Rapidly fatal SMARCA4-deficient undifferentiated sarcoma originating from hybrid hemosiderotic fibrolipomatous tumor/pleomorphic hyalinizing angiectatic tumor of the foot

Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts and hemosiderotic fibrolipomatous tumor (HFLT) are two rare low-grade locally recurring neoplasms with predilection for the foot/ankle. Recent studies support a close link between the two entities, and origin of PHAT from HFLT and occurrence of hybrid HFLT/PHAT have been documented. Both lesions often harbor TGFBR3 or MGEA5 rearrangements. Rare sarcomas originating from HFLT/PHAT have been reported, typically resembling myxofibrosarcoma or myxoinflammatory fibroblastic sarcoma. We describe a novel SMARCA4-deficient undifferentiated sarcoma with rhabdoid features originating from hybrid HFLT/PHAT in the foot of a 54-year-old male. The tumor pursued a highly aggressive course with rapid regrowth after resection and multiple metastases resulting in patient’s death within 5 months, despite systemic chemotherapy. Immunohistochemistry revealed SMARCA4 loss in the undifferentiated sarcoma, but not in the HFLT/PHAT. Molecular testing confirmed TGFBR3/MGEA5 rearrangements. This report expands the phenotypes of sarcomas developing from pre-existing PHAT/HFLT.

ROOT FORMATION STIMULATORS AND THEIR INFLUENCE ON THE ROOTING OF GREEN AND WOODEN CUTTINGS OF PEAR CLONE

In the garden of Omsk Agrarian Scientific Center, located in the southern forest-steppe of Omsk region in 2018-2020 research has been carried out with the aim of studying the features of the influence of various stimulants of root formation during the propagation of clonal pear rootstocks by green and lignified cuttings. The soil is meadow-chernozemic medium loamy with a pronounced sandy fraction, the reaction of the soil solution is close to neutral. The object of research is clonal pear stocks PG 2, PG 12, PG 17-16. Rooting of green and lignified cuttings was carried out in a greenhouse with a film coating with an artificial fogging installation. The substrate is a mixture of sand and peat (1 to 1). Planting scheme of cuttings 5×5 cm, in four replicates (50 pcs.), Placement is randomized. Kornevin (powdering of sections), and Ribav-extra, control – water (duration of exposure - 16 h) were used as stimulants of root formation during green cuttings. When propagating by lignified cuttings, cornevin (0,1%) and ribav-extra (0,01%) were used; water was used as control (exposure duration - 16 h). Clonal pear rootstocks tolerated the winter conditions of the study years relatively favorably. The exception was winter 2019-2020, the total degree of freezing was 1 point in the PG 2 and PG 17-16 rootstocks, and 5 points in the PG 12 rootstock (90% plant loss). The beginning of the growing season in 2018 was marked on May 22-23, in 2019 - May 5-6, in 2020 - April 18-19. In 2018-2019, green cuttings were carried out on June 20, in 2020 - on June 10. Earlier terms of cuttings in 2020 are explained by the rapid regrowth and lignification of the shoots (hot weather and lack of precipitation in the first months of the growing season). In the control, massive root formation was noted after 6 weeks. The treatment of cuttings with growth stimulants promoted the acceleration of root formation, which was observed after 4 ... 5 weeks. On average, over the years of research, rooting rate when using Kornevin, in comparison with control, increased by 13 ... 18%, Ribav -extra - by 10 ... 13%. The rootstock PG 12 is characterized by a higher rooting Kornevin of green cuttings (51.5 ... 56.5%) than that of PG 2 (47.7 ... 49%) and PG 17-16 (41.7 ... 44.3%). Rooting rate when using Kornevin was 50%, Ribav - extra 47%. PG 12 is the only rootstock under study in which rooting of lignified cuttings is observed: in the control 24%, when using preparations 44.5 ... 52%

Diagnosis and clinical outcome following surgical resection of an intracranial grade III anaplastic gemistocytic astrocytoma in a cat

Case summary A 10-year-old Maine Coon cat was presented for acute onset seizures and cerebrothalamic signs. An intracranial mass, suspected to be a meningioma, was diagnosed on MRI and surgically excised. Histopathology appeared consistent with an atypical meningioma. However, following rapid regrowth of the neoplasm, the patient was humanely euthanized 3 months later. On post-mortem histopathology, the neoplasm was diagnosed as a grade III anaplastic gemistocytic astrocytoma. Relevance and novel information Gemistocytic astrocytomas are rare brain tumors in the feline patient. This case represents the first report of a feline grade III anaplastic gemistocytic astrocytoma in the cerebrum of a cat with surgical excision and recurrence. The challenging nature of ante-mortem diagnosis and the guarded prognosis, despite surgical intervention, are presented in this report.

Transcriptome Analysis of Wounding in the Model Grass Lolium temulentum

For forage and turf grasses, wounding is a predominant stress that often results in extensive loss of vegetative tissues followed by rapid regrowth. Currently, little is known concerning the perception, signaling, or molecular responses associated with wound stress in forage- and turf-related grasses. A transcriptome analysis of Lolium temulentum plants subjected to severe wounding revealed 9413 upregulated and 7704 downregulated, distinct, differentially expressed genes (DEGs). Categories related to signaling, transcription, and response to stimuli were enriched in the upregulated DEGs. Specifically, sequences annotated as enzymes involved in hormone biosynthesis/action and cell wall modifications, mitogen-activated protein kinases, WRKY transcription factors, proteinase inhibitors, and pathogen defense-related DEGs were identified. Surprisingly, DEGs related to heat shock and chaperones were more prevalent in the downregulated DEGs when compared with the upregulated DEGs. This wound transcriptome analysis is the first step in identifying the molecular components and pathways used by grasses in response to wounding. The information gained from the analysis will provide a valuable molecular resource that will be used to develop approaches that can improve the recovery, regrowth, and long-term fitness of forage and turf grasses before/after cutting or grazing.

