ALS-associated VRK1 R321C mutation causes proteostatic imbalance and mitochondrial defects in iPSC-derived motor neurons.

Vaccinia-related kinase 1 (VRK1) is a gene which has been implicated in the pathological process of a broad range of neurodevelopmental disorders as well as neuropathies, such as Amyotrophic Lateral Sclerosis (ALS). Here we report a family presenting ALS in an autosomal recessive mode of inheritance, segregating with a homozygous missense mutation located in VRK1 gene (p.R321C; Arg321Cys). Proteomic analyses from iPSC-derived motor neurons identified 720 proteins eligible for subsequent investigation, and our exploration of protein profiles revealed significant enrichments in pathways such as mTOR signaling, E2F, MYC targets, DNA repair response, cell proliferation and energetic metabolism. Functional studies further validated such alterations, showing that affected motor neurons presented decreased levels of global protein output, ER stress and downregulation of mTOR signaling. Mitochondrial alterations also pointed to decreased reserve capacity and increased non-mitochondrial oxygen consumption. Taken together, our results present the main pathological alterations associated with VRK1 mutation in ALS.

Neuroendocrine response to diclofenac in healthy subjects: a pilot study.

PURPOSE: The precise effects of non-steroidal anti-inflammatory drugs on the neuroendocrine hydro-electrolytic regulation are not precisely understood. The aim of this pilot study was to evaluate, in healthy subjects, the neuroendocrine response of the antidiuretic system to intravenous diclofenac infusion. METHODS: For this single-blinded, cross-over study, we recruited 12 healthy subjects (50% women). Test sessions were divided into three observation times (pre-test; test; 48 h post-test), which were repeated equally on two different occasions, with the administration of diclofenac (75 mg in saline solution 0.9% 100 cc) on 1 day, or placebo (saline solution 0.9% 100 cc) on another day. The night before the test the subjects were asked to collect a salivary cortisol and cortisone sample, which was repeated on the night of the procedure session. Serial urine and blood samples were collected on the test day (for osmolality, electrolytes, ACTH, cortisol, copeptin, MR-proADM, MR-proANP; the last three represent more stable and analytically reliable molecules than their respective active peptides). Moreover, the subjects were evaluated with the bioimpedance vector analysis (BIVA) before and after the test. Forty-eight hours after the end of the procedure urine sodium, urine potassium, urine osmolality, serum sodium and copeptin were revaluated together with BIVA. RESULTS: No significant changes in circulating hormone levels were observed; anyway, 48 h after diclofenac, BIVA showed a significant water retention (p < 0.00001), especially in extracellular fluid (ECF) (16.47 ± 1.65 vs 15.67 ± 1.84, p < 0.001). Salivary cortisol and cortisone tended to increase only the night after placebo administration (p = 0.054 cortisol; p = 0.021 cortisone). CONCLUSION: Diclofenac resulted in an increased ECF at 48 h, but this phenomenon seems to be associated with a greater renal sensibility to the action of vasopressin rather than with an increase in its secretion. Moreover, a partial inhibitory effect on cortisol secretion can be hypothesized.

Management of patients with extensive locally advanced thyroid cancer: results of multimodal treatments.

PURPOSE: Surgery plays a key role in the treatment of thyroid cancer (TC) patients. Locally advanced cases, however, can require an extensive surgical approach with technical issues and a high risk of complications. In these cases, a multidisciplinary evaluation should be carried out to evaluate pros and cons. The aim of this study was to share our experience, as a multidisciplinary team, in the management of patients with locally advanced TC with a particularly extensive local disease, whose surgical approach could be challenging and part of a multimodal treatment. METHODS: We retrospectively evaluated clinical, surgical, and oncologic features of all patients with locally advanced TC who had undergone multidisciplinary surgery from January 2019 to June 2020. RESULTS: Six patients (two cases each of poorly differentiated, papillary, and medullary TC) were included. Four out of six were suffering from symptoms related to the advanced disease. At pre-surgical evaluation, a multidisciplinary team proposed extended surgery with radical intent via cervicotomy and sternotomy, considering other therapies not feasible or probably ineffective without it. No one passed away in intra- or perioperative time. At the end of follow-up (median 2.6 years), all patients presented a remission of symptoms due to the advanced disease, four patients were submitted to adjuvant therapies and only one patient died for a cause unrelated to the disease. CONCLUSION: This series of very advanced TCs shows the effectiveness of a surgery performed by a multidisciplinary team in controlling symptoms, allowing adjuvant therapies, and improving the survival of patients whose cases would otherwise be very difficult to manage.

