Amplifying the Noise: Oncometabolites Mask an Epigenetic Signal of DNA Damage.

A recent study (Sulkowski et al., 2020) reveals that oncometabolites, which are produced by metabolic gene mutations in many cancers, sensitize cells to PARP inhibition by antagonizing histone demethylation and obscuring epigenetic marks that are necessary for efficient DNA repair.

Mutagenesis enhances gellan gum production by a novel Sphingomonas spp.: upstream optimization, kinetic modeling, and structural and physico-functional evaluation.

Gellan gum (GG) has gained tremendous attention owing to its diversified applications. However, its high production and hence market cost are still a bottleneck in its widespread utilization. In the present study, high GG producing mutant of Sphingomonas spp. was developed by random mutagenesis using ethyl methylsulphonate (EMS) for industrial fermentation and identified as Sphingomonas trueperi after 16S rRNA and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) analysis. The fermentation conditions such as pH, temperature, and inoculum ratio were optimized by one factor at a time (OFAT) followed by screening of medium components by the Plackett-Burman statistical design. The most critical nutrients were further optimized by response surface methodology for maximizing GG production. The effect of dissolved oxygen tension in bioreactor on cell growth, substrate consumption, GG production, and batch productivity was elucidated. The highest GG titer (23 ± 2.4 g/L) was attained in optimized medium at 10% inoculum (6.45 ± 0.5 log cfu/mL) under controlled fermentation conditions of pH (7), temperature (30 °C), agitation (300-600 rpm), and aeration (0.5-2.0 SLPM) at 22 ± 2% dissolved oxygen tension in a 10-L bioreactor. Kinetic modeling of optimized batch process revealed that logistic growth model could best explain biomass accumulation, while GG formation and substrate consumption were best explained by Luedeking-Piret and exponential decay model, respectively. Structural and physico-functional features of GG produced by mutant Sphingomonas spp. were characterized by HPLC, FTIR, NMR, DSC, TGA, GPC, SEM, and rheological analysis. The higher productivity (0.51 g/L/h) under optimized fermentation conditions suggests potential consideration of mutant and process for commercial utilization.

Immune response induced by a Streptococcus suis multi-serotype autogenous vaccine used in sows to protect post-weaned piglets.

Streptococcus suis is a bacterial pathogen that causes important economic losses to the swine industry worldwide. Since there are no current commercial vaccines, the use of autogenous vaccines applied to gilts/sows to enhance transfer of passive immunity is an attractive alternative to protect weaned piglets. However, there is no universal standardization in the production of autogenous vaccines and the vaccine formulation may be highly different among licenced manufacturing laboratories. In the present study, an autogenous vaccine that included S. suis serotypes 2, 1/2, 5, 7 and 14 was prepared by a licensed laboratory and administrated to gilts using a three-dose program prior to farrowing. The antibody response in gilts as well as the passive transfer of antibodies to piglets was then evaluated. In divergence with previously published data with an autogenous vaccine produced by a different company, the increased response seen in gilts was sufficient to improve maternal antibody transfer to piglets up to 5 weeks of age. However, piglets would still remain susceptible to S. suis disease which often appears during the second part of the nursery period. Vaccination did not affect the shedding of S. suis (as well as that of the specific S. suis serotypes included in the vaccine) by either gilts or piglets. Although all antibiotic treatments were absent during the trial, the clinical protective effect of the vaccination program with the autogenous vaccine could not be evaluated, since limited S. suis cases were present during the trial, confirming the need for a complete evaluation of the clinical protection that must include laboratory confirmation of the aetiological agent involved in the presence of S. suis-associated clinical signs. Further studies to evaluate the usefulness of gilt/sow vaccination with autogenous vaccines to protect nursery piglets should be done.

Alterations in Swallowing Six Weeks After Primary Anterior Cervical Discectomy and Fusion (ACDF).

