Ultra-slow mechanical stimulation of olfactory epithelium modulates consciousness by slowing cerebral rhythms in humans.

The coupling between respiration and neural activity within olfactory areas and hippocampus has recently been unambiguously demonstrated, its neurophysiological basis sustained by the well-assessed mechanical sensitivity of the olfactory epithelium. We herein hypothesize that this coupling reverberates to the whole brain, possibly modulating the subject's behavior and state of consciousness. The olfactory epithelium of 12 healthy subjects was stimulated with periodical odorless air-delivery (frequency 0.05 Hz, 8 s on, 12 off). Cortical electrical activity (High Density-EEG) and perceived state of consciousness have been studied. The stimulation induced i) an enhancement of delta-theta EEG activity over the whole cortex mainly involving the Limbic System and Default Mode Network structures, ii) a reversal of the overall information flow directionality from wake-like postero-anterior to NREM sleep-like antero-posterior, iii) the perception of having experienced an Altered State of Consciousness. These findings could shed further light via a neurophenomenological approach on the links between respiration, cerebral activity and subjective experience, suggesting a plausible neurophysiological basis for interpreting altered states of consciousness induced by respiration-based meditative practices.

The clinical value of magnetic resonance defecography in males with obstructed defecation syndrome.

BACKGROUND: The aim of the present study was to assess the relationship between symptoms of obstructed defecation and findings on magnetic resonance (MR) defecography in males with obstructed defecation syndrome (ODS). METHODS: Thirty-six males with ODS who underwent MR defecography at our institution between March 2013 and February 2016 were asked in a telephone interview about their symptoms and subsequent treatment, either medical or surgical. Patients were divided into 2 groups, one with anismus (Group 1) and one with prolapse without anismus (Group 2). The interaction between ODS type and symptoms with MR findings was assessed by multivariate analysis for categorical data using a hierarchical log-linear model. MR imaging findings included lateral and/or posterior rectocele, rectal prolapse, intussusception, ballooning of levator hiatus with impingement of pelvic organs and dyskinetic puborectalis muscle. RESULTS: There were 21 males with ODS due to anismus (Group 1) and 15 with ODS due to rectal prolapse/intussusception (Group 2). Mean age of the entire group was 53.6 ± 4.1 years (range 18-77 years). Patients in Group 1 were slightly older than those in Group 2 (age peak, sixth decade in 47.6 vs 20.0%, p < 0.05). Symptoms most frequently associated with Group 1 patients included small volume and hard feces (85.0%, p < 0.01), excessive strain at stool (81.0%, p < 0.05), tenesmus and fecaloma formation (57.1 and 42.9%, p < 0.05); symptoms most frequently associated with Group 2 patients included mucous discharge, rectal bleeding and pain (86.7%, p < 0.05), prolonged toilet time (73.3%, p < 0.05), fragmented evacuation with or without digitation (66.7%, p < 0.005). Voiding outflow obstruction was more frequent in Group 1 (19.0 vs 13.3%; p < 0.05), while non-bacterial prostatitis and sexual dysfunction prevailed in Group 2 (26.7 and 46.7%, p < 0.05). At MR defecography, two major categories of findings were detected: a dyskinetic pattern (Type 1), seen in all Group 1 patients, which was characterized by non-relaxing puborectalis muscle, sand-glass configuration of the anorectum, poor emptying rate, limited pelvic floor descent and final residue ≥ 2/3; and a prolapsing pattern (Type 2), seen in all Group 2 patients, which was characterized by rectal prolapse/intussusception, ballooning of the levator hiatus with impingement of the rectal floor and prostatic base, excessive pelvic floor descent and residue ≤ 1/2. Posterolateral outpouching defined as perineal hernia was present in 28.6% of patients in Group 1 and were absent in Group 2. The average levator plate angle on straining differed significantly in the two patterns (21.3° ± 4.1 in Group 1 vs 65.6° ± 8.1 in Group 2; p < 0.05). Responses to the phone interview were obtained from 31 patients (18 of Group 1 and 13 of Group 2, response rate, 86.1%). Patients of Group 1 were always treated without surgery (i.e., biofeedback, dietary regimen, laxatives and/or enemas) which resulted in symptomatic improvement in 12/18 cases (66.6%). Of the patients in Group 2, 2/13 (15.3) underwent surgical repair, consisting of stapled transanal rectal resection (STARR) which resulted in symptom recurrence after 6 months and laparoscopic ventral rectopexy which resulted in symptom improvement. The other 11 patients of Group 2 were treated without surgery with symptoms improvement in 3 (27.3%). CONCLUSIONS: The appearance of various abnormalities at MR defecography in men with ODS shows 2 distinct patterns which may have potential relevance for treatment planning, whether conservative or surgical.

