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To investigate the impact of intraoperative blood transfusion on outcomes in patients who had major thoracic and lumber posterior spine instrumentation surgery. Retrospective study included patients who underwent major spine surgery between 2013 and 2017. Patients’ demographics, surgical charts, anesthesia charts, discharge charts and follow-up outpatient charts were reviewed. Data collection included: age, gender, BMI, Charlson Co-morbidity Index (CCI) scores, American Society of Anesthesiologists (ASA) scores, amount of estimated blood loss [% estimated blood volume (%EBV)], amount of blood transfused during surgery and post-surgery before discharge, number of fusion levels, pre- and postoperative hemoglobin (Hb) levels, and length of hospital stay. Also collected in-hospital postoperative complications (cardiovascular, pulmonary, infections and deaths). Patients’ postoperative intubation status data documented. Reviewed follow-up charts to document any complications. Sample size = 289; No transfusion = 92; transfusion = 197. Transfused patients were significantly older, p

Background/objective: There is a lack of information about relationship between physical characteristics and biomechanics of the lower extremity during the squat. Additionally, studies did not examine sex-related differences. The purpose of this study was to investigate relationships between physical characteristics and biomechanics of the lower extremity during the squat, and to determine if any sex differences are present. Methods: Fifty three participants recruited (21.82 ± 2.3 years; 75.56 ± 14.98 kg; 171.57 ± 8.38 cm) performed three squats with 75% of one repetition maximum. Femur to tibia length ratio, hip and ankle joints’ flexibilities, and relative muscular strength were measured and used as physical characteristics. Net joint torques (NJT) and flexion angles of the lower extremity were extracted as dependent variables. Multiple regression (stepwise) analysis was conducted to examine the relationships with physical characteristics being factors. Pearson correlation coefficients were calculated to determine intercorrelations among the dependent variables. Results: Relative muscular strength was related to hip NJT and knee flexion angle, and hip flexibility was related to ankle dorsiflexion. Hip and knee NJT showed moderate correlations with the corresponding flexion angles (r = 0.48-0.53; p

Background Pelvic fixation improves the stability of spinal instrumentation and can be used in high-grade degenerative disease, trauma, deformity, and destabilizing invasive pathologies, such as infection and tumor. Classic techniques for spinopelvic fixation include traditional iliac screws and S2-Alar-Iliac screws. We present a case series describing the distal ventral iliac pathway (DVIP) for spinopelvic fixation and discuss surgical indications and merits of this technique. We describe the use of the DVIP for spinopelvic fixation in the setting of degenerative and traumatic pathologies, compare this technique with existing approaches, and summarize literature to support this approach. Methods One hundred twenty-eight cases of DVIP screws were identified at 1 academic medical center, and 3 cases were chosen as representative examples for technique demonstration. Results Patient ages ranged from 19 to 81 (mean 62) years. Intraoperative and postoperative complications include 12 incidental durotomies, 3 suprafascial infections, and 2 compressive hematomas. There were 22 instances of hardware failure and 8 instances of pseudoarthrosis. Overall, 26 patients underwent revision surgery. Mean estimated blood loss, operative time, and time under fluoroscopy were 1959 mL, 386 minutes, and 3.19 minutes, respectively. Conclusions The DVIP is both safe and effective as a treatment for patients with degenerative and traumatic lumbosacral pathology. Spinopelvic fixation provides improved soft tissue coverage and fewer hardware complications at minimum of 1 year follow up. This case series demonstrates a novel surgical technique for spinopelvic fixation in the setting of numerous spinal pathologies. Level of Evidence 4. Clinical Relevance This surgical technique is less technically challenging than current approaches, minimizes radiation exposure, and obviates the need for horizontal connector rods. In addition, in highly destabilizing pathologies, this technique also allows for multiple screw placement within the ilium, while maintaining the ability to connect to a single rod construct. This technique is safe, technically approachable, and broadly applicable to an array of spinopelvic pathologies.

Dental implants represent the gold standard for the treatment of single edentulism, even in anterior areas. Today, the basic criteria for implant success has changed from mobility, pain, radiolucency, and peri-implant bone loss (>1.5 mm) to prosthetic level success, aesthetics, soft tissue parameters, as well as patient satisfaction. This case report documents a combination of surgical and prosthetic procedures for the treatment of gingival recessions in the anterior maxilla, appearing after tooth extraction, socket preservation, and staged guided implant placement. Prosthetic management of the temporary restoration, orthodontic treatment, and a connective tissue graft were performed. The decision-making process and step-by-step execution of the treatments are presented to describe the entire clinical and surgical management of the reported case. Finally, good aesthetic outcomes, patient satisfaction, and recovery of the soft tissue recession were observed with the combination of these techniques.

Stingless bees (Meliponini) are a monophyletic group of eusocial insects inhabiting tropical and subtropical regions. These insects represent the most abundant and diversified group of corbiculate bees. Meliponini mostly rely on fermentation by symbiont microbes to preserve honey and transform pollen in stored food. Bee nests harbor diverse microbiota that includes bacteria, yeasts, filamentous fungi, and viruses. These microorganisms may interact with the bees through symbiotic relationships, or they may act as food for the insects, or produce biomolecules that aid in the biotransformation of bee products, such as honey and bee bread. Certain microbial species can also produce antimicrobial compounds that inhibit opportunistic bee pathogens.

