Total Study Group Research Articles

Relationship between postprandial lipemia and atherogenic factors in healthy subjects by considering gender differences

BackgroundPostprandial triglyceride concentrations are clinically significant and independent predictor of cardiovascular disease risk. The purpose of this study was to determine postprandial TG ranges in healthy subjects by considering gender differences. Secondly, assess the relationship between postprandial lipemia and atherogenic indicators. Finally, investigate the use of the postprandial 4h TG test instead of the area under the curve (AUC). MethodsPostprandial lipemia was investigated using the standardized oral fat tolerance test (OFTT) in 96 healthy subjects (45 female/51 male). Study group was categorized into tertiles based on AUC calculated using TG concentrations at fasting and 2, 4 and 6h after OFTT. Lipid, lipoproteins, apolipoproteins, LDL subfractions and oxidized LDL (oxLDL) were evaluated in tertiles in both sex groups. ResultsThe cut-off concentrations for postprandial 4-hour TG concentrations in female and male were 3.20 mmol/L and 4.59 mmol/L, respectively. We observed higher concentrations for atherogenic indicates like small dense-low density lipoprotein (sdLDL), oxLDL values in top tertiles for both groups (P < 0.05). Cohen's kappa coefficients for the agreement of AUC and 4h postprandial TG tests were 0.935, 0.970, 0.469 (P = 0.0001) in female, male and total study group, respectively. ConclusionDue to predominant effects of gender differences on postprandial lipemia, postprandial TG cut-off values for female and male subjects should be determined separately. Postprandial lipemia may be associated with atherogenic tendency by changing lipids, lipoproteins, sdLDL and oxLDL concentrations, especially in males. Four-hour postprandial TG concentrations emerged as a useful and reliable marker for evaluation of postprandial lipemia.

Luteinizing hormone and insulin resistance in menopausal patients with adrenal incidentalomas: The cause-effect relationship?

A high prevalence of insulin resistance (IR) has proven to manifest in patients with adrenal incidentalomas (AI). It has been demonstrated that an increase in IR is related to the size of tumourous masses; additionally, luteinizing hormone (LH)-dependent adrenal pathologies are well documented in patients with LH-responsive adrenal tumours occurring under conditions of physiologically elevated LH. We hypothesized that an association between LH and insulin might play a role in adrenal tumourigenesis and steroidogenesis. The aim of our study was to investigate the association between LH and IR; adrenal tumour size (ATS) and IR; LH and cortisol after the 1mg overnight dexamethasone test (1mg DST); and ATS and 1mg DST cortisol in AI patients. This was a case-control study conducted in the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Belgrade, Serbia. The total study group consisted of 105 menopausal women: 75 AI patients [27 with nonfunctional AI (NAI) and 48 with (possible) autonomous cortisol secretion ((P)ACS)] and 30 age-, BMI-, LH- and menopause duration-matched healthy control (HC) women. To estimate IR, we used homeostasis model assessment (HOMA-IR). Luteinizing hormone and ATS are in a significant positive correlation with HOMA-IR and 1mg DST cortisol in menopausal patients with AI and (P)ACS. Our data point to a possible cause-effect relationship between LH and insulin in patients with AI and (P)ACS adding to the body of evidence of their involvement in adrenal tumourigenesis and steroidogenesis.

The Combination of Quizartinib with Azacitidine or Low Dose Cytarabine Is Highly Active in Patients (Pts) with FLT3-ITD Mutated Myeloid Leukemias: Interim Report of a Phase I/II Trial