Cryptic and rare Aspergillus species in Brazil: prevalence in clinical samples and in vitro susceptibility to triazoles.

Aspergillus spp. are among the most common causes of opportunistic invasive fungal infections in tertiary care hospitals. Little is known about the prevalence and in vitro susceptibility of Aspergillus species in Latin America, because there are few medical centers able to perform accurate identification at the species level. The purpose of this study was to analyze the distribution of cryptic and rare Aspergillus species among clinical samples from 133 patients with suspected aspergillosis admitted in 12 medical centers in Brazil and to analyze the in vitro activity of different antifungal drugs. The identification of Aspergillus species was performed based on a polyphasic approach, as well as sequencing analysis of the internal transcribed spacer (ITS) region, calmodulin, and ß-tubulin genes and phylogenetic analysis when necessary. The in vitro susceptibility tests with voriconazole, posaconazole, and itraconazole were performed according to the CLSI M38-A2 document (2008). We demonstrated a high prevalence of cryptic species causing human infection. Only three isolates, representing the species Aspergillus thermomutatus, A. ochraceus, and A. calidoustus, showed less in vitro susceptibility to at least one of the triazoles tested. Accurate identifications of Aspergillus at the species level and with in vitro susceptibility tests are important because some species may present unique resistance patterns against specific antifungal drugs.

Metacognitive beliefs relate specifically to sleep quality in primary insomnia: a pilot study.

OBJECTIVE: To identify whether metacognitive aspects are a specific mental pattern of primary insomnia (PI) or an aspecific correlate of sleep alterations. METHODS: Sleep quality (Pittsburgh Sleep Quality Index: PSQI), anxiety (Self-rating Anxiety State: SAS), depression (Beck Depression Inventory: BDI) and metacognition (Metacognitions Questionnaire - Insomnia: MCQ-I) were evaluated in 24 PI patients, 13 snorers and 17 healthy controls. Rank-transformed PSQI, BDI, SAS and MCQ-I scores were submitted to one-way analysis of variance with group as a between-factor. PSQI was submitted to three-way analysis of covariance (ANCOVA) with MCQ-I, BDI or SAS as covariate and group as a between-factor. Post-hoc analyses were conducted using pairwise comparisons with Sidak correction. RESULTS: As expected, PSQI scores significantly differentiated the three groups, one from another: PI had highest scores followed by snorers and healthy controls. PI subjects had MCQ-I scores significantly higher than those of snorers and healthy controls; no difference between the latter groups was found. The ANCOVA on PSQI with MCQ-I as a covariate abolished the difference in sleep quality between PI and snorers, whereas covarying for BDI or SAS left the differences in sleep quality between the groups unchanged. CONCLUSION: These preliminary results lead to two main conclusions: (i) metacognitive aspects are more prominent in PI when compared to snorers and healthy controls; (ii) MCQI shows higher sensitivity in defining PI patients, with respect to PSQI. If these findings are confirmed and expanded by further studies, the development of a specific metacognitive model of primary insomnia may be warranted.

A survey on virtual environment applications to fear of public speaking.