Patent foramen ovale (PFO) is a common congenital cardiac defect. It is usually asymptomatic, but it can be associated with relevant clinical manifestations such as cryptogenic stroke and platypnea-orthodeoxia syndrome. We present the case of a patient with hemodynamically significant carotid artery stenosis who underwent endarterectomy for a transient ischemic attack (TIA). After surgery, the patient presented an ischemic stroke due to M2 occlusion treated with mechanical thrombectomy. During hospitalization, a distal bilateral deep vein thrombosis was found. The patient developed respiratory failure due to a massive right-to-left shunt through a large PFO (platypnea-orthodeoxia syndrome). These findings are consistent with the hypothesis that the TIA and the subsequential ischemic stroke were related to paradoxical embolism rather than atherothromboembolism. The aim of our case report is to raise awareness of the possible complications of such a common finding as PFO.

Epigenetic mechanisms, such as alterations in histone acetylation based on histone deacetylases (HDACs) activity, have been linked not only to normal brain function but also to several brain disorders including epilepsy and the epileptogenic process. In WAG/Rij rats, a genetic model of absence epilepsy, epileptogenesis and mild-depression comorbidity, we investigated the effects of two HDAC inhibitors (HDACi), namely sodium butyrate (NaB), valproic acid (VPA) and their co-administration, on the development of absence seizures and related psychiatric/neurologic comorbidities following two different experimental paradigms. Treatment effects have been evaluated by EEG recordings (EEG) and behavioural tests at different time points. Prolonged and daily VPA and NaB treatment, started before absence seizure onset (P30), significantly reduced the development of absence epilepsy showing antiepileptogenic effects. These effects were enhanced by NaB/VPA co-administration. Furthermore, early-chronic HDACi treatment improved depressive-like behaviour and cognitive performance 1 month after treatment withdrawal. WAG/Rij rats of 7 months of age showed reduced acetylated levels of histone H3 and H4, analysed by Western Blotting of homogenized brain, in comparison to WAG/Rij before seizure onset (P30). The brain histone acetylation increased significantly during treatment with NaB or VPA alone and more markedly during co-administration. We also observed decreased expression of both HDAC1 and 3 following HDACi treatment compared to control group. Our results suggest that histone modifications may have a crucial role in the development of epilepsy and early treatment with HDACi might be a possible strategy for preventing epileptogenesis also affecting behavioural comorbidities.

Introduction Epilepsy represents the third most common neurological disorder in the elderly. Antiseizure medications (ASMs) are often used not only to treat epilepsy but also other disorders in this age group. Many physio-pathological changes occur in body composition and organ or system functions with aging. Furthermore, drug-drug interactions (DDIs) represent a major risk considering the prevalence of polytherapy in the elderly. Areas covered Relevant studies on the pharmacokinetics of ASMs in the elderly were identified through a literature search. We have reviewed all available data on known alterations in pharmacokinetic parameters of ASMs in elderly also considering pathophysiological alterations such as renal function impairment. Finally, we have highlighted the potential risk of DDIs with some drug classes. Expert opinion Large interindividual variability also due to co-morbidities and related co-therapies makes elderly patients a not homogeneous group. Overall, a reduction in loading and maintenance doses of almost all ASMs should be considered to avoid adverse events (AEs) as well as a slow titration, following the rule 'start low and go slow'. Therapeutic drug monitoring should be performed to apply the 'individual therapeutic concentration' and implemented to overcome the age-related differences between dose and plasma concentrations, to monitor DDIs and guide dosage adjustments.

Increased expression of interleukin-6 (IL-6) both in cerebrospinal fluid (CSF) and plasma is closely associated with convulsive epilepsy and symptom severity of depression. By comparison, at present, little is known about the role of this cytokine in childhood (non-convulsive) absence epilepsy. The aim of this work was to investigate the potential effects of acute and chronic treatment with tocilizumab (TCZ, 10 and 30 mg/kg/day), on absence seizures, their development, and related psychiatric comorbidity in WAG/Rij rats. It is known that lipopolysaccharide (LPS)-induced changes in inflammatory processes increase absence epileptic activity. In order to study the central effects of TCZ, we investigated whether administration of this anti-IL-6R antibody could modulate the lipopolysaccharide (LPS) or IL-6-evoked changes in absence epileptic activity in WAG/Rij rats. Our results demonstrate that TCZ, at both doses, significantly reduced the development of absence seizures in adult WAG/Rij rats at 6 months of age (1 month after treatment suspension) compared with untreated controls, thus showing disease-modifying effects. Decreased absence seizure development at 6 months of age was also accompanied by reduced comorbid depressive-like behavior, whereas no effects were observed on anxiety-related behavior. Acute treatment with TCZ, at 30 mg/kg, had anti-absence properties lasting ~25 h. The co-administration TCZ with i.c.v. LPS or IL-6 showed that TCZ inhibited the worsening of absence seizures induced by both proinflammatory agents in the WAG/Rij rats, supporting a central anti-inflammatory-like protective action. These results suggest the possible role of IL-6 and consequent neuroinflammation in the epileptogenic process underlying the development and maintenance of absence seizures in WAG/Rij rats. Accordingly, IL-6 signaling could be a promising pharmacological target in absence epilepsy and depressive-like comorbidity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00893-8) contains supplementary material, which is available to authorized users.

