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41.
Gianetti E Hall JE Au MG Kaiser UB Quinton R Stewart JA Metzger DL Pitteloud N Mericq V Merino PM Levitsky LL Izatt L Lang-Muritano M Fujimoto VY Dluhy RG Chase ML Crowley WF Plummer L Seminara SB 《The Journal of clinical endocrinology and metabolism》2012,97(9):E1798-E1807
Context: A broad spectrum of GnRH-deficient phenotypes has been identified in individuals with both mono- and biallelic GNRHR mutations. Objective: The objective of the study was to determine the correlation between the severity of the reproductive phenotype(s) and the number and functional severity of rare sequence variants in GNRHR. Subjects: Eight hundred sixty-three probands with different forms of GnRH deficiency, 46 family members and 422 controls were screened for GNRHR mutations. The 70 subjects (32 patients and 38 family members) harboring mutations were divided into four groups (G1-G4) based on the functional severity of the mutations (complete or partial loss of function) and the number of affected alleles (monoallelic or biallelic) with mutations, and these classes were mapped on their clinical phenotypes. Results: The prevalence of heterozygous rare sequence variants in GNRHR was significantly higher in probands vs. controls (P < 0.01). Among the G1-G3 groups (homozygous subjects with successively decreasing severity and number of mutations), the hypogonadotropic phenotype related to their genetic load. In contrast, subjects in G4, with only monoallelic mutations, demonstrated a greater diversity of clinical phenotypes. Conclusions: In patients with GnRH deficiency and biallelic mutations in GNRHR, genetic burden defined by severity and dose is associated with clinical phenotype. In contrast, for patients with monoallelic GNRHR mutations this correlation does not hold. Taken together, these data indicate that as-yet-unidentified genetic and/or environmental factors may combine with singly mutated GNRHR alleles to produce reproductive phenotypes. 相似文献
42.
Gabriel Abarca Paulina L. Ríos Paula Povea Christopher Cerda-Cavieres Cesar Morales-Verdejo Juan L. Arroyo María B. Camarada 《RSC advances》2020,10(39):23165
The catalytic activity of nanoparticles of cobalt hydroxide supported on reduced graphene oxide, Co(OH)2|rGO, was studied for the decomposition of ammonium perchlorate (AP), the principal ingredient of composite solid propellants. Co(OH)2|rGO was synthesized by an in situ reduction method, which avoided the application of extremely high temperatures and harsh processes. rGO stabilized the nanoparticles effectively and prevented their agglomeration. The performance of Co(OH)2|rGO as a catalyst was measured by differential scanning calorimetry. Co(OH)2|rGO affected the high-temperature decomposition (HTD) of AP positively, decreasing the decomposition temperature of AP to 292 °C, and increasing the energy release to 290 J g−1. The diminution of the HTD of AP by Co(OH)2|rGO is in between the best values reported to date, suggesting its potential application as a catalyst for AP decomposition.Cobalt hydroxide nanoparticles supported on reduced graphene oxide increased the energy release and lowered the decomposition temperature of ammonium perchlorate. 相似文献
43.
Nir Lubezky Yaacov Goykhman Richard Nakache Ada Kessler Roni Baruch Paulina Katz Itzhak Kori Joseph M. Klausner Menahem Ben-Haim 《World journal of surgery》2013,37(6):1430-1437
Background
Graft pseudoaneurysm (PSA) following pancreatic transplantation (PT) is a rarely reported complication that has significant morbidity and mortality. Few case reports and small series of this complication exist.Methods
Retrospective review of files of 106 patients who underwent PT at the Tel-Aviv Sourasky Medical center between 1995 and 2010. Accessible asymptomatic patients (n = 35) were referred for graft PSA screening using ultrasound-Doppler.Results
Eight patients developed graft PSA (8 %). All had early posttransplant sepsis. PSA incidence among patients who had perioperative sepsis is 13 %. Three patients developed early postoperative PSA, presenting as massive abdominal bleeding requiring urgent laparotomy and graft resection. Five patients were diagnosed with late-onset graft PSA between 3 months and 11 years posttransplant: clinical presentations were massive gastrointestinal bleeding (n = 2), acute renal failure (n = 1), and asymptomatic finding on screening ultrasound-Doppler (n = 2, 6 % of screened patients).Conclusions
PSA following PT occurs in 8 % of patients. Perioperative infection is a risk factor. Early PSAs present as massive intra-abdominal bleeding. PSA may develop years posttransplant, may be asymptomatic, but late rupture is possible and presents as gastrointestinal bleeding. We recommend screening of patients at risk with ultrasound Doppler for early detection and treatment of asymptomatic PSAs. 相似文献44.
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46.