BACKGROUND: Social Anxiety Disorder (SAD) is one of the most prevalent anxiety disorders in Europe and comprises the fear of public speaking as its typical sub-type. Cognitive-Behavioural Therapy (CBT) is the intervention of choice for SAD, and it includes exposure to anxiety-provoking stimuli to induce systematic desensitization and reduce anxiety. Similarly, exposure therapy per se has been used and found effective, although it is not as specific as CBT for the treatment of SAD. Interestingly, exposure to anxiety-provoking situations can be achieved in Virtual Environments (VEs) through the simulation of social situations allowing individuals with public speaking anxiety to live and develop real exposure-like reactions. The Virtual Reality Exposure Therapy (VRET) is the treatment of anxiety disorders based on such VEs. AIM: This article aims to provide an overview of the scientific literature related to the applications of Virtual Reality to the treatment of fear of public speaking. MATERIALS AND METHODS: We conducted the literature review on PubMed and Google Scholar for studies including the fear-of-public-speaking VEs. RESULTS AND CONCLUSIONS: Reviewed studies addressed two main aspects: the design parameters of the VEs for adequate reactions to synthetic social stimuli, and the efficacy of VEs for fear of public speaking treatment. VEs resulted effective for triggering as-if-real reactions in relation to public speaking. VE-based exposures reduced public speaking anxiety measurements, decreased scores and maintained them at 3 month follow-up. Studies comparing VRET to pharmacological therapy are lacking, and there are few randomized controlled trials that compare VRET to CBT, especially on fear of public speaking treatment.

Epidemiology of candidemia in patients with hematologic malignancies and solid tumours in Brazil.

Candidemia in cancer patients may differ according to the type of cancer. To characterise the epidemiology and outcome of candidemia in cancer patients from Brazilian hospitals, we compared the characteristics of patients with hematologic malignancies (HM) and solid tumours (ST). A retrospective study was performed, based on data collected from laboratory-based surveillance studies in 18 tertiary care hospitals between March/2003 and December/2007. The characteristics of patients with HM (n = 117) were compared with patients with ST (n = 248). Predictors of 30-day mortality were identified by uni- and multivariate analyses. Candidemia in HM was more likely to occur in the setting of chemotherapy, corticosteroids, neutropenia, mucositis and tunnelled central venous catheter (CVC), whereas surgery, intensive care unit admission and invasive procedures (mechanical ventilation, parenteral nutrition and CVC) were more frequent in ST. The 30-day mortality rate was higher in the ST group (65% vs. 46%, P = 0.001). Factors significantly associated with 30-day mortality were older age and intensive care unit admission. Important differences in the epidemiology and outcome of candidemia in HM and ST were observed. The characterisation of the epidemiology is important to drive preventive measures and to select appropriate therapies.

Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acute myeloid leukaemia or myelodysplasia in Brazil.

Invasive fungal disease (IFD) shows distinct regional incidence patterns and epidemiological features depending on the geographic region. We conducted a prospective survey in eight centres in Brazil from May 2007 to July 2009. All haematopoietic cell transplant (HCT) recipients and patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) were followed from admission until 1 year (HCT) or end of consolidation therapy (AML/MDS). The 12-month cumulative incidence (CI) of proven or probable IFD was calculated, and curves were compared using the Grey test. Among 237 AML/MDS patients and 700 HCT recipients (378 allogeneic, 322 autologous), the 1-year CI of IFD in AML/MDS, allogeneic HCT and autologous HCT was 18.7%, 11.3% and 1.9% (p <0.001), respectively. Fusariosis (23 episodes), aspergillosis (20 episodes) and candidiasis (11 episodes) were the most frequent IFD. The 1-year CI of aspergillosis and fusariosis in AML/MDS, allogeneic HCT and autologous HCT were 13.4%, 2.3% and 0% (p <0.001), and 5.2%, 3.8% and 0.6% (p 0.01), respectively. The 6-week probability of survival was 53%, and was lower in cases of fusariosis (41%). We observed a high burden of IFD and a high incidence and mortality for fusariosis in this first multicentre epidemiological study of IFD in haematological patients in Brazil.

Case report of hepatic mucormycosis after liver transplantation: successful treatment with liposomal amphotericin B followed by posaconazole sequential therapy.

Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation (SOT), with a cumulative incidence of around 2% during the first year after SOT. The associated mortality rate is high, and surgical debridement is frequently required as part of the treatment along with antifungal therapy based mostly on amphotericin B formulations, We describe here an unusual case of hepatic mucormycosis in a liver transplant recipient that was successfully treated with clinical therapy based on liposomal amphotericin B followed by posaconazole, without surgical resection.

Infection with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in solid organ transplantation.