This aim of this study is to characterize the nature and pathophysiology of dysphagia after ACDF surgery by precisely and comprehensively capturing within-subject changes on videofluoroscopy between preoperative and postoperative time points. 21 adults undergoing planned primary ACDF procedures were prospectively recruited and enrolled. Participants underwent standardized preoperative and six-week postoperative videofluoroscopic swallow studies. Videos were blindly rated using the Penetration-Aspiration Scale (PAS) and analysis of total pharyngeal residue (%C2-42), swallowing timing, kinematics, and anatomic change was completed. Linear mixed-effects modeling was used to explore the relationships between possible predictor variables and functional outcomes of interest that changed across timepoints. There was no change in PAS scores across timepoints. Total pharyngeal residue (%C2-C42) was increased postoperatively (p < 0.001). Our statistical model revealed significant main effects for timepoint (p = 0.002), maximum pharyngeal constriction area (MPCAN) (p < 0.001), and maximum thickness of posterior pharyngeal (PPWTMAX) (p = 0.004) on the expression of total pharyngeal residue. There were significant two-way interactions for timepoint and MPCAN (p = 0.028), timepoint and PPWTMAX (p = 0.005), and MPCAN and PPWTMAX (p = 0.010). Unsurprisingly, we found a significant three-way interaction between these three predictors (p = 0.027). Our findings suggest that in planned ACDF procedures without known complications, swallowing efficiency is more likely to be impaired than airway protection six weeks after surgery. The manifestation of impaired swallowing efficiency at this timepoint appears to be driven by a complex relationship between reduced pharyngeal constriction and increased prevertebral edema.

A scoping review of the methods used to capture dysphagia after anterior cervical discectomy and fusion: the need for a paradigm shift.

OBJECTIVE: Dysphagia is the most commonly reported complication of annterior cervical discectomy and fusion (ACDF) surgery. However, the incidence of dysphagia post-ACDF varies widely-partly attributable to differing outcome measures used to capture dysphagia. Our objective was to conduct a scoping review of the literature to quantify which dysphagia outcome measures have been employed post-ACDF and examine trends by study design, year, and location. METHODS: After removing duplicates, 2396 abstracts were screened for inclusion. A total of 480 studies were eligible for full-text review. After applying exclusion criteria, data was extracted from 280 studies. We extracted the dysphagia outcome measure(s), study design (prospective vs retrospective), year, and location (country). Approximately 10% of studies were repeated for intra-rater agreement. RESULTS: In total, 317 dysphagia outcome measures were reported in 280 studies (primarily retrospective-63%). The largest proportion of outcome measures were categorized as "unvalidated patient-reported outcome measures" (46%), largely driven by use of the popular Bazaz scale. The next most common categories were "insufficient detail" and "validated patient-reported outcome measures" (both 16%) followed by "chart review/database" (13%) and instrumental assessment (7%). Studies examining dysphagia post-ACDF steadily increased over the years and the use of validated measures increased in the past 10 years. CONCLUSIONS: This scoping review of the literature highlights that nearly half of the ACDF dysphagia literature relies on unvalidated patient-reported outcome measures. The current understanding of the mechanism, timeline, and presentation of dysphagia post-ACDF are likely limited due to the metrics that are most commonly reported in the literature.

Mannosylated Systems for Targeted Delivery of Antibacterial Drugs to Activated Macrophages.

