The role of the Ventral Nucleus of the Trapezoid Body in the auditory prepulse inhibition of the acoustic startle reflex.

Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the ISI of 50 ms, the OCB-lesioned group exhibited a significant increase in%PPI (p < 0.01), which did not occur in the OCB/VNTB-lesioned group. Therefore, the ablation of cholinergic non-olivocochlear neurons in the OCB/VNTB-lesioned group suggests that these neurons contribute to the mediation of auditory PPI at the 50 ms ISI through their cholinergic projections to CRNs. Our study strongly reinforces the notion that auditory PPI encompasses a complex mechanism of top-down cholinergic modulation, effectively attenuating the ASR across different interstimulus intervals within multiple pathways.

Lung optimized treatment with CyberKnife® in inoperable lung cancer patients: feasibility analysis of a mono-institutional 115 patient series.

CyberKnife® Lung Optimized Treatment (LOT) allows the treatment of lung cancer without invasive fiducial implantation. The aim of this retrospective analysis was to evaluate the feasibility, toxicity and clinical outcome. One hundred fifteen patients (124 lesions) were treated with CyberKnife® using LOT. The median age was 72.6 years (range 31.8-90.3). From 124 treated lesions, 52 were with histopathological confirmation (41 primitive pulmonary cancers, 8 pulmonary metastases) and 72 as untyped tumors. For 5 patients (6 lesions) treatment was an in-field re-irradiation. Concomitant therapy was administered in 7 patients. Zero-View tracking was applied in 69 patients, 1-View in 33 patients, 2-View in 22 patients. The median total dose was 45 Gy (range 18-54), median dose/fraction was 15 Gy (range 4-18) with a median prescription isodose of 80% (range 68-85). The median planning target volume (PTV) was 25 cm3 (range 3-195). The median follow-up was 20 months (range 7-47). Thirty-seven patients (32%) were alive with no evidence of disease, 39 patients (34%) were alive with clinically evident disease, and 38 patients (33%) died of the disease. The 1- and 2-year overall survival (OS) rate was 83% and 61%. The median time to progression was 19 months (95% confidence interval: 11-19 months), 1- and 2-year progression-free survival (PFS) rates were 62% and 41%, respectively. Smaller PTV was significantly associated with better OS, PFS and in-field PFS in univariate and multivariate analyses. Acute toxicity was observed in 36 patients (41%). Late toxicity was registered in 25 patients (29%). G3 late toxicity was observed in one patient (1.1%). Our data suggest that fiducial less-stereotactic body radiation therapy (SBRT) is a feasible, well-tolerated and potentially effective treatment with high compliance in the setting of inoperable patients due to concomitant disease or previous treatments.

Periendoscopic management of antiplatelet therapy: Prospective evaluation of adherence to guidelines / Manejo perioendoscópico del tratamiento antiagregante plaquetario: evaluación prospectiva del cumplimiento de las guías clínicas

Introducción: Adherence to guidelines on the periendoscopic management of antiplatelet therapy (APT) has not been analyzed in detail. Our aim was to assess adherence to guidelines in patients referred to our Endoscopy Unit on a case-by-case basis, describing in detail the detected deviations and identifying areas of improvement. Patients and methods: Cross-sectional study of outpatients consecutively scheduled for an unsedated upper or lower gastrointestinal endoscopy between January and June 2015. Patients on anticoagulant therapy were excluded. Results: 675 patients were evaluated, including 91 (13.5%) patients on APT [upper GI endoscopy 25 (27.5%), lower GI endoscopy 66 (72.5%)]. Contrary to the clinical guidelines, aspirin was discontinued in 25 of the 77 patients previously prescribed the drug (32.5%) but this modification was patient's own decision in 11 cases. Most of the apparent deviations in the management of clopidogrel and dual antiplatelet therapy (DAPT) were not true non-adherence cases. The Primary Care physician modified an APT prescribed by another physician in 8 of 9 cases (88.9%), always in cases with aspirin. No relationship was found between the endoscopic procedure's predicted risk of bleeding or the patient's thrombotic risk and modification of therapy. Discussion: In many patients, the peri-procedural management of APT goes against current guidelines, but some of these inconsistencies cannot be considered true deviations from practice. Identified areas for improvement are increasing patient awareness about APT, disseminating the guidelines in Primary Care, and underscoring the significance of thrombotic risk related to APT withdrawal