Background Splenic artery aneurysm (SAA) and pseudoaneurysm are rare vessel's lesions. Pseudoaneurysm is often symptomatic and secondary to pancreatitis or trauma. True SAA is the most common aneurysm of visceral vessels. In contrast to pseudoaneurysm, SAA is usually asymptomatic until the rupture, with high mortality rate. The clinical onset of SSA's rupture is a massive life-threatening bleeding with hemodynamic instability, usually into the free peritoneal space and more rarely into the gastrointestinal tract. Case summary We describe the case of a 35-year-old male patient, with negative past medical history, who presented to the emergency department for massive upper gastrointestinal bleeding, severe anemia and hypotension. An esophagogastroduodenoscopy performed in emergency showed a gastric bulging in the greater curvature/posterior wall with a small erosion on its surface, with a visible vessel, but no active bleeding. Endoscopic injection therapy with cyanoacrylate glue was performed. Urgent contrast-enhanced computed tomography was carried out due to the clinical scenario and the unclear endoscopic aspect: The radiological examination showed a giant SAA which was adherent to posterior stomach wall, and some smaller aneurysms of the left gastric and ileocolic artery. Because of the high risk of a two-stage rupture of the giant SAA with dramatic outcome, the patient underwent immediate open surgery with aneurysmectomy, splenectomy and distal pancreatectomy with a good postoperative outcome. Conclusion The management of a ruptured giant SAA into the stomach can be successful with surgical approach.

Rehabilitation of atrophic maxilla still remains a challenge. Fixed implant-supported restorations have become more predictable in the last years, nevertheless, technical and biological complications still occur. Removable overdenture fully supported by a CAD/CAM titanium bar seems to be a viable treatment option for the rehabilitation of completely edentulous patients with a high degree of bone resorption. In these clinical cases, the soft tissues of the lower third of the face need to be respected, and a fixed-removable solution is the only option to have good hygiene control. Nevertheless, there is no consensus about the optimal number and position of the implants. A total of six adult patients were recruited and treated with an overdenture fully supported by a CAD/CAM titanium bar and low-profile attachment, screwed on four or six implants. A detailed step-by-step description of the procedures was presented. Overall, all the patients were successful treated with no relevant complications. With the limitations of this case series, maxillary implant overdenture fully supported by four or six implants seems to be a safer treatment option for the minimally invasive rehabilitation of atrophic maxillae, regardless of the number of implants.

Social insects establish complex interactions with microorganisms, some of which play defensive roles in colony protection. The important role of pollinators such as the stingless bee Melipona scutellaris in nature encouraged us to pursue efforts to study its associated microbiota. Here we describe the discovery of two novel cyclic hexadepsipeptides, meliponamycin A (1) and meliponamycin B (2), from Streptomyces sp. ICBG1318 isolated from M. scutellaris nurse bees. Their structures were established by interpretation of NMR and MS data, and the absolute configuration of the constituent amino acids was determined by the advanced Marfey's method. Compounds 1 and 2 showed strong activity against the entomopathogen Paenibacillus larvae and human pathogens Staphylococcus aureus and Leishmania infantum.

Typically, healing or temporary abutments are connected and disconnected several times between implant placement and definitive restoration delivery, and soft tissue disruption occurs each time the abutment is disconnected and reconnected. This histologic event is supposed to cause bone resorption around the implant after second-stage surgery. To minimize this clinical scenario, immediately placing and never removing a definitive abutment the day of implant insertion (one-stage protocol) or at second-stage surgery in cases of submerged implants (two-stage protocol) was suggested. This paper details the prosthetic protocol and presents strategies and rationales for placing a definitive abutment the day of implant insertion or at second-stage surgery with cement- and screw-retained restorations. This protocol seems to be an efficient strategy to preserve peri-implant hard and soft tissues. However, positive outcomes in peri-implant bone and soft level changes should be viewed with caution, as their clinical significance is still uncertain.

Made available in DSpace on 2022-04-29T08:32:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Imbalances in gut microbiota composition occur in individuals with autism spectrum disorder (ASD). The administration of probiotics, prebiotics, and synbiotics is emerging as a potential and promising strategy for regulating the gut microbiota and improving ASD-related symptoms. We first investigated the survival of the probiotics Limosilactobacillus (L.) reuteri and Bifidobacterium (B.) longum alone, mixed and combined with a galacto-oligosaccharide (GOS) under simulated gastrointestinal conditions. Next, we evaluated the impact of probiotics (L. reuteri + B. longum), prebiotic (GOS), and synbiotic (L. reuteri + B. longum + GOS) on gut microbiota composition and metabolism of children with ASD using an in vitro fermentation model (SHIME®). The combination of L. reuteri, B. longum, and GOS showed elevated gastrointestinal resistance. The probiotic, prebiotic, and synbiotic treatments resulted in a positive modulation of the gut microbiota and metabolic activity of children with ASD. More specifically, the probiotic treatment increased the relative abundance of Lactobacillus, while the prebiotic treatment increased the relative abundance of Bifidobacterium and decreased the relative abundance of Lachnoclostridium. Changes in microbial metabolism were associated with increased short-chain fatty acid concentrations and reduced ammonium levels, particularly in the prebiotic and synbiotic treatments. Department of Food and Nutrition School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Hydraulics and Sanitation School of Engineering of São Carlos University of São Paulo (USP) Department of Internal Medicine UC Davis School of Medicine University of California INRAE UNH Université Clermont Auvergne Faculty of Pharmacy Paris University Food and Human Nutrition Research Group University of Antioquia Department of Food and Nutrition School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP) FAPESP: 2017/01157-1 FAPESP: 2018/26645-1

