Three-hit hypothesis in astrocytoma: tracing the polymorphism D1853N in ATM gene through a pedigree of the proband affected with primary brain tumor

Ataxia telangictasia mutated (ATM) is involved in DNA repair pathway and cell-cycle checkpoints. ATM alterations were found in medulloblastomas, gliomas, but not in astrocytoma. The polymorphism D1853N was reported in healthy individuals and medulloblastomas. We could observe this polymorphism, heterozygously, in a proband affected with astrocytoma and traced it through her pedigree. We propose the three-hit hypothesis as a triangle initiators includes D1853N as a first predisposing hit, IVS 38- 63T → A as a second hit deriving from the first somatic evolution before differentiation and IVS 38- 30 A → G as a third hit through the development of an astrocytoma. In addition, the D1853N polymorphism was occurred in different allele from IVS 38- 63T → A and IVS 38- 30 A → G.     

Effect of Rosmarinic Acid on Sertoli Cells Apoptosis and Serum Antioxidant Levels in Rats After Exposure to Electromagnetic Fields

Rosmarinic acid belongs to the group of polyphenols; it has antioxidant, anti-inflammatory and antimicrobial activities and help to prevent cell damage caused by free radicals. The objective was to study the effect of Rosmarinic acid on sertolli cells apoptosis and serum antioxidant levels in rats after they were exposed to electromagnetic fields. Male Wistar rats (n=40) were allocated into three groups: control group (n=10) that received 5cc normal saline (0.9% NaCl) daily by gavage method, Rosmarinic acid group that received 5mg/rat (gavage) (n=10), electromagnetic fields (EMF) group that had exposure with 50hz (n=20) which was subdivided to two groups of 10; EMF group and treatment group. Treatment group received 5mg/rat (gavage) Rosmarinic acid daily for 6weeks, respectively. However, the control group just received an equal volume of distilled water daily (gavage). On the 42nd day of research, 5cc blood was collected to measure testosterone hormones, total antioxidant capacity (TAC), levels from whole group''s analysis. Level of malondialdehyde (MDA) levels and sertoli cells apoptosis significantly decreased in the group that received 5mg/rat of Rosmarinic acid (P<0.05) in comparison with experimental groups. Level of testosterone, total antioxidant capacity (TAC), significantly increased in groups that received Rosmarinic acid (P<0.05). Since in our study 5mg/rat of Rosmarinic acid showed significantly preventive effect on cell damages especial sertoli cells apoptosis that caused with EMF, it seems that using Rosmarinic acid as food additive can be effective for supporting people living under EMF environmental pollution.     

The Effect of Quince Leaf (Cydonia Oblonga Miller) Decoction on Testes in Hypercholesterolemic Rabbits: A Pilot Study

Current medical literature lacks any evidence of the protective effects of quince leaf on testes. Therefore, the aim of the present study was to assess the effect of quince (Cydonia oblonga Miller) leaf decoction on testicular injury and impaired spermatogenesis induced by hypercholesterolemia in rabbits. Eleven mature New Zealand white male rabbits were randomly divided into three groups: group 1 (hypercholesterolemia, n=3), group 2 (hypercholesterolemia plus quince treatment, n=6), and group 3 (control, n=2). Groups 1 and 2 received a cholesterol-enriched diet for six weeks. Group 2 received C. oblonga leaf decoction as drinking supplement as well. After six weeks, a normal diet was substituted in groups 1 and 2 for another six weeks. Group 3 (control group) was maintained throughout the study on a regular diet. At the end of the 12^th week, the left testes of the animals were resected for light microscopic study with particular attention to the maturity of germ cells in seminiferous tubules using Johnsen''s score. Increase in intertubular connective tissue and diameter of vessels, abundant spermatogonia and primary spermatocytes along the reduced germinal epithelium were noted in all rabbits of the group 1. The remaining animals in groups 2 and 3 had no significant changes in their testicular sections. The mean Johnsen''s score of group 1 (4.20±1.92) was significantly lower than that of group 2 (7.33±0.52) and group 3 (7.05±0.07). (P=0.01). In conclusion, quince leaf decoction (C. oblonga Miller) protected rabbit testes and spermatogenesis from damage induced by hypercholesterolemia.     

