Apexification strategies in traumatised non-vital immature permanent teeth can promote root-end closure and continued root development. However, traumatic injuries may compromise the integrity of generative cells of the apical papilla responsible for root maturation. This report describes the long-term treatment outcome of mineral trioxide aggregate (MTA) apexification managed with late-term surgical intervention. A seven-year-old male reported with swelling and suppuration associated with a traumatised maxillary left central incisor (#21). After palliative treatment and MTA apexification procedures, the incisor demonstrated normal function during a 14.5-year period with radiographic evidence of atypical radicular elongation. Seventeen years after initial treatment, the patient presented with mid-plate buccal swelling and surgical treatment was completed involving root resection, biopsy of a spherical mineralised tissue specimen and placement of MTA root-end filling. Periapical healing and normal tooth function was evident at the 20-year review.

The aim of this study was to clarify the morphologic and morphometric characteristics of the adductor minimus (AMi) and to observe its topographic relationships relative to the adjacent anatomical structures.

This study investigated 54 thighs of 27 Korean cadavers.

The AMi was a small and flat muscle observed in 94.4% of the specimens. It originated from the inferior ramus of the pubis as the upper part of the adductor magnus (AMa), and inserted from the lesser trochanter to the upper part of the linea aspera. The AMi was completely separate from the AMa in 63.0% of the specimens. The medial circumflex femoral artery was always found at the superior border of the AMi, while the first and second perforating arteries were found inferior to the muscle in 55.6% and 37.0% of specimens, respectively. A supernumerary muscle (SM) was found with the AMi in 42.6% of the specimens, and it originated from the inferior ramus of the pubis and inserted into the posterior side of the lesser trochanter. The obturator externus and AMi were found superoposterior and inferior to the SM, respectively, while the posterior branch of the obturator nerve passed underneath it.

The results of this study may provide physicians with the accurate anatomical knowledge that they require for managing groin pain and applying a regional nerve block with ultrasound guidance in this adductor region.

The results of this study may provide physicians with the accurate anatomical knowledge that they require for managing groin pain and applying a regional nerve block with ultrasound guidance in this adductor region.Many cells are small and rounded on soft extracellular matrices (ECM), elongated on stiffer ECMs, and flattened on hard ECMs. Cells also migrate up stiffness gradients (durotaxis). Using a hybrid cellular Potts and finite-element model extended with ODE-based models of focal adhesion (FA) turnover, we show that the full range of cell shape and durotaxis can be explained in unison from dynamics of FAs, in contrast to previous mathematical models. In our 2D cell-shape model, FAs grow due to cell traction forces. Forces develop faster on stiff ECMs, causing FAs to stabilize and, consequently, cells to spread on stiff ECMs. If ECM stress further stabilizes FAs, cells elongate on substrates of intermediate stiffness. We show that durotaxis follows from the same set of assumptions. Our model contributes to the understanding of the basic responses of cells to ECM stiffness, paving the way for future modeling of more complex cell-ECM interactions.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i), or gliflozins, are anti-diabetic drugs that lower glycemia by promoting glucosuria, but they also stimulate endogenous glucose and ketone body production. The likely causes of these metabolic responses are increased blood glucagon levels, and decreased blood insulin levels, but the mechanisms involved are hotly debated. This study verified whether or not SGLT2i affect glucagon and insulin secretion by a direct action on islet cells in three species, using multiple approaches.

We tested the in vivo effects of two selective SGLT2i (dapagliflozin, empagliflozin) and a SGLT1/2i (sotagliflozin) on various biological parameters (glucosuria, glycemia, glucagonemia, insulinemia) in mice. mRNA expression of SGLT2 and other glucose transporters was assessed in rat, mouse, and human FACS-purified α- and β-cells, and by analysis of two human islet cell transcriptomic datasets. Immunodetection of SGLT2 in pancreatic tissues was performed with a validated antidirect action of the gliflozins on islet cells.

The data indicate that the SGLT2i-induced increase of the plasma glucagon/insulin ratio in vivo does not result from a direct action of the gliflozins on islet cells.Epigenetic modifications allow cells to quickly alter their gene expression and adapt to different stresses. In addition to direct chromatin modifications, prion-like proteins have recently emerged as a system that can sense and adapt the cellular response to stressful conditions. Interestingly, such responses are maintained through prions’ self-templating conformations and transmitted to the progeny of the cell that established a prion trait. Alternatively, mnemons are prion-like proteins which conformational switch encodes memories of past events and yet does not propagate to daughter cells. In this review, we explore the biology of the recently described prions found in Saccharomyces cerevisiae including [ESI+], [SMAUG+], [GAR+], [MOT3+], [MOD+], [LSB+] as well as the Whi3 mnemon. The reversibility of the phenotypes they encode allows cells to remove traits which are no longer adaptive under stress relief and chaperones play a fundamental role in all steps of prion-like proteins functions. Thus, the interplay between chaperones and prion-like proteins provides a framework to establish responses to challenging environments.Systemic lupus erythematosus (SLE) patients are at risk for pneumococcal infection. Twenty-one consecutive SLE patients (40[25-75] years) received the sequential PCV13/PPSV23 vaccine and factors associated with long-term protection were analyzed. Immune protection, defined by an antigen-specific IgG concentration ≥1.3 µg/mL for at least 70% of 7 pneumococcal serotypes was assessed at baseline, 2, 6, 12 and 36 months defining long-term protection. Only 10 patients showed pneumococcal immune protection 36 months after vaccination. Eleven (52.4%) patients had no long-term protection with a seroconversion that never or only transiently occurred. SLE disease features, treatment received and immunological characteristics did not differ between protected and unprotected patients except for the pre-vaccination IgG2 serum levels. Serum IgG2 level >2.125 µg/ml showed a sensitivity of 100% and a specificity of 90.9% for long-term protection. Sequential pneumococcal vaccination conferred poor immune protection in SLE. Baseline IgG2 serum level identified patients able to benefit from pneumococcal vaccination.

