Correlation Between Number of Retrieved Oocytes and Pregnancy Rate After \u3cem\u3eIn Vitro\u3c/em\u3e Fertilization/Intracytoplasmic Sperm Infection

The implementation of safe and maximally effective ovarian stimulation is a major aim for in vitro fertilization (IVF) teams. The goal of controlled ovarian hyperstimulation (COH) is to supply enough oocytes with normal maturation to insure the consequent biological procedures. A variety of different stimulation protocols have been suggested and an individual selection of the correct stimulation protocol is mandatory. The aim of the present study is to evaluate the correlation between number of retrieved oocytes and clinical pregnancy rate (CPR) after IVF or intracytoplasmic sperm injection (ICSI) procedures. We reviewed 1017 cycles in a total of 975 patients. The study results clearly demonstrate that the aspiration of less than 5 oocytes significantly reduced pregnancy rate. The aspiration of a large number of oocytes (\u3e15) does not lead to an increase of the treatment effect and, at the same time, increases the risk of ovarian hyperstimulation syndrome. The major goal is to obtain 5-15 oocytes as a gold standard , connected to optimal pregnancy rate after assisted reproduction (ART)

Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism That Increases Risk of Docetaxel-Induced Neuropathy

Purpose Discovery of single nucleotide polymorphisms (SNPs) that predict a patient\u27s risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with docetaxel-induced neuropathy and mechanistically validate these associations in preclinical models of drug-induced neuropathy. Experimental Design A genome-wide association study was conducted in metastatic castrate-resistant prostate cancer patients treated with docetaxel, prednisone and randomized to bevacizumab or placebo on CALGB 90401. SNPs were genotyped on the Illumina HumanHap610-Quad platform followed by rigorous quality control. The inference was conducted on the cumulative dose at occurrence of grade 3+ sensory neuropathy using a cause-specific hazard model that accounted for early treatment discontinuation. Genes with SNPs significantly associated with neuropathy were knocked down in cellular and mouse models of drug-induced neuropathy. Results 498,081 SNPs were analyzed in 623 Caucasian patients, 50 (8%) of whom experienced grade 3+ neuropathy. The 1000 SNPs most associated with neuropathy clustered in relevant pathways including neuropathic pain and axonal guidance. A SNP in VAC14 (rs875858) surpassed genome-wide significance (p=2.12×10-8 adjusted p=5.88×10-7). siRNA knockdown of VAC14 in stem cell derived peripheral neuronal cells increased docetaxel sensitivity as measured by decreased neurite processes (p=0.0015) and branches (p\u3c0.0001). Prior to docetaxel treatment VAC14 heterozygous mice had greater nociceptive sensitivity than wild-type litter mate controls (p=0.001). Conclusions VAC14 should be prioritized for further validation of its potential role as a predictor of docetaxel-induced neuropathy and biomarker for treatment individualization

The distribution of standard deviations applied to high throughput screening

High throughput screening (HTS) assesses compound libraries for “activity” using target assays. A subset of HTS data contains a large number of sample measurements replicated a small number of times providing an opportunity to introduce the distribution of standard deviations (DSD). Applying the DSD to some HTS data sets revealed signs of bias in some of the data and discovered a sub-population of compounds exhibiting high variability which may be difficult to screen. In the data examined, 21% of 1189 such compounds were pan-assay interference compounds. This proportion reached 57% for the most closely related compounds within the sub-population. Using the DSD, large HTS data sets can be modelled in many cases as two distributions: a large group of nearly normally distributed “inactive” compounds and a residual distribution of “active” compounds. The latter were not normally distributed, overlapped inactive distributions – on both sides –, and were larger than typically assumed. As such, a large number of compounds are being misclassified as “inactive” or are invisible to current methods which could become the next generation of drugs. Although applied here to HTS, it is applicable to data sets with a large number of samples measured a small number of times

NOTES ON VIТAMINS B1 AND С LEVEL ALTERATION IN ТНЕ BLOOD AND URINE OF SEAMEN, WORКING UNDER CONDIТIONS OF ЕLЕVAТЕD TEMPERATURE