Meropenem-Tobramycin Combination Regimens Combat Carbapenem-Resistant Pseudomonas aeruginosa in the Hollow-Fiber Infection Model Simulating Augmented Renal Clearance in Critically Ill Patients

ABSTRACT Augmented renal clearance (ARC) is common in critically ill patients and is associated with subtherapeutic concentrations of renally eliminated antibiotics. We investigated the impact of ARC on bacterial killing and resistance amplification for meropenem and tobramycin regimens in monotherapy and combination. Two carbapenem-resistant Pseudomonas aeruginosa isolates were studied in static-concentration time-kill studies. One isolate was examined comprehensively in a 7-day hollow-fiber infection model (HFIM). Pharmacokinetic profiles representing substantial ARC (creatinine clearance of 250 ml/min) were generated in the HFIM for meropenem (1 g or 2 g administered every 8 h as 30-min infusion and 3 g/day or 6 g/day as continuous infusion [CI]) and tobramycin (7 mg/kg of body weight every 24 h as 30-min infusion) regimens. The time courses of total and less-susceptible bacterial populations and MICs were determined for the monotherapies and all four combination regimens. Mechanism-based mathematical modeling (MBM) was performed. In the HFIM, maximum bacterial killing with any meropenem monotherapy was ∼3 log10 CFU/ml at 7 h, followed by rapid regrowth with increases in resistant populations by 24 h (meropenem MIC of up to 128 mg/liter). Tobramycin monotherapy produced extensive initial killing (∼7 log10 at 4 h) with rapid regrowth by 24 h, including substantial increases in resistant populations (tobramycin MIC of 32 mg/liter). Combination regimens containing meropenem administered intermittently or as a 3-g/day CI suppressed regrowth for ∼1 to 3 days, with rapid regrowth of resistant bacteria. Only a 6-g/day CI of meropenem combined with tobramycin suppressed regrowth and resistance over 7 days. MBM described bacterial killing and regrowth for all regimens well. The mode of meropenem administration was critical for the combination to be maximally effective against carbapenem-resistant P. aeruginosa.

Contribution of mouse adrenal glands to intratumor androgens and growth of castration-resistant prostate cancer xenografts.

224 Background: Historical studies using radioimmunoassay did not detect adrenal androgens in serum from castrate mice, and it is widely held that rodent adrenal glands do not make adrenal androgens due to lack of CYP17A expression. This contrasts with the clinical setting in which circulating adrenal androgens are significant and inhibition of adrenal CYP17A markedly decreases tissue androgens. Methods: We evaluated CYP17A (by methylation, transcript and protein) and androgens (by mass spectrometry) in adrenal glands of CB17-NOD/SCID mice. We determined the impact of adrenalectomy (ADX) on suppressing tumor androgens and growth in two patient derived xenografts (PDX) models of castration resistant prostate cancer (CRPC). Results: CYP17A is unmethylated, and transcript and protein are present in adrenals from intact and castrate mice. In castrate mice adrenal levels of DHEA (0.75 pg/mg), androstenedione (AED; 44pg/mg), T (12.5pg/mg) and DHT (4.7 pg/mg) are detectable and nearly 2 orders of magnitude higher than in kidney, liver or muscle (p < 0.05 for all). In castrate mice bearing LuCaP35 and LuCaP96 tumors, ADX suppressed tumor steroids at 21-30 days after ADX vs castration alone (LuCaP35: AED 0.05 vs 0.02 pg/mg, p = 0.005; T 0.64 vs 0.03 pg/mg p < 0.001; DHT 2.3 vs 0.23 pg/mg, p = 0.0003; LuCaP96: AED 0.06 vs 0.02 pg/mg p = 0.08; T 0.81 vs 0.03 pg/mg, p < 0.0001; DHT 1.3 vs 0.04 pg/mg, p = 0.002), and delayed time to tumor re-growth (median survival: LuCaP35 33 vs 179 days, p = 0.006; LuCaP96 25 vs 301 days, p = 0.0012). Whereas tumor recurrence in LuCaP96 was uniformly delayed, a subset of tumors in LuCaP35 showed more rapid regrowth after ADX (66 days vs undefined, p = 0.008), with a trend toward increased levels of tumor steroids (progesterone 0.25 vs 0.02 pg/mg, p = 0.07; T 0.14 vs 0.02, p = 0.04; DHT 0.36 vs 0.21, p = 0.17). Recurrent tumors variably showed induction of full length and truncated AR variants and/or induction of steroidogenic enzymes as potential mechanisms of resistance. Conclusions: Adrenally-derived steroids are produced in mice and contribute to tumor androgen levels and growth in PDX models. Mice are an appropriate model for evaluation of steroidogenesis inhibitors in CRPC xenograft studies

Republished: Rapid delayed growth of ruptured supraclinoid blister aneurysm after successful flow diverting stent treatment

A 62-year-old woman presented with a subarachnoid hemorrhage secondary to a ruptured right supraclinoid internal carotid artery blister aneurysm. She was treated in an emergent fashion with two flow diverting pipeline embolization devices (PED) deployed in a telescoping fashion. CT angiography performed for unrelated reasons at 7 months showed successful treatment of the aneurysm without evidence of residual aneurysm. However, a follow-up digital subtraction angiogram performed at 9 months showed a large aneurysm in a modified position compared with the original aneurysm. This is the first case of rapid regrowth of a supraclinoid blister aneurysm after successful treatment with a PED, and demonstrates the need for close follow-up for similar aneurysms treated with this novel device.