Introducción: El cumplimiento de las guías clínicas sobre el manejo periendoscópico del tratamiento antiagregante plaquetario (TAP) no se ha analizado con detalle. Nuestro objetivo fue analizar caso por caso el cumplimiento de las guías en los pacientes que acuden a nuestra Unidad de Endoscopia, describiendo con detalle las desviaciones detectadas e identificando áreas de mejora. Pacientes y métodos: Estudio transversal sobre pacientes consecutivos programados para gastroscopia o colonoscopia realizadas sin sedación entre enero y junio de 2015. Se excluyeron los pacientes en tratamiento anticoagulante. Resultados: Se evaluaron 675 pacientes de los que se incluyeron 91 (13,5%) por estar en tratamiento con antiagregante plaquetario (gastroscopias 25 [27,5%], colonoscopias 66 [72,5%]). La aspirina se interrumpió contrariamente a las guías clínicas en 25 de los 77 pacientes que la llevaban (32,5%), pero esta modificación fue una decisión del propio paciente en 11 casos. Muchas de las aparentes desviaciones en el manejo del clopidogrel y del tratamiento antiagregante plaquetario doble (TAPD) no eran verdaderos casos de no cumplimiento. El médico de Atención Primaria modificó el TAP prescrito por otro especialista en 8 de 9 casos (88,9%), siempre en casos de aspirina. No se encontró relación entre el riesgo de sangrado del procedimiento endoscópico o el riesgo de trombosis del paciente y la modificación del tratamiento. Discusión: En una proporción significativa de pacientes el manejo periprocedimiento del TAP va en contra de las guías clínicas, pero algunas de estas desviaciones no pueden considerarse verdaderos incumplimientos. Áreas de mejora son aumentar la información al paciente sobre el TAP, extender la diseminación de las guías a atención primaria y resaltar la importancia del riesgo trombótico relacionado con la suspensión del TAP

Stereotactic radiation therapy in oligometastatic colorectal cancer: outcome of 102 patients and 150 lesions.

To evaluate the local control (LC), progression free survival (PFS), out-field PFS, overall survival (OS), toxicity and failure predictors of SRT in a series of various sites oligometastatic CRC patients. Patients with oligometastatic CRC disease were analyzed retrospectively. The SRT prescribed dose was dependent on the lesion volume and its location. 102 consecutive oligometastatic CRC patients (150 lesions) were included. They underwent SRT between 2012 and 2015. Median prescription dose was 45 Gy (median dose/fraction was 15 Gy/3 fractions biological equivalent dose (BED10) 112.5 Gy). Median follow-up was 11.4 months. No patients experienced G3 and G4 toxicity. No progression was found in 82% (radiological response at 3 months) and 85% (best radiological response) out of 150 evaluable lesions. At 1 and 2 years: LC was 70% and 55%; OS was 90% and 90%; PFS was 37% and 27%; out-field PFS was 37% and 23% respectively. Progressive disease was correlated with BED10 (better LC when BED10 was ≥ 75 Gy (p < 0.0001)). In multivariate analysis, LC was higher in lesions with a Plpnning target volume (PTV) volume < 42 cm3 and BED10 ≥ 75 Gy. Patients with Karnofsky performance status < 90 showed higher out-field progression. SRT is an effective treatment for patients with oligometastases from CRC. Its low treatment-associated morbidity and acceptable LC make of SRT an option not only in selected cases. Further studies should be focused to clarify which patient subgroup will benefit most from this treatment modality and to define the optimal dose to improve LC while maintaining low toxicity profile.

Periendoscopic management of antiplatelet therapy: Prospective evaluation of adherence to guidelines.

INTRODUCCIóN: Adherence to guidelines on the periendoscopic management of antiplatelet therapy (APT) has not been analyzed in detail. Our aim was to assess adherence to guidelines in patients referred to our Endoscopy Unit on a case-by-case basis, describing in detail the detected deviations and identifying areas of improvement. PATIENTS AND METHODS: Cross-sectional study of outpatients consecutively scheduled for an unsedated upper or lower gastrointestinal endoscopy between January and June 2015. Patients on anticoagulant therapy were excluded. RESULTS: 675 patients were evaluated, including 91 (13.5%) patients on APT [upper GI endoscopy 25 (27.5%), lower GI endoscopy 66 (72.5%)]. Contrary to the clinical guidelines, aspirin was discontinued in 25 of the 77 patients previously prescribed the drug (32.5%) but this modification was patient's own decision in 11 cases. Most of the apparent deviations in the management of clopidogrel and dual antiplatelet therapy (DAPT) were not true non-adherence cases. The Primary Care physician modified an APT prescribed by another physician in 8 of 9 cases (88.9%), always in cases with aspirin. No relationship was found between the endoscopic procedure's predicted risk of bleeding or the patient's thrombotic risk and modification of therapy. DISCUSSION: In many patients, the peri-procedural management of APT goes against current guidelines, but some of these inconsistencies cannot be considered true deviations from practice. Identified areas for improvement are increasing patient awareness about APT, disseminating the guidelines in Primary Care, and underscoring the significance of thrombotic risk related to APT withdrawal.

