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RNA-catalyzed RNA ligation is widely believed to be a key reaction for primordial biology. However, since typical chemical routes towards activating RNA substrates are incompatible with ribozyme catalysis, it remains unclear how prebiotic systems generated and sustained pools of activated building blocks needed to form increasingly larger and complex RNA. Herein, we demonstrate in situ activation of RNA substrates under reaction conditions amenable to catalysis by the hairpin ribozyme. We found that diamidophosphate (DAP) and imidazole drive the formation of 2′,3′-cyclic phosphate RNA mono- and oligonucleotides from monophosphorylated precursors in frozen water-ice. This long-lived activation enables iterative enzymatic assembly of long RNAs. Our results provide a plausible scenario for the generation of higher-energy substrates required to fuel ribozyme-catalyzed RNA synthesis in the absence of a highly evolved metabolism.

To determine the health problems of LGBT individuals and the conditions of their utilization of health care services from their own perspectives.

Although the health care services have improved over the last decades, LGBT individual still face unique challenges when seeking health care services.

This study was performed using the phenomenological technique as a qualitative research method. The sample consisted of 18 LGBT individuals selected using purposive sampling. Data were collected by semi-structured interviews using focus group and analysed using content analysis.

Two main themes emerged as a result of the content analysis awareness and status of benefiting from health care.

To obtain quality care for LGBT individuals, the health care professionals need a persistent awareness-specific knowledge of LGBT health issues.

The findings of this study can be a warning for managers and policymakers to plan seriously to reform health care services infrastructures. Content about the health needs of LGBT individuals can be added to the curriculum of medical and nursing schools.

The findings of this study can be a warning for managers and policymakers to plan seriously to reform health care services infrastructures. Content about the health needs of LGBT individuals can be added to the curriculum of medical and nursing schools.

To evaluate the safety and efficacy of ketamine-magnesium combination to reduce attacks in a series of patients with refractory chronic cluster headache (rCCH).

Refractory chronic cluster headache (CCH) is a rare but highly debilitating condition that needs new treatment options. A previous publication reported that a single infusion of ketamine-magnesium combination was effective in 2 patients with rCCH.

The treatment was proposed to consecutive patients with rCCH seen in 2 French hospitals between November 2015 and February 2020 and who were resistant to at least 3 preventive treatments. They received a single ketamine infusion (0.5mg/kg over 2hours) combined with magnesium sulfate (3000mg). The main outcome was a comparison of the number of daily attacks 2weeks prior to the ketamine-magnesium infusion and 1week after (on days 7 and 8). The second outcome was the percentage of responders (patients with ≥50% reduction in the frequency of daily attacks). Safety was assessed by the recording of adverse events during infusion. Descriptive statistics are presented as mean±standard deviation.

Seventeen patients (14 men), with an age of 35.2±8.1years, were included. They presented with CCH for 6.6±4.3years. The number of daily attacks decreased from 4.3±2.4 before treatment to 1.3±1.0 after treatment (difference -3.1 (95% CI -4.5 to -1.6), P<.001). Seventy six percent (13/17) were responders. Transient and mild sedation was reported by 7/17 patients (41.2%).

The ketamine-magnesium combination seems an effective and well-tolerated therapy for rCCH. Placebo-controlled studies should be conducted to further confirm these findings.

The ketamine-magnesium combination seems an effective and well-tolerated therapy for rCCH. Placebo-controlled studies should be conducted to further confirm these findings.Clinicians often face dilemmas regarding the most appropriate way to restore a tooth following root canal treatment. Whilst there is established consensus on the importance of the ferrule effect on the predictable restoration of root filled teeth, other factors, such as residual tooth volume, tooth location, number of proximal contacts, timing of the definitive restoration and the presence of cracks, have been reported to influence restoration and tooth survival. The continued evolution of dental materials and techniques, combined with a trend towards more conservative endodontic-restorative procedures, prompts re-evaluation of the scientific literature. The aim of this literature review was to provide an updated overview of the existing clinical literature relating to the restoration of root filled teeth. PFI-2 clinical trial An electronic literature search of the PubMed, Ovid (via EMBASE) and MEDLINE (via EMBASE) databases up to July 2020 was performed to identify articles that related the survival of root filled teeth and/or restoration type. The following and other terms were searched restoration, crown, onlay, root canal, root filled, post, clinical, survival, success. Wherever possible, only clinical studies were selected for the literature review. Full texts of the identified articles were independently screened by two reviewers according to pre-defined criteria. This review identifies the main clinical factors influencing the survival of teeth and restorations following root canal treatment in vivo and discusses the data related to specific restoration type on clinical survival.Adaptive optics is being applied widely to a range of microscopies in order to improve imaging quality in the presence of specimen-induced aberrations. We present here the first implementation of wavefront-sensorless adaptive optics for a laser-free, aperture correlation, spinning disk microscope. This widefield method provides confocal-like optical sectioning through use of a patterned disk in the illumination and detection paths. Like other high-resolution microscopes, its operation is compromised by aberrations due to refractive index mismatch and variations within the specimen. Correction of such aberrations shows improved signal level, contrast and resolution.