Paulina Misztak Patrycja Pańczyszyn-Trzewik Magdalena Sowa-Kućma 《Pharmacological reports : PR》2018,70(2):398-408
Major depressive disorder (MDD) represents approximately 40% of the disability caused by mental illnesses globally. The poorly understood pathophysiology and limited efficiency of pharmacological treatment (based primarily on the principles of the monoaminergic hypothesis) make depression a serious medical, public and socio-economical problem. An increasing number of studies suggest that epigenetic modifications (alterations in gene expression that are not due to changes in DNA sequence) in certain brain regions and neural circuits represent a key mechanism through which environmental factors interact with individual's genetic constitution to affect risk of mental disorders. Accordingly, chromatin-based epigenetic regulation seems to be a promising direction for the development of new, more effective antidepressant drugs. Recently, several inhibitors of histone deacetylases (HDAC) have been extensively studied in the context of antidepressant action. So far, none of them has been used to treat depression in humans due to the low selectivity for specific HDAC isoforms, and consequently, a risk of serious adverse events. In this review, we focus on the HDAC inhibitors (HDACi) with the greatest antidepressant efficacy and their activity in the preclinical studies. Moreover, we discuss their potential therapeutic usefulness in depression and the main limitations. 相似文献
47.
Vande Berg Perrine Ulaj Artida de Broqueville Graziella de Vos Marie Delire Bénédicte Hainaut Philippe Thissen Jean-Paul Stärkel Peter Komuta Mina Henry Paulina Lanthier Nicolas 《Obesity surgery》2022,32(4):1227-1235
Obesity Surgery - Metabolic dysfunction–associated fatty liver disease–related cirrhosis is possible at the time of bariatric surgery, complicated by further liver decompensation.... 相似文献
48.
Paulina Krzyszczyk Hwan June Kang Suneel Kumar Yixin Meng Maurice D. O'Reggio Kishan Patel Ivan S. Pires Martin L. Yarmush Rene S. Schloss Andre F. Palmer Franois Berthiaume 《Wound repair and regeneration》2020,28(4):493-505
Nonhealing wounds possess elevated numbers of pro‐inflammatory M1 macrophages, which fail to transition to anti‐inflammatory M2 phenotypes that promote healing. Hemoglobin (Hb) and haptoglobin (Hp) proteins, when complexed (Hb‐Hp), can elicit M2‐like macrophages through the heme oxygenase‐1 (HO‐1) pathway. Despite the fact that nonhealing wounds are chronically inflamed, previous studies have focused on non‐inflammatory systems, and do not thoroughly compare the effects of complexed vs individual proteins. We aimed to investigate the effect of Hb/Hp treatments on macrophage phenotype in an inflammatory, lipopolysaccharide (LPS)‐stimulated environment, similar to chronic wounds. Human M1 macrophages were cultured in vitro and stimulated with LPS. Concurrently, Hp, Hb, or Hb‐Hp complexes were delivered. The next day, 27 proteins related to inflammation were measured in the supernatants. Hp treatment decreased a majority of inflammatory factors, Hb increased many, and Hb‐Hp had intermediate trends, indicating that Hp attenuated overall inflammation to the greatest extent. From this data, Ingenuity Pathway Analysis software identified high motility group box 1 (HMGB1) as a key canonical pathway—strongly down‐regulated from Hp, strongly up‐regulated from Hb, and slightly activated from Hb‐Hp. HMGB1 measurements in macrophage supernatants confirmed this trend. In vivo results in diabetic mice with biopsy punch wounds demonstrated accelerated wound closure with Hp treatment, and delayed wound closure with Hb treatment. This work specifically studied Hb/Hp effects on macrophages in a highly inflammatory environment relevant to chronic wound healing. Results show that Hp—and not Hb‐Hp, which is known to be superior in noninflammatory conditions—reduces inflammation in LPS‐stimulated macrophages, and HMGB1 signaling is also implicated. Overall, Hp treatment on M1 macrophages in vitro reduced the inflammatory secretion profile, and also exhibited benefits in in silico and in vivo wound‐healing models. 相似文献
49.
Paulina Kurleto Agnieszka Skorupska-Król Elżbieta Broniatowska Katrina A. Bramstedt 《Clinical transplantation》2020,34(10):e14034
Non-directed living donors are individuals who donate a kidney to a recipient with whom they have neither a genetic nor emotional relationship. Israel legalized this type of donation in 2008. After this law was implemented, living donations significantly expanded. The aim of this article was to determine the motivations, characteristics, and perioperative experiences of non-directed living donors in Israel. Three online questionnaires (own questionnaire, Rosenberg Self-Esteem Scale (RSES), Rushton Self-Report Altruism Scale) were distributed to 180 Jewish kidney donors with the help of Matnat Chaim organization. One hundred and fifteen responses were received (69.3% response rate). The motivation for most donors (60%) was a strong willingness to help and a desire to do good. The majority of donors (78.3%) reported their health status as unchanged after donation; however, 16.5% experienced clinical problems (eg, wound infection, more pain than expected), and 5.2% experienced psychological complications. About 18% reported their health to improve after donation. Most (80%) inspired someone else to also become a kidney donor. This study breaks the myth that Jews do not support organ donation. In fact, their high level of altruism and their positive experience with donation has propelled the practice of non-directed donation in Israel. 相似文献
50.
Fausto Biancari Juha Saarnio Ari Mennander Linda Hypén Paulina Salminen Kari Kuttila Mikael Victorzon Camilla Böckelman Enrico Tarantino Olivier Tiffet Vesa Koivukangas Jon Arne Søreide Asgaut Viste Luigi Bonavina Halla Vidarsdóttir Tomas Gudbjartsson 《World journal of surgery》2014,38(4):902-909