Objective A large number of studies have highlighted the important role of the gut microbiota in the pathophysiology of neurological disorders, suggesting that its manipulation might serve as a treatment strategy. We hypothesized that the gut microbiota participates in absence seizure development and maintenance in the WAG/Rij rat model and tested this hypothesis by evaluating potential gut microbiota and intestinal alterations in the model, as well as measuring the impact of microbiota manipulation using fecal microbiota transplantation (FMT). Methods Initially, gut microbiota composition and intestinal histology of WAG/Rij rats (a well-recognized genetic model of absence epilepsy) were studied at 1, 4, and 8 months of age in comparison to nonepileptic Wistar rats. Subsequently, in a second set of experiments, at 6 months of age, untreated Wistar or WAG/Rij rats treated with ethosuximide (ETH) were used as gut microbiota donors for FMT in WAG/Rij rats, and electroencephalographic (EEG) recordings were obtained over 4 weeks. At the end of FMT, stool and gut samples were collected, absence seizures were measured on EEG recordings, and microbiota analysis and histopathological examinations were performed. Results Gut microbiota analysis showed differences in beta diversity and specific phylotypes at all ages considered and significant variances in the Bacteroidetes/Firmicutes ratio between Wistar and WAG/Rij rats. FMT, from both Wistar and ETH-treated WAG/Rij donors to WAG/Rij rats, significantly decreased the number and duration of seizures. Histological results indicated that WAG/Rij rats were characterized by intestinal villi disruption and inflammatory infiltrates already at 1 month of age, before seizure occurrence; FMT partially restored intestinal morphology while also significantly modifying gut microbiota and concomitantly reducing absence seizures. Significance Our results demonstrate for the first time that the gut microbiota is modified and contributes to seizure occurrence in a genetic animal model of absence epilepsy and that its manipulation may be a suitable therapeutic target for absence seizure management.

Sodiumvalproate (VPA), an antiepileptic drug, may cause dose- and time-dependent hepatotoxicity. However, its iatrogenic molecular mechanism and the rescue therapy are disregarded. Recently, it has been demonstrated that sodium butyrate (NaB) reduces hepatic steatosis, improving respiratory capacity and mitochondrial dysfunction in obese mice. Here, we investigated the protective effect of NaB in counteracting VPA-induced hepatotoxicity using in vitro and in vivo models. Human HepG2 cells and primary rat hepatocytes were exposed to high VPA concentration and treated with NaB. Mitochondrial function, lipid metabolism, and oxidative stress were evaluated, using Seahorse analyzer, spectrophotometric, and biochemical determinations. Liver protection by NaB was also evaluated in VPA-treated epileptic WAG/Rij rats, receiving NaB for 6months. NaB prevented VPA toxicity, limiting cell oxidative and mitochondrial damage (ROS, malondialdehyde, SOD activity, mitochondrial bioenergetics), and restoring fatty acid oxidation (peroxisome proliferator-activated receptor α expression and carnitine palmitoyl-transferase activity) in HepG2 cells, primary hepatocytes, and isolated mitochondria. In vivo, NaB confirmed its activity normalizing hepatic biomarkers, fatty acid metabolism, and reducing inflammation and fibrosis induced by VPA. These data support the protective potential of NaB on VPA-induced liver injury, indicating it as valid therapeutic approach in counteracting this common side effect due to VPA chronic treatment.

We calculate the change in effusion rate of lava from a volcanic fissure due to pressure changes in the volcanic conduit. The conduit is modelled as a cylinder with elliptical cross-section, embedded in an elastic medium. The elliptical shape can represent a wide range of cross-sections, according to the value of eccentricity, from almost circular vents to very long and narrow fissures. A 2-D problem is considered assuming invariance of pressure changes and conduit geometry with depth. The problem is solved analytically and expressions for the displacement and the stress fields in the elastic medium are provided. The displacement of the conduit wall is proportional to the ratio between the pressure change and the rigidity of surrounding rocks. The flow rate is a nonlinear function of the pressure change and increases with increasing pressure, due to the elastic deformation of the conduit wall.We consider flow rate oscillations with periods ranging from several minutes to hours, as are often observed during effusive eruptions. Assuming pressure oscillations with these periods, flow rate oscillations resulting from the elastic deformation of the conduit are calculated. The greatest oscillations in flow rate are obtained for very large values of the conduit eccentricity, corresponding to long and narrow volcanic fissures. For example, if a fissure is 100 m long and 2 m large, a pressure oscillation with an amplitude of 1 MPa yields a maximum displacement of the conduit wall equal to about 6 cm and an amplitude of flow rate oscillations of about 20 per cent.

The Microbiota-Gut-Brain axis (MGBA) is a bidirectional communication pathway between gut bacteria and the central nervous system (CNS) (including the intestine) that exerts a profound influence on neural development, neuroinflammation, activation of stress response and neurotransmission, in addition to modulating complex behaviours, such as sociability and anxiety. Several MGBA modulating approaches are possible, such as probiotic administration. A reasonable pharmacological approach would also be the contemporarily administration of both prebiotics and postbiotics. To test this hypothesis, we probed the effects of α-lactalbumin (ALAC; a prebiotic in the dose range of 125–500 mg/kg) and sodium butyrate (NaB; a postbiotic in the dose range of 30–300 mg/kg) alone and in combination. We used two animal behavioural models of idiopathic autism, (BTBR mice) and anxiety/depression (chronic unexpected mild stress - CUMS mice) respectively, using several standard behavioural paradigms such as Three-chamber social interaction test, Marble burying assay, depression-, anxiety- and memory-tests. In BTBR autistic mice, we found that both ALAC and NaB improve animal sociability, and memory in the passive avoidance (PA); drug combination was more effective in almost all tests also reducing immobility time in the forced swimming test (FST), which was not affected by single drug administration. Similarly, in the CUMS mice, single drug administration was effective in improving: 1) depressive-like behaviour in the FST and sucrose preference test; 2) memory and learning in the PA, novel object recognition and Morris water maze tests. Drug combination was again more effective than single drug administration in most cases; however, in the CUMS model, neither single drug or combination was effective in the elevated plus maze test for anxiety. Our results suggest that in both models, ALAC and NaB combination is more effective in improving some pathological aspects of animal behaviour than single administration and that the prebiotic/postbiotic approach should be considered a reasonable approach for the manipulation of the MGBA to improve efficacy.

