Functional screening reveals HORMAD1-driven gene dependencies associated with translesion synthesis and replication stress tolerance.

HORMAD1 expression is usually restricted to germline cells, but it becomes mis-expressed in epithelial cells in ~60% of triple-negative breast cancers (TNBCs), where it is associated with elevated genomic instability (1). HORMAD1 expression in TNBC is bimodal with HORMAD1-positive TNBC representing a biologically distinct disease group. Identification of HORMAD1-driven genetic dependencies may uncover novel therapies for this disease group.

The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin.

Poly (ADP-ribose) polymerase (PARP) inhibitors elicit antitumour activity in homologous recombination-defective cancers by trapping PARP1 in a chromatin-bound state. How cells process trapped PARP1 remains unclear. Using wild-type and a trapping-deficient PARP1 mutant combined with rapid immunoprecipitation mass spectrometry of endogenous proteins and Apex2 proximity labelling, we delineated mass spectrometry-based interactomes of trapped and non-trapped PARP1.

Sirtuin inhibition is synthetic lethal with BRCA1 or BRCA2 deficiency.

PARP enzymes utilise NAD as a co-substrate for their enzymatic activity. Inhibition of PARP1 is synthetic lethal with defects in either BRCA1 or BRCA2. In order to assess whether other genes implicated in NAD metabolism were synthetic lethal with BRCA1 or BRCA2 gene defects, we carried out a genetic screen, which identified a synthetic lethality between BRCA1 and genetic inhibition of either of two sirtuin (SIRT) enzymes, SIRT1 or SIRT6.

Snapping Hamstring Tendons Case Report: Tenotomy and Tendon Transposition.

Case: A 14-year-old girl with a hypermobility syndrome presented with bilateral snapping semimembranosus (SM) and semitendinosus (ST) tendons. After failure of conservative treatment, she was treated with tenotomy of SM and later tendon transposition of her ST to her gracilis.

Conclusions: Surgical treatment of snapping hamstring tendons has historically consisted of the release of the tendon insertions (tenotomy) or tendon harvest.

Do Relaxation Exercises Decrease Pain After Arthroscopic Rotator Cuff Repair? A Randomized Controlled Trial.

Background: Pain after rotator cuff repair is commonly managed with opioid medications; however, these medications are associated with serious adverse effects. Relaxation exercises represent a potential nonpharmacologic method of pain management that can be easily implemented without substantial adverse effects; however, the effects of relaxation exercises have not been studied in a practical, reproducible protocol after arthroscopic rotator cuff repair.

Questions/purposes: (1) Does performing relaxation exercises after arthroscopic rotator cuff repair (ARCR) decrease pain compared with standard pain management medication? (2) Does performing relaxation exercises after ARCR decrease opioid consumption? (3) What proportion of patients who used the relaxation techniques believed they decreased their pain level, and what proportion continued using these techniques at 2 weeks? (4) Does performing relaxation exercises after ARCR affect shoulder function?

Methods: During the study period, 563 patients were eligible for inclusion; however, only 146 were enrolled, randomized, and postoperatively followed (relaxation group: 74, control group: 72); 68% (384 of 563) of patients were not contacted due to patient and research staff availability.