Macrophages are a promising target for drug delivery to influence macrophage-associated processes in the body, namely due to the presence of resistant microorganisms in macrophages. In this work, a series of mannosylated carriers based on mannan, polyethylenimine (PEI) and cyclodextrin (CD) was synthesized. The molecular architecture was studied using FTIR and 1H NMR spectroscopy. The particle size, from small 10-50 nm to large 500 nm, depending on the type of carrier, is potentially applicable for the creation of various medicinal forms: intravenous, oral and inhalation. Non-specific capture by cells with a simultaneous increase in selectivity to CD206+ macrophages was achieved. ConA was used as a model mannose receptor, binding galactosylated (CD206 non-specific) carriers with constants of the order of 104 M-1 and mannosylated conjugates of 106-107 M-1. The results of such primary "ConA-screening" of ligands are in a good agreement in terms of the comparative effectiveness of the interaction of ligands with the CD206+ macrophages: non-specific (up to 10%) absorption of highly charged and small particles; weakly specific uptake of galactosylated polymers (up to 50%); and high affine capture (more than 70-80%) of the ligands with grafted trimannoside was demonstrated using the cytometry method. Double and multi-complexes of antibacterials (moxifloxacin with its adjuvants from the class of terpenoids) were proposed as enhanced forms against resistant pathogens. In vivo pharmacokinetic experiments have shown that polymeric carriers significantly improve the efficiency of the antibiotic: the half-life of moxifloxacin is increased by 2-3 times in conjugate-loaded forms, bio-distribution to the lungs in the first hours after administration of the drug is noticeably greater, and, after 4 h of observation, free moxifloxacin was practically removed from the lungs of rats. Although, in polymer systems, its content is significant-1.2 µg/g. Moreover, the importance of the covalent crosslinking carrier with mannose label was demonstrated. Thus, this paper describes experimental, scientifically based methods of targeted drug delivery to macrophages to create enhanced medicinal forms.

Mechanical and Contractile Properties of Knee Joint Muscles Measured by the Method of Tensiomyography in Differently Trained Men and Women.

ABSTRACT: Toskic, LD, Dopsaj, MJ, Markovic, MR, Toskic, DR, Ignjatovic, AM. Mechanical and contractile properties of knee joint muscles measured by the method of tensiomyography in differently trained men and women. J Strength Cond Res 36(6): 1532-1539, 2022-The aim of this study was to investigate the differences in mechanical and contractile properties of knee joint flexor and extensor muscles between differently trained men and women, using tensiomyography (TMG). The sample consisted of 159 subjects (84 men and 75 women), who were assigned to one of 5 groups according to the following levels and types of their physical activity: physically inactive, physically active nonathletes, strength and power athletes, endurance athletes, and team sports athletes. Measurements were performed on the following knee flexor and extensor muscles of the dominant leg: rectus femoris, vastus medialis, vastus lateralis, biceps femoris, and semitendinosus. The results showed significant differences in contraction time-Tc (F = 1.911, p = 0.010) and delay time-Td (F = 1.989, p = 0.007) parameters between differently trained men and women, whereas in other TMG parameters, there were no differences between groups. It is indicated that physical activities characteristic of strength and power sports (combat sports and sprint disciplines) could lead to an increased speed of twitch force generation and fast twitch muscle fibers, and that almost any regular, systematic, and planned physical activity leads to increased muscle responsiveness. Obtained results also indicated that TMG parameters do not have enough specific discriminatory power for detecting differences between differently trained young adults.

PPARα agonist fenofibrate attenuates iron-induced liver injury in mice by modulating the Sirt3 and ß-catenin signaling.

