Nelsonstein5052
Mutations in the BRCA1 gene cause an extremely high lifetime risk of breast and ovarian cancer, but the exact mechanism by which the BRCA1 protein acts to prevent cancer onset remains unclear. In this edition of Cancer Research, Park and colleagues describe a new mouse model featuring a single amino acid substitution in the coiled-coil motif of BRCA1. This change prevents BRCA1 from interacting with PALB2 (partner and localizer of BRCA2), causing rapid cancer onset and a loss of blood cells similar to Fanconi anemia.See related article by Park et al., p. 4172.Significant advances in tumor sequencing have led to an explosion in our knowledge of the genetic complexity of cancer. learn more For many cancers, the selection of a targetable alteration is not readily apparent, especially when confronted with mutational variants of unknown significance. The complex clinical landscape of MEK mutations illustrates the need for improved methods to identify those patients, independent of tumor histology, who would benefit from treatment with a MAP kinase pathway inhibitor. In this issue of Cancer Research, Hanrahan and colleagues adopt an in silico platform to attempt to distinguish benign MEK mutations from those that are functional and, therefore, most likely to be therapeutically actionable.See related article by Hanrahan et al., p. 4233.Early cancer diagnosis is critical for improving patient survival and mortality rates, but most diagnostics on solid tumors rely on imaging tests with limited sensitivity and specificity to identify potential cases, which are then confirmed by tissue biopsies. However, this process is usually not suitable for cancer screening or evaluation of tumor responses to treatment. Liquid biopsies have the potential to bridge this gap, but few such assays have been approved for cancer applications. Extracellular vesicles hold particular promise for liquid biopsy diagnostics but are currently limited by the lack of robust methods for isolation and analysis. New isolation and analysis techniques, however, show promise to improve the clinical utility of extracellular vesicle-based cancer diagnosis.Precision medicine has exploited next-generation sequencing (NGS) and gene/immune-targeted drug deployment to transform the outlook for several lethal cancers. For instance, there are now several FDA-approved medications that target the sequelae of aberrant genes in a tissue-agnostic approach pembrolizumab [microsatellite instability and tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb)] and larotrectinib/entrectinib (NTRK fusions). Molecular interrogation further reveals the disruptive reality that metastatic cancers are tremendously complex and individually distinct. Therefore, optimized treatment often requires drug combinations (rather than monotherapy) and N-of-one customization. Early studies of this approach suggest feasibility, safety, and efficacy. Real-world data/master registry trials may also provide massive, clinically relevant datasets that further fuel the (r)evolution in oncology.
Adhesive capsulitis of the hip is a rare presenting pathology. History and physical examination are essential for diagnosis. Conservative management is the main line of treatment with surgical intervention preserved for resistant cases.
The authors report a case of young female diagnosed with adhesive capsulitis of the hip with two pain free periods during pregnancy and after arthrogram.
The relation between the pregnancy hormones and generalized laxity is well established. Animals studies proved the role of female hormones in treatment of adhesive capsulitis of the shoulder.
Hip pain relief during pregnancy can raise the suspicion of adhesive capsulitis of the hip. Further investigations are needed to prove this relation.
Hip pain relief during pregnancy can raise the suspicion of adhesive capsulitis of the hip. Further investigations are needed to prove this relation.
Sleep apnoea-hypopnoea syndrome (SAHS) and childhood obesity are la high prevalence conditions that represent a public health challenge.
To analyse the association between both and comparing child groups that had or did not have both conditions.
A prospective study in children (3-14 years), referred to the "Multidisciplinary Sleep Unit" due to suspected SAHS, between 1 November 2015 and 1 August 2017. The following parameters were evaluated anthropometry, symptoms, blood pressure, ear, nose, and throat examination, polysomnography (nocturnal PSG) and laboratory tests.
A total of 67 children were evaluated (64% non-obese and 36% obese. It was observed that the obese were older (P<.001), slept less hours (P=.028), did less physical exercise (P=.029), ate less in the school dining room (P=.009), had la lower sleep efficiency, and had abnormal values in carbohydrate and lipid metabolism. The children with SAHS were younger (P=.010), a high percentage of daytime sleepiness (P=.001), and breathing througThe children diagnosed with SAHS were in the higher percentile of diastolic blood pressure. Obesity was associated with worse sleep quality, and changes in carbohydrate and lipid metabolism.
Juvenile recurrent chronic parotitis is a rare disease of unknown cause. There is a growing interest in its autoimmune aetiology and its relationship with dysfunctions of cellular and humoral immunity, although there is no agreed protocol for complementary investigations for its study. A consecutive series of cases is presented where the immune alterations and associated autoimmune disorders are investigated, proposing a study algorithm.
A retrospective study was carried out on patients who had juvenile recurrent chronic parotitis during the period from 2013 to 2016 and a follow-up of at least 2 years. After its clinical and ultrasound diagnosis, complementary examinations were systematically carried out to investigate infectious, immune, and autoimmune diseases.
Of a total of 36 patients with inclusion criteria, 16 (44%) were found with some analytical alteration of a non-specific immunological nature (positive ANA, high IgG, low complement factor 4), or associated with a specific diagnosis, as occurred in 11 patients Selective IgA deficiency (2), Sjögren's syndrome associated or not with systemic lupus erythematosus (3), coeliac disease associated or not with diabetes mellitus (4), Hashimoto's thyroiditis (1), and acquired immunodeficiency syndrome (1).