In view of the great importance of vitamins В1 аnd С during intense metabolism of substances, observed in heavy physical work under conditions of elevated environmental temperature, wе set ourseles the task to investigate their level in blооd and urine of seamen working under heavy temperature conditions.The review of available literature sources reveals а great paucity of informations on the question. The vit. С content in the urine is investigated of seamen making part of the personnel of аn overseas ship. It is found out that eпgineering personnel displays about 50 % increase of its level, а fact indicating overexpenditure of the vitamin. The blооd levels of vit. С and vit. В1 content аrе not studied. The level of vit. С in the urine is studied also in nonacclimatized population of not climate regions, but in this case as well, investigations involve merely changes in the vit С content. The level of vit. С in the blоod of workers from high temperature shops is established at about 0,3 mg% lower than the normal. Other authors prove the effect of the overheating factor on the ground of clinical observations merely

Laparoscopic Surgery for Adrenal Tumors

Introduction: In recent years, laparoscopic adrenalectomy has been established as a widely used method of surgical treatment of adrenal tumors.Materials and Methods: In the period from 2006 to 2015, 64 patients aged 8 to 65 with adrenal gland tumors were operated on laparoscopically, including five patients with a bilateral localization. Preoperative diagnostics was conducted in collaboration with the Department of Endocrinology and Metabolic Diseases at the University Hospital `St. Marina`.Results: 64 patients underwent laparoscopic adrenalectomy. Intraoperative hypertensive crisis of up to RR 300/120 mmHg occurred in three patients. Four conversions in total were performed. Analysis of the results found a reduced need for analgesia, early rehabilitation of the patient, shortened hospital stay and the morbidity and mortality rate, and the rate of complications were comparable with these of an open adrenalectomy.Conclusion: Surgical treatment is the only option for radical treatment in patients withadrenal tumors. Laparoscopic adrenalectomy should be considered as a method of choice

Virtual Colonoscopy - Results in the Diagnostics of Colorectal Tumors

Introduction: Colorectal cancer (CRC) is the second most common malignancy in women and the most common one in men in the world. In Bulgaria, the incidence of new cases of colorectal cancer increases with each year. The gold standard in the diagnostic of colorectal cancer is endoscopic colonoscopy (EC) and over the past 10 years virtual colonoscopy (VC) has been established as a sensitive and accurate method for screening and diagnostics in patients with colorectal cancer.Aim: We performed a retrospective study including patients with colorectal neoplasms who underwent both endoscopic and virtual colonoscopy.Materials and Methods: 190 patients in total, who underwent both EC and VC from 2009 to 2015 in UMHAT `St. Marina`, were included in the study. We analyzed the indications for VC, its diagnostic value regarding tumor type, size, and localization.Results: Virtual colonoscopy was able to detect lesions in 180 of the patients. The most common indications were gastrointestinal bleeding, abdominal pain, and anaemia. The specificity and sensitivity were 94% and 98%, respectively. The results from EC and VC were comparable (p>0.05). Conclusion: Virtual colonoscopy is an established diagnostic method with high specificity and sensitivity and plays a significant role in the diagnosis and screening of colorectal carcinoma. VC is a non-invasive, painless diagnostic method and does not require sedation. It is useful as a omplementary method to EC and in cases where EC is not allowed

Laparoscopic Surgery for Hiatal Hernia

Introduction: The laparoscopic surgical treatment of hiatal hernia has lead to an improvement of the surgical results and nowadays it is accepted as the standard approach. Through the years the technique has evolved and several modifications were introduced. Aim: We present a retrospective study of 260 consecutive patients, operated on from 2001 to 2015 at the Department of General and Operative surgery, UMHAT `St. Marina` - Varna, Bulgaria.Results: Hiatal hernia types included axial hernia (n=67, 26%), paraesophageal hernia (n=13, 5%), mixed type (n=104, 40%), giant hiatal hernia (n=76, 29%). Overall, 215 (82.7%) patients had Nissen fundoplication and 45 (17.3%) had partial fundoplication. All patients underwent a posterior repair of the crura and 38 (14.6%) - additional anterior suture. Esophageal shortening of different severity was identified in 79 (30.4%) patients. Excellent results were achieved in 95%. The shortened esophagus is considered an important factor for hiatal hernia recurrence. Conclusion: The laparoscopic hiatal hernia repair has been proven as a feasible technique with excellent results, minimal morbidity and mortality with growing popularity amongst the patients. Esophageal lengthening procedures should be considered in selected groups of patients