Iron accumulation is frequently associated with chronic liver diseases. However, our knowledge on how iron contributes to the liver injury is limited. Aberrant Wnt/ß-catenin signaling is a hallmark of several hepatic pathologies. We recently reported that peroxisome proliferator-activated receptor α (PPARα) agonist, fenofibrate, prevents iron-induced oxidative stress and ß-catenin signaling by chelating the iron. Sirtuin3 (Sirt3), a type of NAD+-dependent deacetylase, that plays a critical role in metabolic regulation was found to prevent ischemia reperfusion injury (IRI) by normalizing the Wnt/ß-catenin pathway. In the present study, we explored if fenofibrate prevents iron-induced liver injury by regulating the Sirt3 and ß-catenin signaling. In vitro and in vivo iron treatment resulted in the downregulation of PPARα, Sirt3, active ß-catenin, and its downstream target gene c-Myc in the mouse liver. Pharmacological activation of Sirt3, both in vitro and in vivo, by Honokiol (HK), a known activator of Sirt3, abrogated the inhibitory effect of iron overload on active ß-catenin expression and prevented the iron-induced upregulation of α smooth muscle actin (αSMA) and TGFß expression. Intrinsically, PPARα knockout mice showed significant downregulation of hepatic Sirt3 levels. In addition, treatment of iron overload mice with PPARα agonist fenofibrate reduced hepatic iron accumulation and prevented iron-induced downregulation of liver Sirt3 and active ß-catenin, mitigating the progression of fibrosis. Thus, our results establish a novel link between hepatic iron and PPARα, Sirt3, and ß-catenin signaling. Further exploration on the mechanisms by which fenofibrate ameliorates iron-induced liver injury likely has significant therapeutic impact on iron-associated chronic liver diseases.NEW & NOTEWORTHY Hepatic intracellular iron accumulation has been implicated in the pathophysiology of chronic liver diseases. In this study, we identified a novel mechanism involved in the progression of fibrosis. Excess iron accumulation in liver caused downregulation of PPARα-Sirt3-Wnt signaling leading to fibrosis. This work has significant translational potential as PPARα agonist fenofibrate could be an attractive therapeutic drug for the treatment of liver disorders associated with iron overload.

Percutaneous Dilational Tracheostomy for Coronavirus Disease 2019 Patients Requiring Mechanical Ventilation.

OBJECTIVES: To assess the impact of percutaneous dilational tracheostomy in coronavirus disease 2019 patients requiring mechanical ventilation and the risk for healthcare providers. DESIGN: Prospective cohort study; patients were enrolled between March 11, and April 29, 2020. The date of final follow-up was July 30, 2020. We used a propensity score matching approach to compare outcomes. Study outcomes were formulated before data collection and analysis. SETTING: Critical care units at two large metropolitan hospitals in New York City. PATIENTS: Five-hundred forty-one patients with confirmed severe coronavirus disease 2019 respiratory failure requiring mechanical ventilation. INTERVENTIONS: Bedside percutaneous dilational tracheostomy with modified visualization and ventilation. MEASUREMENTS AND MAIN RESULTS: Required time for discontinuation off mechanical ventilation, total length of hospitalization, and overall patient survival. Of the 541 patients, 394 patients were eligible for a tracheostomy. One-hundred sixteen were early percutaneous dilational tracheostomies with median time of 9 days after initiation of mechanical ventilation (interquartile range, 7-12 d), whereas 89 were late percutaneous dilational tracheostomies with a median time of 19 days after initiation of mechanical ventilation (interquartile range, 16-24 d). Compared with patients with no tracheostomy, patients with an early percutaneous dilational tracheostomy had a higher probability of discontinuation from mechanical ventilation (absolute difference, 30%; p < 0.001; hazard ratio for successful discontinuation, 2.8; 95% CI, 1.34-5.84; p = 0.006) and a lower mortality (absolute difference, 34%, p < 0.001; hazard ratio for death, 0.11; 95% CI, 0.06-0.22; p < 0.001). Compared with patients with late percutaneous dilational tracheostomy, patients with early percutaneous dilational tracheostomy had higher discontinuation rates from mechanical ventilation (absolute difference 7%; p < 0.35; hazard ratio for successful discontinuation, 1.53; 95% CI, 1.01-2.3; p = 0.04) and had a shorter median duration of mechanical ventilation in survivors (absolute difference, -15 d; p < 0.001). None of the healthcare providers who performed all the percutaneous dilational tracheostomies procedures had clinical symptoms or any positive laboratory test for severe acute respiratory syndrome coronavirus 2 infection. CONCLUSIONS: In coronavirus disease 2019 patients on mechanical ventilation, an early modified percutaneous dilational tracheostomy was safe for patients and healthcare providers and associated with improved clinical outcomes.

