Plant transcripts with long or structured upstream open reading frames in the NDL2 5' UTR can escape nonsense-mediated mRNA decay in a reinitiation-independent manner.

Many eukaryotic transcripts contain upstream open reading frames (uORFs). Translated uORFs can inhibit the translation of main ORFs by imposing the need for reinitiation of translation. Translated uORFs can also lead to transcript degradation by the nonsense-mediated mRNA decay (NMD) pathway. In mammalian cells, translated uORFs were shown to target their transcripts to NMD if the uORFs were long (>23-32 amino acids), structured, or inhibit reinitiation. Reinitiation was shown to rescue uORF-containing mammalian transcripts from NMD. Much less is known about the significance of the length, structure, and reinitiation efficiency of translated uORFs for NMD targeting in plants. Although high-throughput studies suggested that uORFs do not globally reduce plant transcript abundance, it was not clear whether this was due to NMD-escape-permitting parameters of uORF recognition, length, structure, or reinitiation efficiency. We expressed in Arabidopsis reporter genes that included NDL2 5' untranslated region and various uORFs with modulation of the above parameters. We found that transcripts can escape NMD in plants even when they include efficiently translated uORFs up to 70 amino acids long, or structured uORFs, in the absence of reinitiation. These data highlight an apparent difference between the rules that govern the exposure of uORF-containing transcripts to NMD in mammalian and plant cells.

Weights, resistance bands, and rest days are best for tendinopathy.

The studyPavlova AV, Shim JSC, Moss R, et al. Effect of resistance exercise dose components for tendinopathy management: a systematic review with meta-analysis. Br J Sports Med 2023;57:1327-34.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/weights-resistance-bands-rest-days-best-tendinopathy/.

How common are side effects of treatment to prevent gout flares when starting allopurinol?

The studyRoddy E, Bajpai R, Forrester H, et al. Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink. Ann Rheum Dis 2023;82:1618-25.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/how-common-are-side-effects-of-treatment-to-prevent-gout-flares-when-starting-allopurinol/.

Irritable bowel syndrome: low dose antidepressant improves symptoms.

The studyFord AC, Wright-Hughes A, Alderson SL, et al. Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2023;402:1773-85.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/irritable-bowel-syndrome-low-dose-antidepressant-improves-symptoms/.

Surgery is better than nasal sprays for people with severely blocked airways caused by septal deviation.

The studyCarrie S, O'Hara J, Fouweather T, et al. Clinical effectiveness of septoplasty versus medical management for nasal airways obstruction: multicentre, open label, randomised controlled trial. BMJ 2023;383:e075445.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/surgery-is-better-than-nasal-sprays-for-people-with-severely-blocked-airways/.

Pelvic organ prolapse: self-management of pessaries can be a good option.

The studyHagen S, Kearney R, Goodman K, et al. Clinical effectiveness of vaginal pessary self-management vs clinic-based care for pelvic organ prolapse (TOPSY): a randomised controlled superiority trial. eClinicalMedicine 2023;66:102326.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/pelvic-organ-prolapse-self-management-of-pessaries-can-be-a-good-option/.

Even short periods of diabetes remission are linked to lower risk of heart attack and stroke.

The studyDambha-Miller H, Hounkpatin HO, Stuart B, Farmer A, Griffin S. Type 2 diabetes remission trajectories and variation in risk of diabetes complications: a population-based cohort study. PLoS ONE 2023;18. doi:10.1371/journal.pone.0290791To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/even-short-periods-of-diabetes-remission-are-linked-to-lower-risk-of-heart-attack-and-stroke/.

What are the chances of having a second epileptic seizure?

The studyNeligan A, Adan G, Nevitt SJ, et al. Prognosis of adults and children following a first unprovoked seizure. Cochrane Database Syst Rev 2023;1:1-75.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/epilepsy-what-are-the-chances-of-having-a-second-seizure/.

Weight regain does not eliminate the long term benefits of weight management programmes.

The studyHartmann-Boyce J, Theodoulou A, Oke JL, et al. Long term effect of weight regain following behavioral weight management programs on cardiometabolic disease incidence and risk: systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2023;16:263-76.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/weight-regain-does-not-eliminate-the-long-term-benefits-of-weight-management-programmes/#:~:text=Study%20author&text=Many%20people%20believe%20that%20if,been%20the%20case%20without%20it.