To examine whether free (3-PD-5free) and/or liposomal (3-PD-5lipo) 6,7-dihydroxy-3-[3′,4′-methylenedioxyphenyl]-coumarin (3-PD-5) (1) modulate the effector functions of neutrophils from patients with rheumatoid arthritis under remission (i-RA) and with active disease (a-RA), in vitro; and (2) exert anti-inflammatory effect in a rat model of zymosan-induced acute joint inflammation. Incorporation of 3-PD-5 into unilamellar liposomes of soya phosphatidylcholine and cholesterol was efficient (57.5 ± 7.9%) and yielded vesicles with low diameter (133.7 ± 18.4 nm), polydispersity index (0.39 ± 0.06), and zeta potential (− 1.22 ± 0.34 mV). 3-PD-5free (1 µM) and 3-PD-5lipo (3 µM) equally suppressed elastase release and reactive oxygen species generation in neutrophils from healthy subjects and i-RA and a-RA patients, stimulated with immune complexes. 3-PD-5free (20 µM) suppressed the release of neutrophil extracellular traps and chemotaxis in vitro, without clear signs of cytotoxicity. 3-PD-5lipo (1.5 mg/kg, i.p.) diminished joint edema and synovial infiltration of total leukocytes and neutrophils, without changing the synovial levels of TNF-α, IL-1β, and IL-6. Altogether, the results reported herein indicate that 3-PD-5 is a promising modulator of the early stages of acute joint inflammation that can help to diminish not only excessive neutrophil infiltration in the synovia but also neutrophil activation and its outcomes in RA patients.

Liraglutide (LIR) is a novel long-lasting glucagon-like peptide-1 (GLP-1) analogue that facilitates insulin signalling and shows also neuroprotective properties in different brain disease models. In this study, we explored the potential antiepileptogenic effects of LIR in two different animal models; namely, the mouse intrahippocampal kainic acid (KA) model of temporal lobe epilepsy and the WAG/Rij rat model of absence epileptogenesis. Moreover, we evaluated LIR effects on comorbidities in various behavioural tests. Mice with kainate-induced epilepsy were treated with LIR (300 μg/kg/day s.c.) for 4 weeks after status epilepticus and then evaluated for drug effects on seizure development and behavioural alterations, whereas WAG/Rij rats were treated for 17 weeks (starting at 30 days of age, before seizure onset) with LIR (300 μg/kg/day s.c.) in order to investigate whether an early chronic treatment was able to reduce the development of absence seizures and related comorbidities. Our results indicate that LIR was effective in reducing the development of spontaneous seizures in kainate-induced epilepsy; moreover, in this model, it prevented memory impairment and related anxiety-like behaviour in the open field (OF) test while in the forced swimming test (FST), LIR displayed an apparent pro-depressant effect that was instead related to reduced endurance as confirmed by Rotarod test. In contrast, LIR was unable to modify the epileptogenic process underlying the development of absence seizures in WAG/Rij rats while being antidepressant in the FST in this strain. Our results indicate that LIR may represent a promising novel treatment to prevent and treat the epileptogenic process and its associated behavioural and cognitive alterations in some models of convulsive epilepsy characterized by neurodegeneration, since LIR effects are likely secondary to its recognized neuroprotective properties.

Objective Provide recommendations to the cystic fibrosis (CF) community to facilitate timely referral for lung transplantation for individuals with CF. Methods The CF Foundation organized a multidisciplinary committee to develop CF Lung Transplant Referral Consensus Guidelines. Three workgroups were formed: timing for transplant referral; modifiable barriers to transplant; and transition to transplant care. A focus group of lung transplant recipients with CF and spouses of CF recipients informed guideline development. Results The committee formulated 21 recommendation statements based on literature review, committee member practices, focus group insights, and in response to public comment. Critical approaches to optimizing access to lung transplant include early discussion of this treatment option, assessment for modifiable barriers to transplant, and open communication between the CF and lung transplant centers. Conclusions These guidelines will help CF providers counsel their patients and may reduce the number of individuals with CF who die without consideration for lung transplant.

Objective Prevertebral soft tissue swelling (PSTS) is a known complication of anterior cervical fusion (ACF). Prior studies have shown that perioperative steroids may reduce PSTS after ACF. We retrospectively evaluated the role of perioperative intravenous (IV) corticosteroid administration in minimizing radiographic PSTS measurements in patients undergoing ACF for degenerative disease. Methods Records of 100 consecutive patients undergoing ACF for degenerative disease (Current Procedural Terminology code 63075) from January 2010 through December 2012 by 2 orthopedic spine fellowship-trained surgeons at a single institution were retrospectively reviewed. Patients were included on the basis of specific criteria. They were then separated into comparison and IV steroid groups. Demographic and surgical data were collected. Last, measurements of PSTS, which included PSTS ratio and PSTS index (PSTSI), were obtained from plain radiographs preoperatively and at 3 postoperative time points. Results Eighty patients were included; 26 received IV steroids at the surgeon's discretion (12 intraoperatively, 11 postoperatively and 3 at both time periods). With the exception of a history of prior anterior cervical spine surgery (3.70% comparison vs. 23.08% IV steroid, P = 0.01), there was no statistically significant demographic characteristic. Furthermore, there was no statistically significant surgical characteristic. Last, there was no statistically significant difference between groups at any time point for either PSTS ratio at any level or PSTSI. Conclusions There does not appear to be a role for perioperative IV steroid administration in minimizing radiographic PSTS in patients undergoing ACF for degenerative disease. The relationship between perioperative IV steroid administration and PSTS requires further investigation.