Caregiver burden in patients with behavioural variant frontotemporal dementia and non-fluent variant and semantic variant primary progressive aphasia.

Studies on caregiver burden in patients with frontotemporal lobar degeneration are rare, differ methodologically and show variable results. Single center longitudinal pilot study on caregiver burden and potential risk factors in patients with behavioural variant frontotemporal dementia (bvFTD) and semantic (svPPA) and non-fluent variants (nfvPPA) primary progressive aphasia. Forty-six bvFTD, nine svPPA, and six nfvPPA patients and caring relatives were analysed for up to 2 years using the Mini-Mental State Examination as global measure for cognitive performance, Frontal Assessment Battery (frontal lobe functions), Frontal Behavioural Inventory (personality and behaviour), Neuropsychiatric Inventory (dementia-related neuropsychiatric symptoms), Barthel Index and Lawton IADL Scale (basic and instrumental activities of daily living), the Caregiver Strain Index (CSI), and in most participants also the Zarit Burden Interview (ZBI). CSI baseline sum scores were highest in bvFTD (mean ± SD 5.5 ± 3.4, median 5, IQR 6), intermediate in svPPA (2.9 ± 2.3; 3; 3.5) and low in nfvPPA (1.6 ± 2.1; 1; 2). Similar differences of caregiver burden were found using the ZBI. During follow-up, CSI and ZBI sum scores deteriorated in svPPA, not in bvFTD and nfvPPA, and correlated significantly with personality and behaviour, neuropsychiatric symptoms, caregiver age, and instrumental, but not basic activities of daily living, Mini-Mental State Examination scores or frontal lobe functions. This study reveals differences in caregiver burden in variants of frontotemporal lobar degeneration. Caregivers should be systematically asked for caregiver burden from the time of the diagnosis to provide comprehensive support in time.

Experimental evaluation of protection and immunogenicity of Streptococcus suis bacterin-based vaccines formulated with different commercial adjuvants in weaned piglets.

Streptococcus suis is an important swine pathogen responsible for economic losses to the swine industry worldwide. There is no effective commercial vaccine against S. suis. The use of autogenous ("bacterin") vaccines to control S. suis outbreaks is a frequent preventive measure in the field, although scientific data on immunogenicity and reduction in mortality and morbidity are scarce. The goal of our study is to experimentally evaluate the immunogenicity and protective efficacy against homologous challenge in weaned piglets of a S. suis serotype 2 bacterin-based vaccine formulated with six different commercial adjuvants (Alhydrogel®, Emulsigen®-D, Quil-A®, Montanide™ ISA 206 VG, Montanide™ ISA 61 VG, and Montanide™ ISA 201 VG). The vaccine formulated with Montanide™ ISA 61 VG induced a significant increase in anti-S. suis antibodies, including both IgG1 and IgG2 subclasses, protected against mortality and significantly reduced morbidity and severity of clinical signs. Vaccines formulated with Montanide ISA 206 VG or Montanide ISA 201 VG also induced a significant increase in anti-S. suis antibodies and showed partial protection and reduction of clinical signs severity. Vaccines formulated with Alhydrogel®, Emulsigen®-D, or Quil-A® induced a low and IgG1-shifted antibody response and failed to protect vaccinated piglets against a homologous challenge. In conclusion, the type of adjuvant used in the vaccine formulation significantly influenced the immune response and efficacy of the vaccine against a homologous challenge.

Review of the speculative role of co-infections in Streptococcus suis-associated diseases in pigs.

