified responses. nBR habituation was clearly reduced in MO and HV-F compared to HV. Percentage area under the curve decreased between the 1st and the 10th block by 55.01% in HV, 25.71% in MO (P = 0.001) and 26.73% in HV-F (P = 0.043). HV-F had the most pronounced abnormality with potentiation instead of habituation in the second block. We found a positive intraindividual correlation between attack frequency and habituation in MO (r = 0.621; P = 0.010). Migraine patients have interictally a deficient habituation of the nBR which is inversely related to attack frequency, suggesting that it is not due to trigeminal sensitization. Surprisingly, the most pronounced habituation deficit is found in asymptomatic individuals with a family history of migraine. Deficient nBR habituation could thus be a trait marker for the genetic predisposition to migraine.

Interictal abnormalities of gamma band activity in visual evoked responses in migraine: an indication of thalamocortical dysrhythmia?

Between attacks, migraineurs lack habituation in standard visual evoked potentials (VEPs). Visual stimuli also evoke high-frequency oscillations in the gamma band range (GBOs, 20-35 Hz) assumed to be generated both at subcortical (early GBOs) and cortical levels (late GBOs). The consecutive peaks of GBOs were analysed regarding amplitude and habituation in six successive blocks of 100 averaged pattern reversal (PR)-VEPs in healthy volunteers and interictally in migraine with (MA) or without aura patients. Amplitude of the two early GBO components in the first PR-VEP block was significantly increased in MA patients. There was a significant habituation deficit of the late GBO peaks in migraineurs. The increased amplitude of early GBOs could be related to the increased interictal visual discomfort reported by patients. We hypothesize that the hypofunctioning serotonergic pathways may cause, in line with the thalamocortical dysrhythmia theory, a functional disconnection of the thalamus leading to decreased intracortical lateral inhibition, which can induce dishabituation.

Acute subcortical stroke and early serotonergic modification: a IDAP study.

The intensity dependence of the auditory-evoked potentials (IDAP) is inversely related to serotonergic tone. Depression is frequently observed after stroke, associated with cognitive impairment and increased mortality. Aim of this study was to investigate the serotonergic tone in acute stroke patients by IDAP. Consecutive patients with an acute stroke admitted in our stroke unit were evaluated using clinical and instrumental examinations and compared with healthy controls. The IDAP was calculated as the linear amplitude/stimulus intensity function (ASF) slope, by measuring the peak-to-peak amplitude of Nl-P2 on four blocks of different stimulus intensities. Twenty patients were enrolled; 11 had a right brain infarction; nine had depressive symptoms (DS). The ASF slope of the auditory-evoked potentials was markedly increased in stroke patients compared with controls (P = 0.021). Stroke patients with DS had a significant steeper ASF slope than controls (P = 0.017). There was no statistical difference in ASF slope between stroke patients without DS and controls. Post-stroke depression pathophysiology is still debated. Our study suggests that in acute stroke patients with DS, there is a direct involvement of the serotonergic system, regardless the degree of disability and the site of the lesion.

Utilidad de la ecografía como método diagnóstico de reflujo ácido patológico en comparación con la pHmetría esofágica / Usefulness of ultrasound as a diagnostic method of pathological acid reflux compared to esophageal pH metry

Introducción: el gold standard para el diagnóstico de reflujo ácido en Pediatría es la pHmetría 24 horas. La ecografía ha demostrado ser una técnica incruenta y existen pocos estudios que la comparen con la pHmetría. Métodos: estudio prospectivo, observacional y analítico. Se realizó estudio ecográfico a pacientes con indicación de pHmetría, y previa a esta. Se determinaron variables ecográficas propuestas por el grupo de ecografía de la SEGHNP (Gomes 1991 modificado), considerando la presencia de reflujo ácido patológico si tenía dos o más parámetros alterados. Resultados: se incluyeron 32 pacientes, 68,8% (n = 22) varones, entre 1 mes y 13 años. Tenían pHmetría patológica el 59,3% (n = 19). El diagnóstico de reflujo por ecografía según lo propuesto por la SEGHNP no se relacionó con el diagnóstico de reflujo ácido por pHmetría (p = 0,169). La ecografía presentó una sensibilidad de 60% y una especificidad del 61,5%, con valor predictivo positivo (VPP) de 70,58% y valor predictivo negativo de 53,3%. Al analizar cada variable ecográfica y compararla con la presencia de reflujo por pHmetría no hubo datos significativos. Sin embargo, un ángulo de Hiss patológico y una longitud del esófago abdominal menor de 1,3 cm se asociaron estadísticamente con reflujo ácido por pHmetría (p = 0,033), obteniendo un VPP, cociente de probabilidad positivo y probabilidad preprueba positiva altos (88,9%; 5,47; 89,1%, respectivamente), con proporción de falsos positivos bajo (7,7%). Conclusión: en nuestra población estudiada, los criterios ecográ9 (AU)ficos propuestos por la SEGHNP no se relacionan con pHmetría patológica, pero si la presencia de un esófago abdominal menor de 1,3 cm junto a un ángulo de Hiss mayor de 110°