Influence of age, body mass index and comorbidity on major outcomes in acute pancreatitis, a prospective nation-wide multicentre study.

BACKGROUND: There are few large prospective cohort studies evaluating predictors of outcomes in acute pancreatitis. OBJECTIVES: The purpose of this study was to determine the role of age and co-morbid disease in predicting major outcomes in acute pancreatitis. METHODS: Data points were collected according to a predefined electronic data collection form. Acute pancreatitis and its complications were defined according to the revised Atlanta classification. Univariable and multivariable analyses were conducted using Cox proportional hazard regression and multiple logistic regression. RESULTS: From June 2013-February 2015, 1655 adult patients were recruited from 23 centres across Spain. Co-morbid disease, obesity, open surgical necrosectomy within 30 days, and pancreatic necrosis were independently associated with both 30-day mortality and persistent organ failure (p < 0.05 for all). Age was not associated with persistent organ failure, however the extreme of age (>85 years) was associated with mortality (p < 0.05). Co-morbid disease and obesity were not independently associated with a prolonged length of stay or other markers of morbidity on adjusted analysis (p > 0.05). CONCLUSION: Comorbidity and obesity are important determinates of mortality and persistent organ failure in acute pancreatitis, but in the absence of organ failure they do not appear to independently contribute to morbidity. This has important implications for severity classification and predictive models of severity in acute pancreatitis.

Pre Frail 80: Multifactorial Intervention to Prevent Progression of Pre-Frailty to Frailty in the Elderly.

OBJECTIVES: Preventing or delaying frailty has important benefits in the elderly, and in health and social services. Studies have demonstrated the effectiveness of multifactorial interventions in the frail elderly, but there are fewer studies on community-dwelling pre-frail individuals. Identifying pre-frail individuals susceptible to intervention could prevent or delay frailty and its consequences and associated disability and might reverse the state from pre-frail to robust. To evaluate a multifactorial, interdisciplinary primary care intervention in community-dwelling pre-frail elderly patients aged ≥ 80 years. DESIGN: Randomized clinical trial in a Barcelona primary healthcare centre. SETTING: We included 200 community-dwelling subjects aged ≥ 80 years meeting the Fried pre-frailty criteria. Participants were randomized to intervention and control groups. INTERVENTION: The intervention group received a 6-month interdisciplinary intervention based on physical exercise, Mediterranean diet advice, assessment of inadequate prescribing in polypharmacy patients and social assessment, while the control group received standard primary healthcare treatment. RESULTS: 173 pre-frail participants (86.5%) completed the study; mean age 84.5 years, 64.5% female. At twelve months, frailty was lower in the intervention group (RR 2.90; 95%CI 1.45 to 8.69). Reversion to robustness was greater in the intervention group (14.1% vs.1.1%, p <0.001). Functional and nutritional status, adherence to Mediterranean diet, quality of life, and functional mobility were improved in the intervention group (p ≤0.001). CONCLUSION: A multifactorial, interdisciplinary primary healthcare intervention focused on physical exercise, nutrition, review of polypharmacy and social assessment prevented frailty in pre-frail elderly patients, and improved functional capacity, quality of life and adherence to the Mediterranean diet.

Adsorptive granulocyte/monocyte apheresis use in severe ulcerative colitis and determination of changes in plasma cytokines.

Despite controversy regarding the use of granulocyte/monocyte adsorption (GMA) in inflammatory bowel disease, some studies have shown favorable outcomes when it is used in steroid-dependent patients with ulcerative colitis (UC). The mechanisms responsible for such outcomes are not well characterized, but changes in immune cell populations and cytokine levels have been suggested to play an important role. We report the cases of 3 patients with chronically active severe UC who underwent GMA due to an inadequate response to standard and rescue therapy, as well as changes to their plasma cytokine profile. All the patients presented severe UC that was only partially responsive to various immunosuppressive drugs, and they were, therefore, referred for colectomy; however, all 3 refused this option, which led to the compassionate use of GMA as a last therapeutic resort. Following GMA treatment, rapid normalization of the clinical, endoscopic and laboratory parameters was observed in all the patients. Despite having achieved a good response, most cytokines remained at high concentrations after GMA, and only two, IL-6 and IL-8, showed a clear decrease throughout the GMA sessions. In view of this outcome, we hypothesize that GMA can help to lower the inflammatory load, thereby enhancing the effect of biologic drugs. To confirm this hypothesis and explore further indications for GMA, we propose the need for research directed toward the characterization of immune cell populations and their specific cytokine production rather than global cytokine assessment.