Validation of modular endoscopic medial maxillectomies for inverted papilloma of the maxillary sinus.

BACKGROUND: Treatment of inverted papilloma of the maxillary sinus (IPMS) has a lower success rate compared to other IPs. As such, its correct management generally needs trans-nasal endoscopic medial maxillectomy (EMMs) for adequate resection. The aim of this manuscript is to describe outcomes and major prognostic factors of a cohort of patients with IPMS who were treated with EMM. METHODOLOGY: In this multicentric study, patients affected with IPMS and treated with EMMs were included. The site of origin of the IPMS were studied as well as the type of EMM performed. The histological features (IP vs dysplasia), type of mucosal resection (total vs. pedicle oriented), and post-operative complications were analyzed. RESULTS: 310 patients were included (212 primary and 98 recurrent cases). After a mean follow-up of 45.4 months, 15 patients experienced recurrence (4.8%) due to the application of EMMs tailored to the surgical insertion point. Dysplasia was significantly associated with a higher risk of recurrence. The rates of early and late complications were 11.6% and 11.9%, respectively. CONCLUSIONS: IPMS resection via tailored EMM is associated with excellent disease control, thus excluding the systematic use of extended EMMs, which can however be justified in case of dysplastic IPMS given its significant impact on recurrence.

EPA Consensus Project Paper: The Relationship Between Prosthodontic Rehabilitations and Temporomandibular Disorders.

AIM: The aim of this systematic review is to evaluate the relationship between prosthodontic treatment and temporomandibular disorders (TMD). MATERIALS AND METHODS: Two clinical questions have been raised. Can prosthodontic treatment be used as a strategy to manage temporomandibular disorders? Is there any causal relationship between prosthodontic rehabilitation and the onset of TMD? A systematic search was performed in four medical databases to identify Clinical Trials (CT) and Randomized Clinical Trials (RCT) that could answer the two clinical questions. RESULTS: Any articles fulfilling the inclusion criteria were found. Therefore, the best available evidence on TMD management and aetiology is discussed in a scoping review with focus on the relationship with prosthodontic treatment. CONCLUSIONS: Based on current scientific evidence, prosthetic rehabilitation cannot be proposed as a treatment option for TMD patients, based on the effectiveness of other more conservative options as well as the absence of association between features of dental occlusion and TMD. Thanks to the high neuro plastic adaptation skills of the stomatognathic system, prosthodontic rehabilitation cannot be identified as a direct cause of TMD, but clinicians should pay caution when performing relevant occlusal modifications.

Vaccination strategies for measles control and elimination: time to strengthen local initiatives.

BACKGROUND: Through a combination of strong routine immunization (RI), strategic supplemental immunization activities (SIA) and robust surveillance, numerous countries have been able to approach or achieve measles elimination. The fragility of these achievements has been shown, however, by the resurgence of measles since 2016. We describe trends in routine measles vaccine coverage at national and district level, SIA performance and demographic changes in the three regions with the highest measles burden. FINDINGS: WHO-UNICEF estimates of immunization coverage show that global coverage of the first dose of measles vaccine has stabilized at 85% from 2015 to 19. In 2000, 17 countries in the WHO African and Eastern Mediterranean regions had measles vaccine coverage below 50%, and although all increased coverage by 2019, at a median of 60%, it remained far below levels needed for elimination. Geospatial estimates show many low coverage districts across Africa and much of the Eastern Mediterranean and southeast Asian regions. A large proportion of children unvaccinated for MCV live in conflict-affected areas with remote rural areas and some urban areas also at risk. Countries with low RI coverage use SIAs frequently, yet the ideal timing and target age range for SIAs vary within countries, and the impact of SIAs has often been mitigated by delays or disruptions. SIAs have not been sufficient to achieve or sustain measles elimination in the countries with weakest routine systems. Demographic changes also affect measles transmission, and their variation between and within countries should be incorporated into strategic planning. CONCLUSIONS: Rebuilding services after the COVID-19 pandemic provides a need and an opportunity to increase community engagement in planning and monitoring services. A broader suite of interventions is needed beyond SIAs. Improved methods for tracking coverage at the individual and community level are needed together with enhanced surveillance. Decision-making needs to be decentralized to develop locally-driven, sustainable strategies for measles control and elimination.