Combination therapy for painful diabetic neuropathy is safe and effective.

The studyTesfaye S, Sloan G, Petrie J, et al. Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial. Lancet 2022;400:680-90.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/combination-therapy-for-painful-diabetic-neuropathy-is-safe-and-effective/.

Online support improved eczema symptoms in children and young people.

The studySanter M, Muller I, Becque T. Eczema Care Online behavioural interventions to support self-care for children and young people: two independent, pragmatic, randomised controlled trials. BMJ 2022;379:e072007.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/online-support-improved-eczema-symptoms-in-children-and-young-people/.

One-session treatment is as effective as multi-session therapy for young people with phobias.

The studyWright B, Tindall L, Scott AJ, et al. One-session treatment compared with multisession CBT in children aged 7-16 years with specific phobias: the ASPECT non-inferiority RCT. Health Technol Assess 2022;26:1-174.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/one-session-cbt-treatment-effective-for-young-people-with-phobias/.

How to reduce medications for people with multiple long term conditions.

The studyReeve J, Maden M, Hill R, et al. Deprescribing medicines in older people living with multimorbidity and polypharmacy: the TAILOR evidence synthesis. Health Technol Assess 2022;26:1-148.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/how-to-safely-deprescribe-medications-for-people-with-multiple-long-term-conditions/.

Online cognitive behavioural therapy for post-traumatic stress disorder is as effective as face-to-face therapy.

The studyBisson JI, Ariti C, Cullen K, et al. Guided, internet based, cognitive behavioural therapy for post-traumatic stress disorder: pragmatic, multicentre, randomised controlled non-inferiority trial (RAPID). BMJ 2022;377:e069405.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/online-cbt-for-ptsd-is-as-effective-as-face-to-face-therapy/.

Routine follow-up may not be needed for people undergoing joint replacement surgery.

The studyKingsbury SR, Smith LK, Czoski Murray CJ, et al. Safety of disinvestment in mid- to late-term follow-up post primary hip and knee replacement: the UK SAFE evidence synthesis and recommendations. Health Soc Care Deliv Res 2022;10. doi:10.3310/KODQ0769To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/joint-replacement-many-people-can-safely-wait-10-years-for-follow-up/.

Early, intense therapy for language problems after a stroke is linked to the greatest benefits.

The studyBrady MC, Ali M, VandenBerg K, et al. Complex speech-language therapy interventions for stroke-related aphasia: the RELEASE study incorporating a systematic review and individual participant data network meta-analysis. Health Social Care Delivery Res 2022;10.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/therapy-for-language-problems-after-a-stroke-is-most-effective-when-given-early-and-intensively/.

Preventing cervical cancer: what are the risks and benefits of different treatments?

The studyKyrgiou M, Athanasiou A, Cieslak-Jones D. Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis. Lancet Oncol 2022;23:1097-108.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/prevention-of-cervical-cancer-what-are-the-risks-and-benefits-of-different-treatments/.

Assisted vaginal births: women who tear or have a surgical cut need prompt antibiotics.

The studyHumphries ABC, Linsell L, Knight M. Factors associated with infection after operative vaginal birth-a secondary analysis of a randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth. AJOG 2023;228:328.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/assisted-vaginal-births-women-need-prompt-antibiotics/.

One-stage hip revisions are as good as two-stage surgery to replace infected artificial hips.

The studyBlom AW, Lenguerrand, Strange S, et al. Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM): pragmatic, parallel group, open label, randomised controlled trial. BMJ 2022;379:e071281.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/one-stage-hip-revisions-are-as-good-as-2-stage-surgery-to-replace-infected-artificial-hips/.

Male sling is as good as more complex surgery for incontinence after prostate surgery.

The studyConstable L, Abrams P, Cooper D, et. Synthetic sling or artificial urinary sphincter for men with urodynamic stress incontinence after prostate surgery: the MASTER non-inferiority RCT. Health Technol Assess 2022;26:1-152To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/male-sling-is-as-good-as-more-complex-surgery-for-incontinence-after-prostate-surgery/.