FDA Approval Summary: Olaparib Monotherapy or in Combination with Bevacizumab for the Maintenance Treatment of Patients with Advanced Ovarian Cancer

On December 19, 2018, the U.S. Food and Drug Administration (FDA) granted approval to olaparib monotherapy for first‐line maintenance treatment of BRCA‐mutated (BRCAm) advanced ovarian cancer and, on May 8, 2020, expanded the indication of olaparib to include its use in combination with bevacizumab for first‐line maintenance treatment of homologous recombination deficient (HRD)–positive advanced ovarian cancer. Both these approvals were based on randomized, double‐blind, placebo‐controlled trials. Approval for olaparib monotherapy was based on the SOLO‐1 trial, comparing the efficacy of olaparib versus placebo in patients with BRCAm advanced ovarian, fallopian tube, or primary peritoneal cancer after surgical cytoreduction and first‐line platinum‐based chemotherapy. Two companion diagnostic (CDx) tests were approved with this indication: BRACAnalysis CDx, for germline BRCA1/2 alterations, and FoundationOne CDx, for BRCA1/2 alterations in tissue specimens. Approval for olaparib in combination with bevacizumab was based on the results of the PAOLA‐1 trial that compared olaparib with bevacizumab versus placebo plus bevacizumab in patients with advanced high‐grade epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer after first‐line platinum‐based chemotherapy and bevacizumab. Myriad myChoice CDx was designated as a companion diagnostic device for use of olaparib plus bevacizumab combination for ovarian cancer associated with HRD‐positive status. Both trials demonstrated clinically meaningful improvements in progression‐free survival and favorable benefit‐risk profiles for the indicated populations. This article summarizes the FDA thought process and data supporting the approval of olaparib as monotherapy and in combination with bevacizumab for maintenance therapy in this setting.Implications for PracticeThese approvals represent the first poly (ADP‐ribose) polymerase inhibitor, alone or in combination with bevacizumab, approved in first‐line maintenance treatment of women with advanced ovarian cancer after cytoreductive surgery and chemotherapy. In patients with BRCA‐mutated tumors, olaparib monotherapy demonstrated a 70% reduction in the risk of disease progression or death compared with placebo, and olaparib in combination with bevacizumab demonstrated a 67% reduction in the risk of disease progression or death compared with bevacizumab alone in homologous recombination deficient–positive tumors. These approvals represent a major advance for the treatment of women with advanced ovarian cancer who are in complete or partial response after their initial platinum‐based chemotherapy.     

Correlation of standardized testing results with success on the 2001 American Board of Physical Medicine and Rehabilitation Part 1 Board Certificate Examination

OBJECTIVE: To determine if standardized testing results and other factors correlate with success on the 2001 American Board of Physical Medicine and Rehabilitation part 1 board certification examination (POE). DESIGN: An anonymous two-part survey was distributed to 302 senior resident physicians in the American College of Graduate Medicine Education-accredited physical medicine and rehabilitation training programs in the United States deemed eligible for the 2001 POE. RESULTS: A total of 94 of 302 distributed surveys (31.1%) were returned; 86 met the inclusion criteria (81 passes and five failures). A significant correlation was found between both quartile ranking on the Self Assessment Examination and United States Medical Licensing Examination (USMLE) passage on the first attempt with POE quartile rank (P < 0.01). Other factors, such as number of hours of faculty-led didactics per week, textbook use, and participation in formal board review courses did not correlate with POE quartile ranking. CONCLUSION: Residents who were successful on previous standardized tests scored well on the POE. Quartile ranking on Self Assessment Examination and USMLE or National Board of Osteopathic Medical Examiners success was found to correlate significantly with POE quartile rank. This information may be helpful for future POE preparation and prospective candidate selection for physical medicine and rehabilitation.     

CXCR4–CXCL12 interaction is important for plasma cell homing and survival in NZB/W mice

Antibody‐secreting cells (ASCs), including short‐lived plasmablasts and long‐lived memory plasma cells (LLPCs), contribute to autoimmune pathology. ASCs, particularly LLPCs, refractory to conventional immunosuppressive drugs pose a major therapeutic challenge. Since stromal cells expressing C‐X‐C motif chemokine‐12 (CXCL12) organize survival niches for LLPCs in the bone marrow, we investigated the effects of CXCL12 and its ligand CXCR4 (C‐X‐C chemokine receptor 4) on ASCs in lupus mice (NZB/W). Fewer adoptively transferred splenic ASCs were retrieved from the bone marrow of recipient immunodeficient Rag1^?/? mice when the ASCs were pretreated with the CXCR4 blocker AMD3100. CXCR4 blockade also significantly reduced anti‐OVA ASCs in the bone marrow after secondary immunization with OVA. In this study, AMD3100 efficiently depleted ASCs, including LLPCs. After two weeks, it decreased the total number of ASCs in the spleen and bone marrow by more than 60%. Combination with the proteasome inhibitor bortezomib significantly enhanced the depletion effect of AMD3100. Continuous long‐term (five‐month) CXCR4 blockade with AMD3100 after effective short‐term LLPCs depletion kept the number of LLPCs in the bone marrow low, delayed proteinuria development and prolonged the survival of the mice. These findings identify the CXCR4‐CXCL12 axis as a potential therapeutic target likely due to its importance for ASC homing and survival.