The discovery of potential antiseizure drugs (ASDs) requires the use of experimental models that can also provide a unique chance for identifying new effective molecules able to prevent and/or cure epilepsy. Most of the preclinical knowledge on epileptogenesis derives from studies performed on post-insult models that are characterized by a recognizable first insult, a silent period lasting until the onset of the first seizure and a chronic period characterized by spontaneous recurrent seizures (SRSs). At odds, genetic models, in which the first insult remains to be identified, have been poorly investigated. Among the genetic models, the WAG/Rij rat was validated as a suitable experimental model of absence epileptogenesis with neuropsychiatric symptomatology, in which, according to our previous hypothesis on SRSs onset, genes could be considered the first ‘insult’ underlying all plastic modifications supporting the occurrences of absence seizures in this strain. In fact, in several genetic models, the initial insult could be described as the mutation leading to epilepsy that, to date, remains to be defined in this strain. The silent period ends at the occurrence of the first SRS, which is approximately at 2-3 months of age in these rats and after that time the chronic phase initiates, in which, absence seizures increase over time underlying likely further epileptogenic processes. In this review, we describe both the features of this experimental model and the effects of several pharmacological treatments against epileptogenesis and its related comorbidities including depressive-like symptoms and cognitive decline.

Objective The objective of this study is to compare the implant stability of Hiossen ET III implants with its new hydrophilic (NH) surface and Hiossen ET III implants with the sandblasted and acid-etched (SA) surface. Materials and Methods Patients required at least two teeth to be rehabilitated with a fixed, implant-supported restoration, consecutively enrolled. Patients randomly received SA surface implants (SA group) or SA implants with a newly developed bioabsorbable apatite nanocoating (NH group). Outcome measures were implant and prosthetic survival rate, complications, insertion torque, and implant stability quotient (ISQ) measured at implant placement and every week up to 8 weeks after implant placement. Comparison between groups was made by unpaired t-test, while the comparison between each follow-up will be made by paired t-tests to detect any change during the follow-up. Complications and failures were compared using Fisher's exact test. Results A total of 14 patients were treated with 28 implants (14 SA and 14 NH). No implant and prosthesis failed 4 months after implant placement. No complications were experienced. At the 2nd week after implants placement, two implants in the SA group showed discontinuous measurements versus none in the NH group (p = 0.4815). Implants unscrewed during ISQ measurements and were rescrewed. Data recording stopped for 6 weeks. Both implants osseointegrated without any further complication. The NH implants did not show physiological ISQ decrease between 2nd and 4th week after implant placement, showing a more even pattern of ISQ values compared with SA implants (77.1 ± 4.6 vs. 72.9 ± 11.5; difference: 4.2 ± 12.1; p = 0.258). High ISQ values were found in both groups at each time point. Conclusions NH implants are a viable alternative to SA surface, as they seem to avoid the ISQ drop during the remodeling phase.

The purpose of this case report was to present a combination of two procedures in the treatment of gingival recessions after implant placement in the anterior maxilla. Decision making process and step-by-step execution of the treatments were presented to describe the clinical and surgical management of the reported case.

Background The purpose of this study was to evaluate outcomes in people with cystic fibrosis (CF) who underwent lung transplant (LT) at a transplant center with an accredited Cystic Fibrosis Care Center (CFCC) in the United States. Methods We reviewed the Scientific Registry of Transplant Recipients for all adult patients with CF who received a first-time LT from 2005 to 2018. The primary outcome was graft failure. Unadjusted Kaplan-Meier analysis and adjusted multilevel Cox proportional hazards models were used to evaluate outcomes in CF patients undergoing lung transplantation at a CFCC. Results 2,573 patients with CF underwent a first time LT during the study period. Of the 68 lung transplantation centers, 50 were CFCCs (73.5%). After adjustment for potential confounders, patients who underwent lung transplantation at a hospital with an accredited CFCC had a 33% reduction in risk of death or re-transplantation compared to those transplanted at a hospital without an accredited CFCC (HR: 0.67, 95% CI: 0.56-0.82, p Conclusion People with CF who undergo LT at a transplant center with a CFCC have improved graft survival and decreased need for re-transplantation compared to those who undergo LT at a non-CFCC, independent of volume.

The long pentraxin PTX3 is generating great interest given the recent discovery of its involvement in bone metabolism. This study investigates the role of circulating PTX3 as a marker of bone-related phenotypes in patients with osteoporosis (OP) and osteoarthritis (OA).Serum PTX3 levels were determined using an enzyme-linked immunosorbent assay (ELISA) in a total of OP (n=32), OA (n=19) patients and healthy controls (CTR; n=25). ROC curve analysis was carried out to evaluate the potential of PTX3 for the diagnosis of bone-related phenotypes. In addition, the association between PTX3 serum levels and biochemical markers was estimated by Spearman correlation analysis.Serum analysis reveals a statistically significant increase of PTX3 levels in OP and OA patients, compared to CTR subjects (**** p 0.0001, **** p 0.0001). ROC curve of PTX3 levels exhibits an excellent sensitivity and specificity for OP and OA diseases (**** p 0.0001 and **** p 0.0001, respectively). Moreover, serum PTX3 levels are positively associated with ALP (r = - 0.5257, p = 0.0083) and PTH levels (r = 0.4704, p = 0.0203) in OP patients.These results confirm the pivotal role of PTX3 in bone metabolism and suggest its potential use as a predictor of OP and OA bone-related phenotypes.