Children with laryngomalacia may present with obstructive sleep apnea (OSA). The role of polysomnography (PSG) in treatment decision making for laryngomalacia is not well defined. We aimed to investigate the prevalence of OSA in children with laryngomalacia and the role of PSG in treatment decision.

Retrospective medical record review of children with laryngomalacia, confirmed by direct laryngoscopy, during a period of 3 years. Demographic data, presenting symptoms, severity classification, comorbidities and pre- and postoperative PSG data were retrieved and analyzed. Data are expressed as a median (25th – 75th percentile).

Forty-six patients were with diagnosed laryngomalacia between March 2016 and April 2019. A complete data set was available for 44 patients, 24 males and 20 females. The median age at the time of PSG was 12 weeks (6.3-29.8). Thirty-four children (77.4%) were diagnosed with concomitant OSA. A diagnosis of OSA changed the severity classification and treatment decision in 24 cases (54.5% active intervention with CPAP therapy or supraglottoplasty. Supraglottoplasty is a safe and effective surgical procedure for laryngomalacia. When performed in the setting of laryngomalacia with concomitant OSA, it also significantly improves OSA symptomatology.

To determine the real-life efficacy, safety, and drug-retention rates of leflunomide (LEF) or methotrexate (MTX) as a synthetic DMARD used in combination with biological DMARDs for rheumatoid arthritis (RA).

The TReasure database is a web-based, prospective, observational cohort of RA and spondyloarthritis patients from 17 centres in different regions of Turkey and data entry was enabled since December 2017. Until May 2019, 2556 RA patients on biologic treatment were recorded. Demographic and RA-related data of 1526 patient either received LEF or MTX were compared, efficacy of both drugs compared by RA-disease activity composite indices. Reasons fordrug discontinuation also recorded. Drug retention rates were compared with Kaplan-Meier curves (log-rank test).

Of 2556 RA patients 1526 (59.7%) were receiving concomitant LEF (n=646, 42.3%; median follow up 35 months) or concomitant MTX (n=880, 57.3%; median follow-up 32 months) at the time of initiation to their first bDMARDs. The LEF group were older and had longer disease duration, proportion of females and seropositive patients was higher in this group. In the LEF group, non-anti-TNF agents were used in higher rate. Remission rates, changes in composite indices and rate of comorbidities and adverse events were similar in both groups. The retention rate of LEF + non-anti-TNF b/tsDMARDs was higher compared to MTX + anti-TNF bDMARDs (p=0.002, log-rank). Rates of adverse events were similar in both groups.

LEF in combination with either anti-TNF or non-anti-TNF drugs appears as an effective and safe therapeutic option at least as MTX.

LEF in combination with either anti-TNF or non-anti-TNF drugs appears as an effective and safe therapeutic option at least as MTX.

Decompressive craniectomy remains controversial because of uncertainty regarding its benefit to patients; this study aimed to explore current practice following the RESCUEicp Trial, an important study in the evolving literature on decompressive craniectomies.

Neurosurgeons in New Zealand, Australia, USA and Nepal were sent a survey consisting of two case scenarios and several multi-choice questions exploring their utilisation of decompressive craniectomy following the RESCUEicp Trial.

One in ten neurosurgeons (n

=

6, 10.3%) were no longer performing decompressive craniectomies for TBI following the RESCUEicp Trial and two fifths (n

=

23, 39.7%) were less enthusiastic. Most neurosurgeons would not operate in the face of severe disability (n

=

46, 79.3%) or vegetative state/death (n

=

57, 98.3%). Neurosurgeons tended give more optimistic prognoses than the CRASH prognostic model. Those who suggested more pessimistic prognoses and those who use decision support tools were less likely to advise decobe considered.

CLOCK and PER2 genes have been implicated in sleep-wake cycle alterations and neurodegenerative diseases. Our aim was to evaluate the effect of CLOCK T3111C and PER2 C111G on cognitive functioning in subjective cognitive decline (SCD) patients and mild cognitive impairment (MCI) patients at the baseline of a longitudinal study, and the effect of these two polymorphisms on the progression to Alzheimer’s disease (AD) of the two groups.

Sixty-eight subjects (41 SCD and 27 MCI) who underwent clinical evaluation, neuropsychological assessment, CLOCK and PER2 genotyping at baseline and neuropsychological follow-up every 2years for a mean time of 10years were included. Subjects who developed AD (SCD-c and MCI-c) and non-converters (SCD-nc, MCI-nc) were considered.

CLOCK T3111C was detected in 47% of cases (21 SCD, 11 MCI) and PER2 C111G in 19% of cases (eight SCD and five MCI). PER2 G carriers presented lower premorbid intelligence score (P=0.049), fewer years of education (P=0.007) and a lower frequency of family history of AD (P=0.