O2 selective membranes based on a dextrin-nanosponge (NS) in a PVDF-HFP polymer matrix for Li-air cells.

A novel oxygen selective highly hydrophobic membrane is prepared by non-solvent induced phase separation in which a dextrin-based nanosponge is incorporated into a poly(vinylidene fluoride co-hexafluoropropylene) (PVDF-HFP) matrix. The membrane presents high capability to entrap moisture from air as well as good hydrophobic behaviour. The membrane was assembled in a pouch type Li-air cell, which was cycled in a galvanostatic mode at curtailed capacity, in air with 17% relative humidity (RH). Owing to the protection of the membrane, the Li-air cell was able to discharge and re-charge for approximately 145 cycles, which correspond to about 1450 h of cell operation.

Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis.

 Background and aims. Steroid-related hepatotoxicity has become one of the most relevant causes of drug induced liver cholestasis. Some patients do not improve after standard medical treatment (SMT) and may therefore require other approaches, like extracorporeal liver support. MATERIAL AND METHODS: We report four cases of patients with pruritus, abnormal liver function tests and biopsy-proven anabolic steroid-induced cholestasis who were unresponsive to SMT. They underwent treatment with albumin dialysis (Molecular Adsorbent Recirculating System -MARS®-). A minimum of two MARS sessions were performed. RESULTS: After MARS® procedure, patients' symptoms improved, as well as liver function tests, thus avoiding liver transplantation. CONCLUSION: Albumin dialysis appears as a valuable therapeutic option for the management of anabolic steroid-induced cholestasis in patients that are unresponsive to SMT.

Appearance of a reservoir of hookworm-related cutaneous larva migrans in Brittany?

We describe two cases of hookworm-related cutaneous larva migrans acquired in Brittany (North-Western France). The patients were a 23-year-old woman and a 28-year-old man. In both patients the feet were involved. In the second patient, a superinfection due to Staphylococcus aureus was recorded. The appearance in Brittany of a reservoir of nematodes capable of causing hookworm-related cutaneous larva migrans is hypothesized.

Localization and hormonal regulation of endometrial matrix metalloproteinase-26 in the rhesus macaque.

BACKGROUND: The current understanding of hormonal regulation of matrix metalloproteinase-26 (MMP-26) in the primate endometrium is incomplete. The goal of this work was to clarify estrogen and progesterone regulation of MMP-26 in the endometrium of ovariectomized, hormone-treated rhesus macaques. METHODS: Ovariectomized rhesus macaques (n= 66) were treated with estradiol (E(2)), E(2) plus progesterone, E(2) followed by progesterone alone or no hormone. Endometrium was collected from the hormone-treated animals during the early, mid- and late proliferative and secretory phases of the artificial menstrual cycle. MMP-26 expression was quantified by real-time PCR, and MMP-26 transcript and protein were localized by in situ hybridization and immunohistochemistry and correlated with estrogen receptor 1 and progesterone receptor (PGR). RESULTS: MMP-26 was localized to glandular epithelium and was undetectable in the endometrial stroma and vasculature. MMP-26 transcript levels were minimal in the hormone-deprived macaques and treatment with E(2) alone did not affect MMP-26 levels. Treatment with progesterone both in the presence and absence of E(2) stimulated MMP-26 expression in the early and mid-secretory phases (P < 0.001). MMP-26 expression preceded decidualization of endometrial stroma. MMP-26 levels then declined to baseline in the late secretory phase (P < 0.01) despite continued E(2) plus progesterone treatment. Loss of detectable MMP-26 expression in the late secretory phase was correlated with late secretory phase loss of glandular epithelial PGR. CONCLUSIONS: Endometrial MMP-26 expression is dependent on the presence of progesterone in the early secretory phase and then gradually becomes refractory to progesterone stimulation in the late secretory phase. In the macaque, MMP-26 is a marker of the pre-decidual, secretory endometrium. During the second half of the late secretory phase, and during decidualization, MMP-26 loses its response to progesterone concurrent with the loss of epithelial PGR. The decline in MMP-26 levels between the mid- and late secretory phases may play a role in the receptive window for embryo implantation.