Clinical characteristics and outcome of critically ill COVID-19 patients with acute kidney injury: a single centre cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common manifestation among patients critically ill with SARS-CoV-2 infection (Coronavirus 2019) and is associated with significant morbidity and mortality. The pathophysiology of renal failure in this context is not fully understood, but likely to be multifactorial. The intensive care unit outcomes of patients following COVID-19 acute critical illness with associated AKI have not been fully explored. We conducted a cohort study to investigate the risk factors for acute kidney injury in patients admitted to and intensive care unit with COVID-19, its incidence and associated outcomes. METHODS: We reviewed the medical records of all patients admitted to our adult intensive care unit suffering from SARS-CoV-2 infection from 14th March 2020 until 12th May 2020. Acute kidney injury was defined using the Kidney Disease Improving Global Outcome (KDIGO) criteria. The outcome analysis was assessed up to date as 3rd of September 2020. RESULTS: A total of 81 patients admitted during this period. All patients had acute hypoxic respiratory failure and needed either noninvasive or invasive mechanical ventilatory support. Thirty-six patients (44%) had evidence of AKI (Stage I-33%, Stage II-22%, Renal Replacement Therapy (RRT)-44%). All patients with AKI stage III had RRT. Age, diabetes mellitus, immunosuppression, lymphopenia, high D-Dimer levels, increased APACHE II and SOFA scores, invasive mechanical ventilation and use of inotropic or vasopressor support were significantly associated with AKI. The peak AKI was at day 4 and mean duration of RRT was 12.5 days. The mortality was 25% for the AKI group compared to 6.7% in those without AKI. Among those received RRT and survived their illness, the renal function recovery is complete and back to baseline in all patients. CONCLUSION: Acute kidney injury and renal replacement therapy is common in critically ill patients presenting with COVID-19. It is associated with increased severity of illness on admission to ICU, increased mortality and prolonged ICU and hospital length of stay. Recovery of renal function was complete in all survived patients.

The use of outdoor gyms is associated with women and low-income people: a cross-sectional study.

OBJECTIVE: To examine the prevalence, and the demographic, socio-economic, and health correlates to Outdoor Gyms (OGs) use for adults from a southern Brazilian city. STUDY DESIGN: Population-based cross-sectional study. METHODS: A total of 431 adults (66.8% women) aged 18-87 years living in the surroundings of four OGs distributed in different regions of the city were randomly selected. Information about OG use for physical activity (PA) practice, and demographic, socio-economic, and health variables were collected by household interviews. Associations between independent variables and OG use were analyzed with results expressed as odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: About one-third of participants (30.4%; 95% CI: 26.1-34.7) informed using OGs for PA practice, and 20.4% (95% CI 16.8-24.4) informed using it twice or more times a week (≥2x/week). Adjusted analysis indicated that the OG use ≥2x/week is higher for women (OR: 1.93; 95% CI: 1.11-3.35) and for those with lower family income (OR: 2.13; 95% CI: 1.03-4.13) than men and those with higher family income, respectively. CONCLUSION: About 30% of the population uses OGs for PA practice. Women and low-income people are those who more commonly use OGs for PA practice. The installation of these facilities in public spaces may reduce social inequities related to leisure-time PA.