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae is spreading globally and represents a challenge in infection control and treatment. Solid organ transplant (SOT) recipients are especially at risk for infection by multidrug-resistant bacteria, and little is known about infection with KPC-producing organisms in this setting. The aim of this study was to describe the clinical and microbiologic aspects of KPC-producing K. pneumoniae infections in SOT recipients. A KPC-2-producing K. pneumoniae outbreak was identified in a public teaching tertiary care hospital in São Paulo, Brazil, in June 2009. During the outbreak, cases of KPC-2-producing K. pneumoniae infection in SOT recipients occurred between July 2009 and February 2010; these cases were retrospectively reviewed. Overall, 12 episodes of infection with KPC-producing K. pneumoniae occurred in 2 heart, 4 liver, and 6 kidney transplant recipients with incidence rates of 16.7%, 12.9%, and 26.3% in heart, liver, and kidney transplantation, respectively. Infection occurred at a median time of 20 days after transplantation. Primary infection sites were as follows: 4 urinary tract infections, 4 bloodstream infections, 2 pneumonias, and 2 surgical site infections. All patients except one had received antibiotics in the last 30 days, mostly piperacillin-tazobactam or glycopeptides. All strains exhibited susceptibility to amikacin and gentamicin. Patients were treated with tigecycline plus polymyxin B (3 cases), polymyxin B plus carbapenem (3 cases), polymyxin B alone (3 cases), or tigecycline plus imipenem (1 case). In 2 cases, patients received only carbapenem, and death occurred before the final culture result. The overall 30-day mortality rate was 42%. In this series of KPC-producing K. pneumoniae infection in SOT recipients, the infection occurrence was high during an institutional outbreak and was potentially life threatening.

Simulation of real-time deformable soft tissues for computer assisted surgery.

The simulation of realistic surgical procedures requires specialized optimized algorithms for the models of organs and tissues, which should comply both with accuracy of results and run-time computation. This paper provides a general survey of methods and approaches used for the simulation of soft tissues in Computer Assisted Surgery, discussing the technological challenges to achieve realistic simulation of deformation.An application example is presented, referring to the simulation of a gastroenterology procedure, abdominal paracentesis for the treatment of ascites.

Assistive technology to improve PC interaction for people with intention tremor.

Many patients with upper limb intention tremor encounter difficulties in mouse-driven interaction with the personal computer (PC). An assistive technology system ("the Tremor Control System"), consisting of a motion-filtering software program that supports multiple interfaces, was developed and validated with 36 persons with Multiple Sclerosis in a multi-center trial. PC-tests, requiring basic functions such as cursor placement and click and drag function, were able to differentiate between patients and control subjects (ANOVA: p<0.05). A significant time improvement on the PC-tests was found when using an optimal alternative interface instead of the standard PC-mouse (paired t-tests: p<0.01 for Point & Click test, p<0.05 for Drag & Drop test and p<0.1 for Double Click test). A significant time improvement was found for the Double Click test (paired t-tests: p<0.05) when the motion-filtering program was implemented. The number of patients able to perform fully the PC-tests increased with the Tremor Control System. Patients with marked intention tremor seemed to profit especially from this assistive technology. These users reported that working with the Tremor Control System was less fatiguing and more comfortable compared to the use of the standard PC-mouse.

Measurement of bradykinin, protein Na+, CL-, K+, and Zn+ concentrations in rat urine after intraperitoneal injection of Tityus serrulatus venom

Experiments were carried out in vivo by injecting Tityus serrulatus crude venom in rats followed by biological assays on the isolated guinea-pig ileum, to show the effects of scorpion venom on kallikrein-kinin system. Our results showed effects such as significant decrease of total kinin rate and a decrease of total kinin rate and a decrease of Zn++, Na+, Cl- and K+ ions in rat urine 24 and 48 hours after the injection of Tityus serrulatus crude venom.

Isolation and properties of a T-kininogenase from bovine erythrocyte membranes.

A kininogenase from bovine erythrocyte membranes has been purified 140-fold by affinity chromatography on pepstatin A-Agarose followed by ion exchange chromatography on CM Cellulose. The purified enzyme showed an apparent molecular weight of 31,000 daltons as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its pH optimum is 7.5, and it was totally inhibited by soybean trypsin inhibitor, phenylmethyl-sulfonylfluoride, aprotinin, pepstatin, and dithiotreitol, suggesting the presence of a disulfide bond(s) whose integrity is(are) essential for maintaining the native three-dimensional structure. The referred enzyme was able to release kinin from a substrate partially purified from rat plasma. The kininogenase was activated by Zn2+, Ca2+, and cysteine-HCl.