IGFR-I expression and structural analysis of the hard palatine mucosa in an ethanol-drinking rat strain (UChA and UChB).

The study analyzed the effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the hard palatine mucosa of rats UChA and UChB (lines with voluntary alcohol consumption) in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the digestive system. Thirty female adult animals aged 120 days were divided into three experimental groups. (1) Ten UChA rats (genetically low ethanol consumer) with voluntary intake of 10% v/v (5.45 g/kg/day) ethanol solution and water. (2) Ten UChB (genetically high ethanol consumer) rats with voluntary intake of 10% v/v (7.16 g/kg/day) ethanol solution and water. (3) Ten Wistar rats with voluntary ad libitum water intake (control group). Both groups received Nuvital pellets ad libitum. The IGFR-I expression was intense in both experimental groups. The epithelial cells of the alcoholic rats UChA and UChB showed many alterations such as the presence of lipid droplets, altered nuclei, nuclei in corneum layer and disrupted mitochondria. It was concluded that ethanol intake induces ultrastructural lesions in the hard palatine mucosa.

Cutaneous myiasis caused by Dermatobia hominis acquired in Jamaica / Miasis cutánea causada por Dermatobia Hominis acquirida en Jamaica

The authors describe a case of cutaneous myiasis caused by Dermatobia hominis in a 23-year old Italian woman who contracted the infestation during a tour in Jamaica. The infestation was located on the back and was characterized clinically by a single inflammatory nodule. To our knowledge, this is the first case of cutaneous myiasis due to Dermatobia hominis acquired in Jamaica.

Los autores describen un caso de miasis cutánea causada por Dermatobia hominis en una mujer italiana de 23 años, quien contrajo la infestación durante una gira en Jamaica. La infestación estaba localizada en la espalda y se caracterizaba clínicamente por un nódulo inflamatorio. Hasta donde sabemos, éste es el primer caso de miasis cutánea por Dermatobia hominis adquirida en Jamaica.

[Splenic congenital cysts as incidental finding during emergency sonography: differential diagnostic and therapeutic indications. Case report]. / Le cisti spleniche congenite come reperto accessorio di ecografia in urgenza: criteri di diagnosi differenziale e principi di trattamento. Case report.

Splenic cysts are occasionally discovered during instrumental investigations performed for other reasons. Clinical exam is in fact negative in presence of the non complicated small lesions, such those ones identified with sonography in a young man, controlled in our Emergency Unit for car crash. Anamnestic report and clinical evaluation have supported congenital etiology of focal lesions, observed in kidneys too, confirming the polydistrectuality of the abnormality, which must be only periodically controlled, if it's not complicated.

Cutaneous myiasis caused by Dermatobia hominis acquired in Jamaica.

The authors describe a case of cutaneous myiasis caused by Dermatobia hominis in a 23-year-old Italian woman who contracted the infestation during a tour in Jamaica. The infestation was located on the back and was characterized clinically by a single inflammatory nodule. To our knowledge, this is the first case of cutaneous myiasis due to Dermatobia hominis acquired in Jamaica.

[How to implement a unique triage system in the emergency departments of Latium, Italy]. / Come implementare un modello di Triage di pronto soccorso. L'esperienza della regione Lazio.

Triage is an efficient system that emergency departments (EDs) use to sort out presenting patients on the basis of the speed with which they need treatment. Because triage is not used consistently in the EDs of Latium, a region in central Italy, the regional Public Health Agency (PHA) planned and implemented a regional model of triage in all EDs. This manuscript describe the regional implementation strategy. The PHA activated the "Regional Triage Program--RTP" including: development and testing of a "triage section" in the computerized EDs clinical chart; production of an operational handbook for the RTP for triage health professionals (HPs); implementation of an continuum educational program on the "RTP" in all EDs of Latium. The computerized triage section was tested and implemented in all EDs in the region. The handbook for triage HPs was produced. The educational program, has been ongoing since 2008 in all regional EDs. Selected HPs, identified as "facilitators", were trained on how to implement the RTP. They will organize, in their own EDs, small groups of nurses to conduct on-site training of the RTP. The RTP was received with enthusiasm by most HPs, however its introduction into current practice could be hampered by organizational/structural problems and conflicts between nurses and doctors. Next actions of the regional program will be to overcome the possible above mentioned troubles.