Streptococcus suis is one of the most important bacterial swine pathogens affecting post-weaned piglets, causing mainly meningitis, arthritis and sudden death. It not only results in severe economic losses but also raises concerns over animal welfare and antimicrobial resistance and remains an important zoonotic agent in some countries. The definition and diagnosis of S. suis-associated diseases can be complex. Should S. suis be considered a primary or secondary pathogen? The situation is further complicated when referring to respiratory disease, since the pathogen has historically been considered as a secondary pathogen within the porcine respiratory disease complex (PRDC). Is S. suis a respiratory or strictly systemic pathogen? S. suis is a normal inhabitant of the upper respiratory tract, and the presence of potentially virulent strains alone does not guarantee the appearance of clinical signs. Within this unclear context, it has been largely proposed that co-infection with some viral and bacterial pathogens can significantly influence the severity of S. suis-associated diseases and may be the key to understanding how the infection behaves in the field. In this review, we critically addressed studies reporting an epidemiological link (mixed infections or presence of more than one pathogen at the same time), as well as in vitro and in vivo studies of co-infection of S. suis with other pathogens and discussed their limitations and possibilities for improvement and proposed recommendations for future studies.

Neurophysiology of epidurally evoked spinal cord reflexes in clinically motor-complete posttraumatic spinal cord injury.

Increased use of epidural Spinal Cord Stimulation (eSCS) for the rehabilitation of spinal cord injury (SCI) has highlighted the need for a greater understanding of the properties of reflex circuits in the isolated spinal cord, particularly in response to repetitive stimulation. Here, we investigate the frequency-dependence of modulation of short- and long-latency EMG responses of lower limb muscles in patients with SCI at rest. Single stimuli could evoke short-latency responses as well as long-latency (likely polysynaptic) responses. The short-latency component was enhanced at low frequencies and declined at higher rates. In all muscles, the effects of eSCS were more complex if polysynaptic activity was elicited, making the motor output become an active process expressed either as suppression, tonic or rhythmical activity. The polysynaptic activity threshold is not constant and might vary with different stimulation frequencies, which speaks for its temporal dependency. Polysynaptic components can be observed as direct responses, neuromodulation of monosynaptic responses or driving the muscle activity by themselves, depending on the frequency level. We suggest that the presence of polysynaptic activity could be a potential predictor for appropriate stimulation conditions. This work studies the complex behaviour of spinal circuits deprived of voluntary motor control from the brain and in the absence of any other inputs. This is done by describing the monosynaptic responses, polysynaptic activity, and its interaction through its input-output interaction with sustain stimulation that, unlike single stimuli used to study the reflex pathway, can strongly influence the interneuron circuitry and reveal a broader spectrum of connectivity.

Long-term intubation and high rate of tracheostomy in COVID-19 patients might determine an unprecedented increase of airway stenoses: a call to action from the European Laryngological Society.

INTRODUCTION: The novel Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, may need intensive care unit (ICU) admission in up to 12% of all positive cases for massive interstitial pneumonia, with possible long-term endotracheal intubation for mechanical ventilation and subsequent tracheostomy. The most common airway-related complications of such ICU maneuvers are laryngotracheal granulomas, webs, stenosis, malacia and, less commonly, tracheal necrosis with tracheo-esophageal or tracheo-arterial fistulae. MATERIALS AND METHODS: This paper gathers the opinions of experts of the Laryngotracheal Stenosis Committee of the European Laryngological Society, with the aim of alerting the medical community about the possible rise in number of COVID-19-related laryngotracheal stenosis (LTS), and the aspiration of paving the way to a more rationale concentration of these cases within referral specialist airway centers. RESULTS: A range of prevention strategies, diagnostic work-up, and therapeutic approaches are reported and framed within the COVID-19 pandemic context. CONCLUSIONS: One of the most important roles of otolaryngologists when encountering airway-related signs and symptoms in patients with previous ICU hospitalization for COVID-19 is to maintain a high level of suspicion for LTS development, and share it with colleagues and other health care professionals. Such a condition requires specific expertise and should be comprehensively managed in tertiary referral centers.

Ultrasound Examination of the Pupil - A New Tool for the Neuro-Ophthalmological Assessment.