Introduction: the gold standard for diagnosis of acid reflux in paediatric patients is 24-hour pH monitoring. Ultrasound is a non-invasive technique and few studies have compared it with pH monitoring.Methods: prospective, observational and analytical study. We performed an ultrasound examination in patients in whom pH monitoring was indicated before performance of the latter test. We analysed the sonographic variables proposed by the Ultrasound Group of the SEGHNP (modified Gomes 1991 criteria), with 2 or more abnormal sonographic parameters indicating the presence of pathological acid reflux.Results: the study included 32 patients, 68.8% (n = 22) male, aged 1 month to 13 years. The results of pH monitoring were pathological in 59.3% (n = 19). We did not find an association between the sonographic diagnosis of reflux according to the criteria proposed by SEGHNP and the diagnosis of reflux based on pH monitoring (p = 0.169). We found a sensitivity of 60% and a specificity of 61.5% with the use of ultrasound, with a positive predictive value (PPV) of 70.58% and a negative predictive value of 53.3%. When we compared each ultrasound variable separately to the presence of reflux determined by pH monitoring, we did not find any significant associations. However, we found a statistically significant association between the combination of an angle of His in the pathological range and an abdominal oesophagus length of less than 1.3 cm on ultrasound and the detection of acid reflux by pH monitoring (p = 0.033), with a high PPV, positive likelihood ratio and pre-test probability (88.9%, 5.47 and 89.1%, respectively) and a low false-positive rate (7.7%).Conclusion: in our sample, we did not find an association between the... (AU)

Role of silodosin in patients with LUTS/BPE non responding to medical treatment with tamsulosin: a prospective, open-label, pilot study.

OBJECTIVE: Lower urinary tract symptoms (LUTS) are frequently experienced in association with benign prostatic enlargement (BPE). Current guidelines state that alpha-blockers should be considered the first-line therapy of LUTS associated with BPE in most patients. However, in clinical practice treatment efficacy differs among individuals and, therefore, intra-class switch from one alpha-blocker to another, is frequently applied. In particular, switching to silodosin in clinical practice appears an intriguing therapeutic strategy due to the peculiar pharmacological properties of this molecule. This study evaluates the efficacy of silodosin in patients with LUTS associated with BPE who were not-responders to tamsulosin. PATIENTS AND METHODS: This was a prospective, open-label, single-center study. Patients treated with tamsulosin 0.4 mg once daily for BPE/LUTS for at least 12 months and not responding to therapy were switched to silodosin 8 mg once daily. The co-primary endpoints for evaluation of efficacy were the change in IPSS and quality of life (QoL) from the beginning of silodosin therapy to week 8. RESULTS: In total, 96 patients were enrolled. Mean International Prostatic Symptoms Score (IPSS) score at baseline was 20.0 ± 4.4, and it significantly decreased to 18.6 ± 4.5 at week 8 (mean change: -1.3 ± 1.4; 95% CI -1.6 - -1.0; p < 0.03). A decrease was also observed for the two IPSS subscores; in particular, the IPSS subscore for storage symptoms was significantly reduced at week 8, compared with baseline. A significant improvement in QoL was observed after switching to silodosin, as compared with baseline (-0.8 ± 1.0; 95% CI -1.0 - -0.6; p < 0.001). CONCLUSIONS: Silodosin improves IPSS symptoms score and QoL in patients with LUTS associated with BPE who were not-responders to tamsulosin therapy.

Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action.

We enrolled six patients suffering from refractory chronic cluster headache in a pilot trial of neurostimulation of the ipsilateral ventroposterior hypothalamus using the stereotactic coordinates published previously. After the varying durations needed to determine optimal stimulation parameters and a mean follow-up of 14.5 months, the clinical outcome is excellent in three patients (two are pain-free; one has fewer than three attacks per month), but unsatisfactory in one patient, who only has had transient remissions. Mean voltage is 3.28 V, diplopia being the major factor limiting its increase. When the stimulator was switched off in one pain-free patient, attacks resumed after 3 months until it was turned on again. In one patient the implantation procedure had to be interrupted because of a panic attack with autonomic disturbances. Another patient died from an intracerebral haemorrhage that developed along the lead tract several hours after surgery; there were no other vascular changes on post-mortem examination. After 1 month, the hypothalamic stimulation induced resistance against the attack-triggering agent nitroglycerin and tended to increase pain thresholds at extracephalic, but not at cephalic, sites. It had no detectable effect on neurohypophyseal hormones or melatonin excretion. We conclude that hypothalamic stimulation has remarkable efficacy in most, but not all, patients with treatment-resistant chronic cluster headache. Its efficacy is not due to a simple analgesic effect or to hormonal changes. Intracerebral haemorrhage cannot be neglected in the risk evaluation of the procedure. Whether it might be more prevalent than in deep-brain stimulation for movement disorders remains to be determined.

Distribution and inventories of fallout radionuclides (239+240Pu, 137Cs) and 210Pb to study the filling velocity of salt marshes in Doñana National Park (Spain).

Within an extensive multinational and multidisciplinary project carried out in Doñana National Park (Spain) to investigate its preservation and regeneration, the filling velocity of the salt marshes has been evaluated through the calculation of their average sediment accumulation rates. (239+240)Pu and (137)Cs from weapons testing fallout and total (210)Pb distribution profiles and inventories have been determined in some of the most characteristic zones of the park, namely, the ponds (or "lucios") and the waterjets (or "caños"). Plutonium inventories range from 16 to 101 Bq m(-2), (137)Cs values fluctuate between 514 and 3,758 Bq m(-2) and unsupported (210)Pb values comprise between 124 and 9398 Bq m(-2). Average sedimentation rates range from 3 to 5 mm y(-1) (1952-2002). These data are higher than those obtained by carbon dating for the period 6,500 AD-present, estimated as 1.5-2 mm y(-1), suggesting an increase in the accumulation of sediments and the alteration of the park's hydrodynamics caused by the re-channeling of the major rivers feeding the salt marshes.