Background The long pentraxin PTX3 is generating great interest given the recent discovery of its involvement in bone metabolism. This study investigates the role of circulating PTX3 as a marker of bone-related phenotypes in patients with osteoporosis (OP) and osteoarthritis (OA). Methods Serum PTX3 levels were determined using an enzyme-linked immunosorbent assay (ELISA) in a total of OP (n=32), OA (n=19) patients and healthy controls (CTR; n=25). ROC curve analysis was carried out to evaluate the potential of PTX3 for the diagnosis of bone-related phenotypes. In addition, the association between PTX3 serum levels and biochemical markers was estimated by Spearman correlation analysis. Results Serum analysis reveals a statistically significant increase of PTX3 levels in OP and OA patients, compared to CTR subjects (**** p p p p r = − 0.5257, p = 0.0083) and PTH levels (r = 0.4704, p = 0.0203) in OP patients. Conclusions These results confirm the pivotal role of PTX3 in bone metabolism and suggest its potential use as a predictor of OP and OA bone-related phenotypes.

Schistosomiasis is a parasitic disease that affects more than 250 million people. The treatment is limited to praziquantel and the control of the intermediate host with the highly toxic molluscicidal niclosamide. Marine algae are a poorly explored and promising alternative that can provide lead compounds, and the use of multivariate analysis could contribute to quicker discovery. As part of our search for new natural compounds with which to control schistosomiasis, we screened 45 crude extracts obtained from 37 Brazilian seaweed species for their molluscicidal activity against Biomphalaria glabrata embryos and schistosomicidal activities against Schistosoma mansoni. Two sets of extracts were taxonomically grouped for metabolomic analysis. The extracts were analyzed by GC–MS, and the data were subjected to Pattern Hunter and Pearson correlation tests. Overall, 22 species (60%) showed activity in at least one of the two models. Multivariate analysis pointed towards 3 hits against B. glabrata veliger embryos in the Laurencia/Laurenciella set, 5 hits against B. glabrata blastula embryos, and 31 against S. mansoni in the Ochrophyta set. Preliminary annotations suggested some compounds such as triquinane alcohols, prenylated guaianes, dichotomanes, and xenianes. Despite the putative identification, this work presents potential candidates and can guide future isolation and identification.

Invertebrate model organisms (the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster) are valuable tools to bridge the gap between traditional in vitro discovery and preclinical animal models. Invertebrate model organisms are poised to serve as better disease models than 2D cellular monocultures for drug discovery, as well as easier and more cost-effective to scale up than 3D organoids/assembloids or co-cultures. A strength of model organisms is the opportunity to probe conserved biology such as lysosomal function and autophagy in a physiological setting. However, invertebrate models are not without pharmacokinetic and pharmacodynamic challenges, such as poor tissue penetration and confidence in a compound’s mechanism of action. To confront those challenges, we took advantage of the Novartis mechanism-of-action box (MoA Box), a compound library of well-annotated and drug-like chemical probes. Curious as to how the MoA Box, comprised of chemical probes optimized for mammalian targets, would fare in an invertebrate setting we screened the MoA Box across three different models of the lysosomal storage disease mucolipidosis Type IV (MLIV). MLIV is caused by mutations in the lysosomal transient receptor potential ion channel mucolipin-1 (TRPML1) resulting in hyper-acidic lysosomes and dysregulated autophagy. The overlap of screening hits from worm, fly, and patient fibroblast screens identified cyclin-dependent kinase (CDK) inhibition as an evolutionarily conserved disease modifier and potential drug repurposing strategy.Summary statementA trio of phenotypic screens across Drosophila, C. elegans, and H. sapiens models of mucolipidosis IV was performed and identified overlapping hits including cyclin-dependent kinase inhibitors.

Three antifungal macrolides cyphomycin (1), caniferolide C (2) and GT-35 (3) were isolated from Streptomyces sp. ISID311, a bacterial symbiont associated with Cyphomyrmex fungus-growing ants. The planar structures of these compounds were established by 1 and 2D NMR data and MS analysis. The relative configurations of 1–3 were established using Kishi's universal NMR database method, NOE/ROE analysis and coupling constants analysis assisted by comparisons with NMR data of related compounds. Detailed bioinformatic analysis of cyphomycin biosynthetic gene cluster confirmed the stereochemical assignments. Compounds 1–3 displayed high antagonism against different strains of Escovopsis sp., pathogen fungi specialized to the fungus-growing ant system. Compounds 1–3 also exhibited potent antiprotozoal activity against intracellular amastigotes of the human parasite Leishmania donovani with IC50 values of 2.32, 0.091 and 0.073 µM, respectively, with high selectivity indexes.

The purpose of this multicenter randomized controlled trial was to compare the clinical, radiographic, and patient-centered outcomes of early loaded mandibular overdentures deliberately placed on two or three implants. The outcomes were: implant and prosthesis success and survival rates; biological and technical complications; marginal bone loss; patient satisfaction; and periodontal parameters. The results showed no differences between the groups in any of the outcomes analyzed. With the limitations of the present study, and looking at long-term follow-up, the gold standard of prosthetic rehabilitations with attachments, in agreement with the scientific community, should prefer two non-splinted implants.