BACKGROUND: Pupil examination represents a diagnostic and prognostic test in the management of several neurological diseases. Infrared video pupillometry (IVP) is the gold standard, since it is not routinely available, a noninvasive bedside ultrasound assessment has been proposed as an alternative. The aim of this study was to assess the feasibility and reproducibility of ultrasound pupillometry (UP) in comparison with IVP. MATERIALS AND METHODS: 81 subjects (43 men and 38 women, mean age: 52 ±â€Š20 years and 49 ±â€Š19 years, respectively) with no history of neurophthalmologic disease were enrolled. UP was performed with a 12-MHz linear probe according to current guidelines for orbital insonation. Light and painful stimuli were applied to test pupillary light reflex (PLR) and ciliospinal reflex (CR). In 30 of these subjects IVP examination was performed additionally to obtain intra-observer and inter-observer agreement. RESULTS: Increasing age was associated with a decreased pupillary diameter (PD) at rest, after PLR and CR (R -0.728, p < 0.01, R -0.643, p < 0.01, R 0.674, p < 0.001 respectively), while no association was noticed with time to constriction/dilation. UP measurements were reproducible (rate of inter- and intra-observer agreement: R 0.979, p < 0.01, R 0.946, p < 0.01 respectively) and concordant with IVP (PLR R 0.831, p < 0.01; CR R 0.879, p < 0.01). CONCLUSION: According to our study, ultrasound pupillometry is a feasible and reliable technique for bedside pupillary function assessment, and is a good alternative to infrared video pupillometry. Moreover, it represents the only way for functional pupillary assessment in patients with periorbital hematoma.

Randomized Controlled Comparison of Optimal Medical Therapy with Percutaneous Recanalization of Chronic Total Occlusion (COMET-CTO).

The aim of this randomized prospective study was to evaluate the quality of life (QoL) using the "Seattle Angina Questionnaire" (SAQ) in patients with chronic total occlusion (CTO) in coronary arteries treated with either percutaneous coronary intervention (PCI) or optimal medical therapy (OMT), or only with OMT.The potential benefits of recanalization of CTO by PCI have been controversial because of the scarcity of randomized controlled trials.A total of 100 patients with CTO were randomized (1:1) prospectively into the PCI CTO or the OMT group (50 patients in each group). There were no baseline differences in the SAQ scores between the groups, except for physical limitation scores (P = 0.03). During the mean follow-up (FUP) of 275 ± 88 days, patients in the PCI group reported less physical activity limitations (72.7 ± 21.3 versus 60.5 ± 27, P = 0.014), less frequent angina episodes (89.8 ± 17.6 versus 76.8 ± 27.1, P = 0.006), better QoL (79.9 ± 22.7 versus 62.5 ± 25.5, P = 0.001), greater treatment satisfaction (91.2 ± 13.6 versus 81.4 ± 18.4, P = 0.003), and borderline differences in angina stability (61.2 ± 26.5 versus 51.0 ± 23.7, P = 0.046) compared to patients in the OMT group. There were no significant differences in SAQ scores in the OMT group at baseline and during the FUP. There was a statistically significant increase in all five domains in the PCI group.Symptoms and QoL measured by the SAQ were significantly improved after CTO PCI compared to OMT alone.

The Affinity of Some Lewis Bases for Hexafluoroisopropanol as a Reference Lewis Acid: An ITC/DFT Study.

