Rare case of a rudimentary medial metatarsal non-ossified structure

A 9-year-old boy presented with a rudimentary medial metatarsal non-ossified structure. We considered his condition to be classified as hypoplastic medial member type in the metatarsal type of medial ray polydactyly. When it was considered as polydactyly, it had the longest delay of ossification among reported cases.     

Differences in vertebral,tibial, and iliac cancellous bone metabolism in ovariectomized rats

Bone histomorphometry is usually performed on the iliac bone in humans and the tibia or vertebrae in rats. Bone metabolism differences among skeletal sites may be problematic when translating experimental results from rats to humans, but data on such differences in rats are lacking. Therefore, we examined the differences in bone structure and metabolism among skeletal sites using the lumbar vertebra (LV), tibia, and iliac bone obtained from ovariectomized or sham-operated rats preoperatively and at various times from 3 days to 26 weeks postoperatively. The trabeculae were thicker in the LV, where bone metabolism was less active than at other sites, and numerous fine trabeculae were observed in the tibia, where bone metabolism was more active. The iliac bone structure and metabolism were intermediate between those of the tibia and LV. Ovariectomy induced lower bone volume and higher bone metabolism in all skeletal sites, but the changes were greatest and occurred earliest in the tibia, followed by the iliac bone and then LV. Ovariectomy caused changes in bone metabolic markers, which occurred earlier than those in bone tissue. Activation frequency (Ac.f) increased after ovariectomy. At week 26 in ovariectomized rats, Ac.f was highest in the tibia (3.13 N/year) but similar between iliac bone (0.87 N/year) and LV (1.39 N/year). Ac.f is reportedly 0.3–0.4 N/year in the iliac bone of postmenopausal women, suggesting that bone turnover in rats is several times higher than in humans. The reference values reported here are useful for translating experimental results from rats to humans.     

Combination Metabolomics Approach for Identifying Endogenous Substrates of Carnitine/Organic Cation Transporter OCTN1

Purpose

Solute carrier SLC22A4 encodes the carnitine/organic cation transporter OCTN1 and is associated with inflammatory bowel disease, although little is known about how this gene is linked to pathogenesis. The aim of the present study was to identify endogenous substrates that are associated with gastrointestinal inflammation.

Methods

HEK293/OCTN1 and mock cells were incubated with colon extracts isolated from dextran sodium sulfate-induced colitis mice; the subsequent cell lysates were mixed with the amino group selective reagent 3-aminopyridyl-N-hydroxysuccinimidyl carbamate (APDS), to selectively label OCTN1 substrates. Precursor ion scanning against the fragment ion of APDS was then used to identify candidate OCTN1 substrates.

Results

Over 10,000 peaks were detected by precursor ion scanning; m/z 342 had a higher signal in HEK293/OCTN1 compared to mock cells. This peak was detected as a divalent ion that contained four APDS-derived fragments and was identified as spermine. Spermine concentration in peripheral blood mononuclear cells from octn1 gene knockout mice (octn1^?/?) was significantly lower than in wild-type mice. Lipopolysaccharide-induced gene expression of inflammatory cytokines in peritoneal macrophages from octn1^?/? mice was lower than in wild-type mice.

Conclusions

The combination metabolomics approach can provide a novel tool to identify endogenous substrates of OCTN1.

     

Synthesis,biological evaluation and in silico molecular docking of novel 1-hydroxy-naphthyl substituted heterocycles

The versatile precursor 2-acetyl-4-allyl-1-hydroxy naphthalene was synthesized efficiently via Claisen rearrangement 2-acetyl-1-allyloxynaphthalene. The Claisen-Schmidt condensation of latter precursor afforded the corresponding chalcones which were exploited to synthesize a series of potential heterocycles such as pyrazoline, isoxazoline, benzocoumarin and benzoflavone. The synthesized products showed potent antioxidant and antimicrobial activities. Chalcone 3c, naphthyl pyrazoline 6b and hydroxycoumarin 13 exhibited the highest activity as antioxidants. Their binding mode showed specialized recognition of hydroxycoumarin 13 with the triad key amino acids at the active site of the oxidoreductase enzyme (PDB code 1DXO). 1-Hydroxynaphth-2-yl pyrazoline (6b) revealed the highest efficacy against both Gram positive and negative bacterial species. In silico molecular docking of pyrazoline 6b endorsed its proper binding at the active site of the 2EX6 enzyme which explains its potent antibacterial activity in comparison with standard ampicillin.     

Immune Evasion of Hepatoma Cancer Stem-Like Cells from Natural Killer Cells

Annals of Surgical Oncology - Poor prognosis in liver cancer is due to its high frequency of intrahepatic metastasis. Cancer stem-like cells (CSLCs), which possess the properties of stemness, tumor...     

Alterations of 3D acetabular and lower limb parameters in adolescent idiopathic scoliosis

European Spine Journal - To evaluate the 3D deformity of the acetabula and lower limbs in subjects with adolescent idiopathic scoliosis (AIS) and their relationship with spino-pelvic alignment. Two...     

Chemoradiotherapy followed by restorative proctocolectomy with partial intersphincteric resection for advanced rectal cancer associated with ulcerative colitis: report of a case

The role of restorative proctocolectomy with ileal J-pouch anal anastomosis (IPAA) is uncertain for patients with ulcerative colitis (UC), when advanced lower rectal cancer is diagnosed. We report what to our knowledge is the first documented case of successful preoperative chemoradiotherapy followed by IPAA with partial intersphincteric resection of advanced rectal cancer associated with UC. A 59-year-old woman with a 24-year history of extensive UC was found to have advanced rectal cancer located 2 cm from the anal verge. She underwent preoperative conventional chemoradiotherapy followed by restorative proctocolectomy with total mesorectal excision. The procedure included intersphincteric resection of one quadrant and construction of an IPAA with diverting ileostomy. The postoperative course was uneventful, and the ileostomy was closed 6 months after the initial surgery. The patient was doing well with good pouch function and no evidence of recurrent disease 1 year after her initial surgery.     

Onset of fulminant type 1 diabetes mellitus following hypophysitis after discontinuation of combined immunotherapy. A case report

Diabetes is a rare, but potentially life-threatening, adverse event of immune checkpoint inhibitors that requires prompt recognition and treatment. It usually occurs in the first 3 months of treatment and is typically related to programmed cell death-1 antibodies, alone or in combined therapy. It has rarely been described developing after immunotherapy cessation. We present a 51-year-old man with metastatic melanoma, who developed acute-onset diabetes 52 days after combined immunotherapy cessation with nivolumab and ipilimumab, and 25.6 months after receiving the first dose. He presented with acute hyperglycemic symptoms, ketosis, complete insulin depletion and negative autoimmunity, fulfilling the criteria of fulminant type 1 diabetes. The patient had previously developed hypophysitis with isolated adrenocorticotropic hormone deficiency during immunotherapy. We describe a case of late-onset fulminant type 1 diabetes developing after immunotherapy cessation. Patient education and active follow up after immunotherapy discontinuation are crucial to warrant a timely intervention.