[Short version of the 2nd edition of the German-Austrian S3 guidelines "Cardiogenic shock complicating myocardial infarction-Diagnosis, monitoring and treatment"]. / Kurzversion der 2. Auflage der deutsch-österreichischen S3-Leitlinie "Infarkt-bedingter Kardiogener Schock ­ Diagnose, Monitoring und Therapie".

BACKGROUND: The present guidelines ( http://leitlinien.net ) focus exclusively on cardiogenic shock due to myocardial infarction (infarction-related cardiogenic shock, ICS). The cardiological/cardiac surgical and the intensive care medicine strategies dealt with in these guidelines are essential to the successful treatment and survival of patients with ICS; however, both European and American guidelines on myocardial infarction and heart failure and also position papers on cardiogenic shock focused mainly on cardiological aspects. METHODS: Evidence on the diagnosis, monitoring and treatment of ICS was collected and recommendations compiled in a nominal group process by delegates of the German Cardiac Society (DGK), the German Society for Medical Intensive Care Medicine and Emergency Medicine (DGIIN), the German Society for Thoracic and Cardiovascular Surgery (DGTHG), the German Society for Anaesthesiology and Intensive Care Medicine (DGAI), the Austrian Society for Internal and General Intensive Care Medicine (ÖGIAIM), the Austrian Cardiology Society (ÖKG), the German Society for Prevention and Rehabilitation of Cardiovascular Diseases (DGPR) and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), under the auspices of the Working Group of the Association of Medical Scientific Societies in Germany (AWMF). If only poor evidence on ICS was available, general study results on intensive care patients were inspected and presented in order to enable analogue conclusions. RESULTS: A total of 95 recommendations, including 2 statements were compiled and based on these 7 algorithms with defined instructions on the course of treatment.

Optimal Use of Physical Centric Relation Records for Digital Workflows.

Correctly articulated dental casts are essential for certain dental treatment. Articulation can be traditional: using a physical articulator; digital: using a physical articulator followed by 3D scanning, or virtual: using 3D scanning and software to articulate scans without initial physical articulation. This study compared the precision of traditional articulation, using physical centric relation records and an articulator and virtually, by digitally aligning scans of the casts and record. Articulated casts and centric relation records were obtained. 12 record pairs were recorded from the articulated casts. Virtual method: all records were scanned, unclamped, in a custom laboratory scanner. The casts were aligned to each scanned record to create virtual articulations. Traditional method: each record was used to physically articulate the casts. Each articulation was recorded using an intraoral scanner. The mean inter-arch separation between three key-points on each cast-pair were used to determine differences in occlusal separation in three anatomical directions, and precision of methods. Traditional articulations: standard deviations in key-point distance never exceeded 0.102mm. The virtual equivalent was 0.059mm. Statistically significant differences (p⟨0.05) between all anteroposterior separation distances were found between the methods, and in three of six lateral/vertical separations. Virtual articulation was significantly more precise than traditional articulation.

Effect of prosthetic framework material, cantilever length and opposing arch on peri-implant strain in an all-on-four implant prostheses.

AIM: To evaluate the effect of prosthetic framework material and cantilever length on peri-implant strain in mandibular all-on-four implant-supported prostheses with different types of arch antagonist forces. MATERIALS AND METHODS: Models simulating a completely edentulous mandibular arch fabricated in heat-cured acrylic resin were used. On the acrylic models, four implants were placed at regions 34, 32, 42, and 44 simulating all-on-four implant placements. Implant-supported screw-retained fixed prosthesis frameworks were fabricated using three different materials (cobalt-chromium, zirconia, and polyetheretherketone) and with three different cantilever lengths (zero mm, 15 mm, and 25 mm). Strain gauges were attached on the model at the buccal and lingual positions of each implant. Forces simulating opposing natural dentition, conventional complete denture, and the parafunctional habit were applied to the models. The peri-implant strain in each strain gauge was recorded. RESULTS: Least peri-implant strains (67 microstrains) were observed when forces simulating conventional complete dentures were applied on the models and the highest peri-implant strains (9091 microstrains) were observed when forces simulating parafunctional habit were applied. One-way ANOVA test followed by Tukey's post hoc analysis was performed to compare the mean deformation scores between different materials at 50 N load. The level of significance [P-value] was set at P < 0.05. Tests showed significant differences between zero mm and the other types in all the different materials, and also between 1.5 x AP and 2.5 x AP for Zirconia and Peek material at P = 0.02 & P = .008, respectively. The results showed that the type of framework material, cantilever length, and occlusal forces from the opposing arch influence the peri-implant strain in the bone in all-on-four implant-supported prostheses. CONCLUSION: Rehabilitation of a single, completely edentulous arch with implant-supported prostheses should consider the situation of the opposing arch. The choice of framework material, as well as the cantilever length, should be altered based on the forces from the opposing arch.