To figure out the possible role of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) as well as to provide reference thermochemical data in solution, the formation of Lewis acid-base complexes between HFIP (Lewis acid) and a series of 8 different Lewis bases (3 sulfoxides, 3 Nsp2 pyridine derivatives, 1 aromatic amine, 1 cyclic aliphatic ether) was examined by isothermal titration calorimetry (ITC) experiments and static density functional theory augmented with Dispersion (DFT-D) calculations. Measured ITC association enthalpy values (ΔHa ) lie between -9.3 and -14 kcal mol-1 . Computations including a PCM implicit solvation model produced similar exothermicity of association of all studied systems compared to the ITC data with ΔHa values ranging from -8.5 to -12.7 kcal mol-1 . An additional set of calculations combining implicit and explicit solvation by chlorobenzene of the reactants, pointed out the relatively low interference of the solvent with the HFIP-base complexation: its main effect is to slightly enhance the Gibbs energy of the HFIP-Lewis base association. It is speculated that the interactions of bulk HFIP with Lewis bases therefore may significantly intervene in catalytic processes not only via the dynamic microstructuring of the medium but also more explicitly by affecting bonds' polarization at the Lewis bases.

How flexible is the water molecule structure? Analysis of crystal structures and the potential energy surface.

Water molecules from crystal structures archived in the CSD show a relatively large range both in the bond angle and bond lengths. High level ab initio calculations at the CCSD(T)/CBS level predicted a possibility for energetically low-cost (±1 kcal mol-1) changes of the bond angle and bond lengths in a wide range, from 96.4° to 112.8° and from 0.930 Å to 0.989 Å, respectively.

HPViewer: sensitive and specific genotyping of human papillomavirus in metagenomic DNA.

Motivation: Shotgun DNA sequencing provides sensitive detection of all 182 HPV types in tissue and body fluid. However, existing computational methods either produce false positives misidentifying HPV types due to shared sequences among HPV, human and prokaryotes, or produce false negative since they identify HPV by assembled contigs requiring large abundant of HPV reads. Results: We designed HPViewer with two custom HPV reference databases masking simple repeats and homology sequences respectively and one homology distance matrix to hybridize these two databases. It directly identified HPV from short DNA reads rather than assembled contigs. Using 100 100 simulated samples, we revealed that HPViewer was robust for samples containing either high or low number of HPV reads. Using 12 shotgun sequencing samples from respiratory papillomatosis, HPViewer was equal to VirusTAP, and Vipie and better than HPVDetector with the respect to specificity and was the most sensitive method in the detection of HPV types 6 and 11. We demonstrated that contigs-based approaches had disadvantages of detection of HPV. In 1573 sets of metagenomic data from 18 human body sites, HPViewer identified 104 types of HPV in a body-site associated pattern and 89 types of HPV co-occurring in one sample with other types of HPV. We demonstrated HPViewer was sensitive and specific for HPV detection in metagenomic data. Availability and implementation: HPViewer can be accessed at https://github.com/yuhanH/HPViewer/. Supplementary information: Supplementary data are available at Bioinformatics online.

Improved marginal adaptation of composite restorations by using different placement and light polymerization techniques.

PURPOSE: To verify the influence of placement and polymerization technique on the gap width between dentin and composite restoration. METHODS: Standardized cylindrical cavities (3 mm in diameter, 2 mm deep) with all margins in dentin were prepared on buccal and oral surfaces of 30 extracted human third molars. With regard to the different resin composite filling techniques used, the samples were randomly divided into three groups (n=20): bulk; incremental; pin. Each group was further subdivided into subgroups based on different light polymerization techniques): continuous (40 seconds); discontinuous (2 seconds of activation, followed by 10 seconds of dark interval, then light polymerization continued for 38 seconds). After finishing procedures, impressions were made using polyvinylsiloxane, and epoxy resin replicas were obtained and prepared for scanning electron microscopy. The percentage of the marginal gaps in relation to the whole margin was recorded and statistically analyzed (P)≤ 0.05). RESULTS: Marginal adaptation of composite restorations placed into the dentin cavities using pin and discontinuously light polymerized presented significantly better results than other two tested groups polymerized in the same manner. CLINICAL SIGNIFICANCE: The proposed modified incremental placement technique with a transparent glass pin reduces marginal leakage at the interface between composite restoration and dentin; leakage which can jeopardize the longevity of the restoration.