Atypical Presentation of Gout: A Case Report.

Gout is the most common inflammatory arthritis which is caused by the buildup of uric acid crystals in the joints, that leads to severe pain, swelling, and stiffness. The condition typically affects the first metatarsophalangeal joint but it can impact other joints in the body. We present a case in which a 43-year-old male with a past medical history of obesity, hypertension, osteoarthritis, and gout presented with bilateral leg pain and the inability to walk for the last two years. Labs showed persistent leukocytosis, elevated ESR (erythrocyte sedimentation rate), normal uric acid levels, with physical exam findings of bilateral tender nodular leg lesions. Chest X-ray, head CT without contrast, left hip X-ray and ultrasound of left lower extremity were performed which were all negative. Biopsy of the tender skin nodules confirmed the diagnosis of tophaceous gout. Acute and prophylactic treatment of tophaceous gout resulted in resolved inflammation and leukocytosis without any complications.

Mixed Metal Allergy Ancillary to Surgical Staples.

Metal allergies to surgical clips are atypical and often neglected as a differential. It becomes even more unexpected when there is a lack of relevant medical history of the patient reacting poorly to known metals. This study entails the unique finding of newly discovered hypersensitivity to nickel and zirconium, metals commonly found in surgical clips, in a 28-year-old female who underwent laparoscopic cholecystectomy with a cholangiogram.

Upregulation of ß-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons (MNs). There are no effective treatments and patients usually die within 2-5 years of diagnosis. Emerging commonalities between familial and sporadic cases of this complex multifactorial disorder include disruption to RNA processing and cytoplasmic inclusion bodies containing TDP-43 and/or FUS protein aggregates. Both TDP-43 and FUS have been implicated in RNA processing functions, including microRNA biogenesis, transcription, and splicing. In this study, we explore the misexpression of microRNAs in an iPSC-based disease model of FUS ALS. We identify the downregulation of miR-139, an MN-enriched microRNA, in FUS and sporadic ALS MN. We discover that miR-139 downregulation leads to the activation of canonical WNT signaling and demonstrate that the WNT transcriptional mediator ß-catenin is a major driver of MN degeneration in ALS. Our results highlight the importance of homeostatic RNA networks in ALS.

Peanut-Related Perforated Diverticulitis Before the Age of 60.

We present a case in which a 55-year-old male with a past medical history of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) presented with sharp, worsening right-sided abdominal pain radiating across the entire abdomen after eating peanuts. Computed tomography (CT) imaging showed evidence of acute sigmoid diverticulitis complicated by a walled-off perforation. The patient's past medical history suggested previous recurrent episodes of diverticulitis. Our patient underwent exploratory laparotomy, sigmoid colon resection with low anterior anastomosis and proctocolectomy, and loop ileostomy. During treatment, the sigmoid colon was found to be very indurated and abnormally going all the way down to the peritoneal reflection. Appropriate identification of the patient's condition and timely intervention resulted in a successful outcome.

Persistent Small Bowel Obstruction due to Small Bowel Adenocarcinoma: A Case Report.

Small bowel obstruction (SBO), of both partial and complete types, is a condition predominantly caused by intra-abdominal adhesions and hernias. However, a known but very uncommon cause of SBO is malignancies, which are more complicated than those caused by adhesions and hernias, and associated with poorer prognoses; of these, small bowel adenocarcinoma is an even rarer etiology of SBO. The majority of SBO cases that are treated have resolution of symptoms and do not have recurrence/persistence of the condition; however, reports suggest that approximately one-fifth of SBO cases that are treated will result in recurrence/persistence of SBO requiring repeat admission. Here we report the case of an 89-year-old female with a past medical history of right lower extremity deep venous thrombosis, inferior vena cava filter placement, iron deficiency anemia, diverticular disease, internal hemorrhoids, sick sinus syndrome, emphysema, hypertension, dyslipidemia, and hypothyroidism, who presented with diarrhea and intermittent dark stool. Abdominal computed tomography (CT) while in the emergency department initially showed possible ischemic bowel and SBO. After an exploratory laparotomy with small bowel resection and adhesiolysis, pathological analysis of a resected specimen showed infiltrating small bowel adenocarcinoma. Persistence of symptoms necessitated subsequent abdominal imaging, which demonstrated persistent SBO, which was treated with a second exploratory laparotomy with small bowel resection and end ileostomy.

In vitro reconstitution of branching microtubule nucleation.

Eukaryotic cell division requires the mitotic spindle, a microtubule (MT)-based structure which accurately aligns and segregates duplicated chromosomes. The dynamics of spindle formation are determined primarily by correctly localising the MT nucleator, γ-Tubulin Ring Complex (γ-TuRC), within the cell. A conserved MT-associated protein complex, Augmin, recruits γ-TuRC to pre-existing spindle MTs, amplifying their number, in an essential cellular phenomenon termed 'branching' MT nucleation. Here, we purify endogenous, GFP-tagged Augmin and γ-TuRC from Drosophila embryos to near homogeneity using a novel one-step affinity technique. We demonstrate that, in vitro, while Augmin alone does not affect Tubulin polymerisation dynamics, it stimulates γ-TuRC-dependent MT nucleation in a cell cycle-dependent manner. We also assemble and visualise the MT-Augmin-γ-TuRC-MT junction using light microscopy. Our work therefore conclusively reconstitutes branching MT nucleation. It also provides a powerful synthetic approach with which to investigate the emergence of cellular phenomena, such as mitotic spindle formation, from component parts.

Drosophila Morgana is an Hsp90-interacting protein with a direct role in microtubule polymerisation.

Morgana (Mora, also known as CHORD in flies) and its mammalian homologue, called CHORDC1 or CHP1, is a highly conserved cysteine and histidine-rich domain (CHORD)-containing protein that has been proposed to function as an Hsp90 co-chaperone. Morgana deregulation promotes carcinogenesis in both mice and humans while, in Drosophila, loss of mora causes lethality and a complex mitotic phenotype that is rescued by a human morgana transgene. Here, we show that Drosophila Mora localises to mitotic spindles and co-purifies with the Hsp90-R2TP-TTT supercomplex and with additional well-known Hsp90 co-chaperones. Acute inhibition of Mora function in the early embryo results in a dramatic reduction in centrosomal microtubule stability, leading to small spindles nucleated from mitotic chromatin. Purified Mora binds to microtubules directly and promotes microtubule polymerisation in vitro, suggesting that Mora directly regulates spindle dynamics independently of its Hsp90 co-chaperone role.

Cleavable Affinity Purification (Cl-AP): A One-step Procedure to Affinity Purify Protein Complexes.

Cleavable Affinity Purification (Cl-AP) uses a tripartite system of Protein-A-Streptavidin beads and nanobodies, coupled with a biotinylated, thiol-cleavable linker, providing one-step affinity purification from lysates of tissues expressing tagged proteins. This technique allows fluorescent versions of mitotic protein complexes to be isolated intact from cells, for use in biophysical and microscopy-based assays, overcoming the traditional limitations of reductionist approaches. We have used this technique successfully to purify both GFP-tagged and mCherry-tagged proteins, and their interacting partners, expressed in Drosophila melanogaster embryos. Although we demonstrate the efficacy of the GFP-binding protein and RFP-binding protein nanobodies from Chromotek, in theory any antibody could be coupled to the beads and used as a Cl-AP reagent.