A dental implant is a medical device used to functionally and aesthetically rehabilitate the lack of one or more teeth, allowing the support of a prosthetic substitute through direct bone support [...]

Abstract Objective Preliminary data on survival and success rates of immediately loaded, maxillary, screw-retained, implant-supported, fixed restorations delivered on narrow and low-profile OT Equator abutments (OT Bridge, Rhein’83) were evaluated. Materials and Methods This retrospective study evaluated data collected from patients rehabilitated with OT Bridge prosthetic concept between November 2017 and February 2019 in six different centers. Outcome measures were implant and prosthetic survival rates, biological and technical complications, marginal bone loss (MBL), oral health impact profile (OHIP), bleeding on probing, and plaque index. Results A total of 76 implants were inserted in 14 patients. Patients were followed for a mean period of 15.8 months (range = 12–24). All the patients receive OT Equator (Rhein'83) as intermediate abutments. One year after loading, one implant failed (1.3%). None of the prosthesis failed. One prosthetic complication was experienced in one patient. Three out of 76 implants were connected to the prosthetic framework using only the Seeger system, without screw. Difference in OHIP values was statistically significant (71.9 ± 8.5; p = 0.000). One year after loading, MBL was 0.21 ± 0.11 mm and p-value was 0.000. One year after loading, 8.7% of the examined implant sites present positive bleeding on probing, while 6.4% of the implant sites presented plaque. Conclusion The OT Equator abutments (Rhein'83) showed successful results when used to support maxillary fixed dental prosthesis delivered on four to six implants. High implant and prosthetic survival rates, very low complications, high patient satisfaction, and good biological parameters, including only 0.2 mm of bone remodeling were experienced one year after function. Further studies are needed to confirm these preliminary results.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of metabolic syndrome, a risk factor for mortality and cardiovascular morbidity, but we ignore the role of steatosis per se in survival, and there is very little information about this condition in the geriatric patient. AIMS: With the present study, we investigated the independent prognostic value of NAFLD on overall mortality in the elderly. METHODS: Within the Pianoro Project, involving people ≥ 65 years, anamnestic, clinical and laboratoristic data related to NAFLD, insulin resistance, diabetes/hyperglycemia, hypertension, obesity and dyslipidemia were collected in 804 subjects (403 male, 401 female). These subjects were followed up for mortality for a median time of 12.6 years. A multivariate analysis was performed to evaluate the prognostic value of the covariates. RESULTS: At Kaplan-Meier estimator the presence of NAFLD seems to be associated to a lower mortality, and survival tends to increase with the increasing of steatosis grade. Cox's analysis found that survival is increased for subjects having hypercholesterolemia (RR = 0.565), NAFLD (RR = 0.777), hypertension (RR = 0.711) and in female (RR = 0.741), while it is decreased for the older subjects (RR = 3.046), in patients with hypertriglyceridemia (RR = 1.699) and for diabetics (RR = 1.797). The variables BMI and HDL-cholesterol have no role. CONCLUSION: The data obtained in our study show that NAFLD is not associated to overall mortality in the elderly population.

The Brazilian stingless bee Scaptotrigona depilis requires the brood cells-associated fungus Zygosaccharomyces sp. as steroid source for metamorphosis. Besides the presence of Zygosaccharomyces sp., other fungi inhabit S. depilis brood cells, but their biological functions are unknown. Here we show that Candida sp. and Monascus ruber, isolated from cerumen of S. depilis brood provisions, interact with Zygosaccharomyces sp. and modulate its growth. Candida sp. produces volatile organic compounds (VOCs) that stimulate Zygosacchromyces sp. development. Monascus ruber inhibits Zygosacchromyces sp. growth by producing lovastatin, which blocks steroid biosynthesis. We also observed that in co-cultures M. ruber inhibits Candida sp. through the production of monascin. The modulation of Zygosaccharomyces sp. growth by brood cell-associated fungi suggests their involvement in S. depilis larval development. This tripartite fungal community opens new perspectives in the research of microbial interactions with bees. Made available in DSpace on 2019-11-26T18:13:46Z (GMT). No. of bitstreams: 1 MenezesMicrobialCommunities2019.pdf: 1605731 bytes, checksum: eac5cfd1729fbd12538d1a0a22b5e1cf (MD5) Previous issue date: 2019

BACKGROUND Surgical templates are classified as noncritical devices, and they do not need to be sterile. AIM Primary aim of this study was to assess the microbiological burden present on the surgical templates without metallic sleeves after disinfection. Furthermore, to evaluate trueness after disinfection and steam sterilization at 121°C/15 min, and over a 8-week storage period. Finally, to assess their accuracy after in vitro implant placement simulation. MATERIALS AND METHODS Forty surgical templates were printed and divided in five groups of eight templates each. Groups A to C were disinfected with 0.5% Chlorhexidine Gluconate and 70% ethyl alcohol base solution for 15 min. Templates in the group D were steam sterilized at 121°C for 15 min, while, the templates in the group E were used as control. Implant simulation was performed in the group A. Outcome measures were determination of bioburden, trueness assessment using GOM Inspect Professional software, and accuracy evaluated thought the mean angular deviation of simulated implants. RESULTS Total microbic charge measured as colony forming units (CFU) for sample, was 24.40 in the control group (group E; n = 8), and