Generation of a neutralizing antibody against RD114-pseudotyped viral vectors.

The feline endogenous RD114 glycoprotein has proved to be an attractive envelope to pseudotype both retroviral and lentiviral vectors. As a surface protein, its detection on packaging cells as well as viral particles would be useful in different fields of its use. To address this, we generated a monoclonal antibody against RD114 by immunization of rats, termed 22F10. Once seroconversion was confirmed, purified 22F10 was cloned into murine Fc and characterized with a binding affinity of 10nM. The antibody was used to detect RD114 and its variant envelopes on different stable viral packaging cell lines (FLYRD18 and WinPac-RD). 22F10 was also shown to prevent the infections of different strains of RD-pseudotyped vectors but not related envelope glycoproteins by blocking cell surface receptor binding. We are the first to report the neutralization of viral particles by a monoclonal αRD114 antibody.

Correction to: Oxidative stress and Nrf2 expression in peripheral blood mononuclear cells derived from COPD patients: an observational longitudinal study.

An amendment to this paper has been published and can be accessed via the original article.

Oxidative stress and Nrf2 expression in peripheral blood mononuclear cells derived from COPD patients: an observational longitudinal study.

BACKGROUND: A persistent low inflammatory-oxidative status and the inadequacy of the antioxidant nuclear factor-E2-related factor 2 (Nrf2) have been implicated in chronic obstructive pulmonary disease (COPD) progression. Therefore this study was aimed to assess the association between lung function decline and oxidative-inflammatory markers and Nrf2 signaling pathway expression in peripheral blood mononuclear cells (PBMCs) over time. METHODS: 33 mild-moderate COPD outpatients (mean age 66.9 ± 6.9 years) were age-sex matched with 37 no-COPD subjects. A clinical evaluation, blood sampling tests and a spirometry were performed at baseline and after a mean follow-up of 49.7 ± 6.9 months. RESULTS: In COPD, compared to no-COPD, we found a faster lung function decline at follow-up. Although similar prevalence of smoking, hypertension, diabetes and dyslipidemia, systemic markers of inflammation (hs-CRP and white blood cells, WBCs) and oxidative stress (8-isoprostane) were significantly increased in COPD at follow-up, while the antioxidant glutathione (GSH) was significantly reduced. Moreover the expression of Nrf2 and of Nrf2-related genes heme oxygenase (HO)-1 and glutamate-cysteine ligase catalytic (GCLC) subunit in PBMCS were significantly down-regulated in COPD at follow-up, whereas no changes were observed in no-COPD. The percent variation (Δ) of FEV1 detected after the follow-up in COPD patients was directly correlated with ΔNrf2 (r = 0.826 p < 0.001), ΔHO-1 (r = 0.820, p < 0.001) and ΔGCLC (r = 0.840, p < 0.001). Moreover ΔFEV1 was also directly correlated with ΔGSH (r = 0.595, p < 0.01) and inversely correlated with Δ8-iso (r = - 0.587, p < 0.01) and with baseline smoking history (r = - 0.39, p < 0.03). No correlation was found between ΔFEV1, ΔCRP and ΔWBCs. By means of hierarchical stepwise multiple linear regression, taking into account other baseline key factors related to FEV1, ΔNrf2, ΔHO-1and ΔGCLC were found to be significant predictors of ΔFEV1, explaining 89.5% of its variance. CONCLUSIONS: Although our results must be confirmed in larger trial they suggest that the down-regulation of Nrf2/ARE gene expression in PBMCs may be one of the determinants of FEV1 decline and of COPD progression. Therefore the future possibility to counteract Nrf2 decline in COPD patients may help in reducing the negative effects of the oxidative stress-induced progression of the disease.

Predictive value of the sentinel lymph node procedure in the staging of non-metastatic colorectal cancer.

PURPOSE: Despite the recent growing interest of the scientific community, there is still no consensus on the actual applicability and effectiveness of sentinel lymph node (SL) procedure in colon cancers. This study aims to quantify feasibility, detection rate, negative predictive value, and accuracy of the SL identified with fluorescent dye in early colon cancers (ECC). METHODS: This study conducted a consecutive sampling of 95 patients with non-metastatic colorectal cancer who have been treated with laparoscopic colon resection and complete mesocolic excision after a 25-mg indocyanine green peritumoral laparoscopic injection and SL identification with a near-infrared camera. The SL was later isolated and sent to ultra-staging. RESULTS: Ninety-five patients with an average age of 71 (range 37-90) and a mean BMI of 25 (range 18-39) have been recruited. On the patient sample (92 Pts), an average of 1.49 SL (range 1-5) and a mean time of 4 min were identified. The detection rate was 96.8% and the negative predictive value and accuracy rates were 96.2% and 93.4%, respectively. CONCLUSIONS: Mapping the SL with fluorescent dye can play an important role in the treatment of colon cancers, particularly those at early stages, and can lead to ultra-conservative surgery.

Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small vessel disease caused by C-terminal truncating TREX1 mutations. The disease is typically characterized by vascular retinopathy and focal and global brain dysfunction. Systemic manifestations have also been reported but not yet systematically investigated. METHODS: In a cross-sectional study, we compared the clinical characteristics of 33 TREX1 mutation carriers (MC+) from three Dutch RVCL-S families with those of 37 family members without TREX1 mutation (MC-). All participants were investigated using personal interviews, questionnaires, physical, neurological and neuropsychological examinations, blood and urine tests, and brain MRI. RESULTS: In MC+, vascular retinopathy and Raynaud's phenomenon were the earliest symptoms presenting from age 20 onwards. Kidney disease became manifest from around age 35, followed by liver disease, anaemia, markers of inflammation and, in some MC+, migraine and subclinical hypothyroidism, all from age 40. Cerebral deficits usually started mildly around age 50, associated with white matter and intracerebral mass lesions, and becoming severe around age 60-65. CONCLUSIONS: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare, but likely underdiagnosed, systemic small vessel disease typically starting with vascular retinopathy, followed by multiple internal organ disease, progressive brain dysfunction, and ultimately premature death.

Coral degradation alters predator odour signatures and influences prey learning and survival.

Habitat degradation is a key factor leading to the global loss of biodiversity. This problem is particularly acute in coral reef ecosystems. We investigated whether recognition of predator odours by damselfish was influenced by coral degradation and whether these changes altered survival in the wild. We taught whitespot damselfish to recognize the odour of a predator in the presence of live/healthy coral or dead/degraded coral. Fish were tested for a response to predator odours in environments that matched their conditioning environment or in environments that were mismatched. Next, we taught blue damselfish to recognize the odour of three common reef predators in live and degraded coral environments and then stocked them onto live or degraded patch reefs, where we monitored their subsequent response to predator odour along with their survival. Damselfish learned to recognize predator odours in both coral environments, but the intensity of their antipredator response was much greater when the conditioning and test environments matched. Fish released on degraded coral had about 50% higher survival if they had been trained in the presence of degraded coral rather than live coral. Altering the intensity of antipredator responses could have rather profound consequences on population growth.

Alcoholic beverages as trigger factor and the effect on alcohol consumption behavior in patients with migraine.

BACKGROUND AND PURPOSE: Alcoholic beverages are frequently reported migraine triggers. We aimed to assess self-reported alcohol consumption as a migraine attack trigger and to investigate the effect on alcohol consumption behavior in a large migraine cohort. METHODS: We conducted a cross-sectional, web-based, questionnaire study among 2197 patients with migraine from the well-defined Leiden University MIgraine Neuro-Analysis (LUMINA) study population. We assessed alcoholic beverage consumption and self-reported trigger potential, reasons behind alcohol abstinence and time between alcohol consumption and migraine attack onset. RESULTS: Alcoholic beverages were reported as a trigger by 35.6% of participants with migraine. In addition, over 25% of patients with migraine who had stopped consuming or never consumed alcoholic beverages did so because of presumed trigger effects. Wine, especially red wine (77.8% of participants), was recognized as the most common trigger among the alcoholic beverages. However, red wine consistently led to an attack in only 8.8% of participants. Time of onset was rapid (<3 h) in one-third of patients and almost 90% had an onset <10 h independent of beverage type. CONCLUSIONS: Alcoholic beverages, especially red wine, are recognized as a migraine trigger factor by patients with migraine and have a substantial effect on alcohol consumption behavior. Rapid onset of provoked migraine attacks in contrast to what is known about hangover headache might point to a different mechanism. The low consistency of provocation suggests that alcoholic beverages acting as a singular trigger is insufficient and may depend on a fluctuating trigger threshold.

The use of only enamel matrix derivative allows outstanding regeneration results in periodontal intrabony defect treatment: a retrospective study.

Periodontal tissue regeneration depends on several biological, homeostatic and regulative variables that directly induce the clinical features. The aim of this study is to compare the clinical results obtained using the enamel matrix derivative peptide (EMP) compared to the less manageable association of EMP and bovine bone xenographic (BPBM) in the treatment of deep intraosseous defects. Ten healthy patients, suffering from moderate or severe chronic periodontitis, having at least two deep and narrow intrabony defects in the same dental arch and needing surgical treatment, were selected. The same patient was treated with the two different materials: EMP -TG1 in one defect and the association-TG2 in the other. Immediately before surgery (T0) and 12-month after (T2) the probing depth (PD) and gingival recession (GR) were registered at the experimental sites. No statistically significant differences were shown between TG1 and TG2 at T0 nor at T1 in term of PD and GR, while a statistically significant PD decrease was found both in TG1 and TG2 between T0 and T1 (p less than 0.05). GR increase resulted statistically significant in TG1 (p less than 0.05) but not in TG2 between T0 and T1 (p≥0.05). In this split-mouth retrospective study, both the treatments achieve favourable clinical results but the TG1 shows a significant increase in GR probably because EMP is not able to support the gingiva covering the intrabony defect. Therefore, the choice of the type of periodontal defect to be treated with EMP will be a therapeutic key-point.

Polymer ultrapermeability from the inefficient packing of 2D chains.

The promise of ultrapermeable polymers, such as poly(trimethylsilylpropyne) (PTMSP), for reducing the size and increasing the efficiency of membranes for gas separations remains unfulfilled due to their poor selectivity. We report an ultrapermeable polymer of intrinsic microporosity (PIM-TMN-Trip) that is substantially more selective than PTMSP. From molecular simulations and experimental measurement we find that the inefficient packing of the two-dimensional (2D) chains of PIM-TMN-Trip generates a high concentration of both small (<0.7 nm) and large (0.7-1.0 nm) micropores, the former enhancing selectivity and the latter permeability. Gas permeability data for PIM-TMN-Trip surpass the 2008 Robeson upper bounds for O2/N2, H2/N2, CO2/N2, H2/CH4 and CO2/CH4, with the potential for biogas purification and carbon capture demonstrated for relevant gas mixtures. Comparisons between PIM-TMN-Trip and structurally similar polymers with three-dimensional (3D) contorted chains confirm that its additional intrinsic microporosity is generated from the awkward packing of its 2D polymer chains in a 3D amorphous solid. This strategy of shape-directed packing of chains of microporous polymers may be applied to other rigid polymers for gas separations.