Background : FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in acute myeloid leukemia (AML) is associated with early relapse and poor survival. Quizartinib potently and selectively inhibits FLT3 kinase activity. In a phase I and II studies the composite response rate (CRR) was approximately 50% among patients with FLT3-ITD. There is in-vitro synergy between quizartinib and 5-AZA or LDAC. We hypothesize that adding quizartinib to a hypomethylating agent such as 5-azacitidine (AZA) or cytarabine may improve the response rate expected from the use of either agent alone. Objectives: The primary objective of phase I part is to determine the dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of the combination of quizartinib (AC220) with either AZA or low-dose cytarabine (LDAC); for phase II is to determine the clinical activity of both combinations. This planned interim analysis reports on the recommended phase II dose (RP2D) and first futility analysis. Methods: For phase I, patients with relapsed/refractory high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) or AML were eligible irrespective of FLT3 mutation and salvage status. For phase II, presence of FLT3-ITD is a requisite. Phase II enrollment is limited to patients >60 years with untreated MDS/CMML/AML, or any age receiving first salvage treatment. Additional eligibilities include performance status ECOG ≤2, adequate organ function, normal electrolytes (potassium, calcium and magnesium). Important exclusions include QTcF> 450 mSec, concomitant drugs that prolong QT/QTc interval or strong CYP3A4 inhibitors or inducers with the exception of antibiotics, antifungals, and antivirals that are used as standard of care. Treatment cycle is defined as 28 days. Treatment comprises of AZA 75 mg/m 2 subcutaneously (SQ) or intravenously (IV) for 7 days of every cycle (Days 1-7), or cytarabine 20 mg SQ twice daily for 10 days of every cycle (Days 1-10) along with quizartinib at two planned dose levels: 60 mg (dose level 1) or 90 mg orally daily (dose level 2) uninterrupted. Patients are assigned to AZA or LDAC arm by physician choice or slot availability. Planned accrual for each arm in phase 2 is 26 pts each and an ORR of ≥50% will be considered favorable. Accrual of 26 pts will give a 95% credible interval for overall response rate of (0.32, 0.68). The study will be stopped for toxicity (>30%) and/or futility (ORR Results: Twenty-six (Phase I=12, phase II=14) pts have been enrolled: 18 to AZA arm and 8 to LDAC arm. Median age is 62 years (range, 25-79 years), 7 (27%) are female. Cytogenetics are diploid=14, +8=2, -7=2, miscellaneous=6, 11q and t(8;21)= 1 each. Median number of prior therapies is 2 (range, 0-7), 7 patients received prior FLT3 inhibitor. For both schedules quizartinib 60 mg daily was identified as the recommended phase II dose (RP2D) based on emerging results from separate dose-finding study. Eighteen [5 in LDAC arm (63%) and 13 (72%) in AZA arm; all with FLT3-ITD mutation without D835 mutation] of 26 total pts (69%) have responded (CR=1/ CRp=3/ CRi=2/ MLFS=10/PR=1/HI=1). Among patients with FLT3-ITD (N=22), ORR is 82%. Four of 7 (57%) patients with prior FLT3 inhibitor exposure responded. Median number of days to respond is 57 days (range, 25-102 days). Among responders two patients died (MLFS=1, PR=1): one with gastro-intestinal bleeding and other with progressive pneumonia. Three additional responders have discontinued therapy for stem cell transplant (1), withdrawal of consent (1), and loss of response with emergence of D835 mutation (1). Nine responders (CR=1, CRi=1, CRp=1, PR=1, MLS=5) had >50% reduction of FLT3-ITD allelic burden and 2 additional pts (CR=1, CRi=1) had no detectable FLT3-ITD at response. Number of pts with treatment emergent grade 3/4 toxicities irrespective of attribution include hypokalemia (15), hypophosphatemia (5), hyponatremia (4), hypocalcemia (4), hyperbilirubinemia (3), increase in ALT (1), hypernatremia (1hyperglycemia (1), hypotension (1), QTcF prolongation (1, grade 3). Conclusion : Combination of quizartinib and AZA or LDAC is highly active among patients with AML/MDS/CMML with FLT3-ITD . Response rates appear higher than expected with either agent alone. Clinically significant QTcF prolongation is infrequent. Accrual to both arms of the current trial continues. Disclosures Cortes: Ambit Biosciences: Research Funding.

Aflibercept for Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in Germany: Twelve-Month Outcomes of PERSEUS

To explore real-world effectiveness of intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD) in Germany. A 24-month, prospective, noninterventional, noncontrolled, multicenter observational cohort study. Patients (n= 848) with nAMD treated with IAI. Patients (n= 988) were screened at 67 study sites. Therapeutic decisions were made by the treating physician. Primary end point analysis was performed after 12 months for the entire study cohort and for predetermined subgroups of treatment-naïve and previously treated patients. Additionally, outcomes with regular injection intervals (bimonthly after 3 monthly injections) were compared with those of patients with irregularities in their treatment regimen. The primary end point was the mean change in visual acuity (VA) from baseline after 12 months. Other key end points included the proportions of patients gaining 15 letters or more and patients with reading vision (≥70 letters). Furthermore, the number of injections, anatomic measurements, and safety data were recorded. Mean ± standard deviation VA improvement was 5.3±17.4 letters in treatment-naïve patients and-0.1±15.6 letters in previously treated patients (P ≤ 0.0001), and that of the total study group was 2.9±16.8 letters. Baseline VA was 53.4±17.9 letters for treatment-naïve patients, 52.9±18.4 letters for previously treated patients, and 53.2±18.1 letters for the total patient population. Treatment pattern was associated with VA outcome: best outcomes-an average VA gain of 8.0±17.7 letters-were seen in treatment-naïve patients in the regularly treated population, whereas irregularly treated, treatment-naïve patients achieved a mean VA gain of only 4.0±17.1 letters. Among previously treated patients, regular treatment also was associated with better outcomes (+3.1±10.7 vs.-1.1±16.8 letters). For the total study group, the mean VA gain was the following: regularly treated population, 6.1±15.6 letters; irregularly treated population, 1.5±17.1 letters (P= 0.008). No cases of endophthalmitis were observed during the first 12 months of the study. Adverse events were in line with the known safety profile of IAI. After 12 months of treatment with IAI, treatment-naïve patients showed substantial functional benefit, whereas previously treated patients maintained their VA. With regular IAI treatment, it seems that similar results as those in pivotal IAI studies can be achieved in routine clinical practice.

Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer.

Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case-control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case-control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93-3.47; P = 1.87 × 10-10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10-2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer increased bladder cancer risk particularly in never smokers.

Natural variation of the zygomaticomaxillary complex symmetry in normal individuals

ObjectiveThe study aim was to investigate variations in the symmetry of the zygomaticomaxillary complex (ZMC) in normal individuals. MethodComputed tomography datasets of 200 individuals without facial fractures were analyzed using a validated three-dimensional analysis technique. The absolute average distance (AD) and 90th percentile distance (NPD) were calculated, representing respectively the overall and maximum symmetry between bilateral ZMCs. ResultsThe mean AD and NPD of the total study group was 0.9 ± 0.3 mm (95% CI 0.3–2.3) and 1.7 ± 0.5 mm (95% CI 0.5–3.9), respectively. The mean AD and NPD in males were 1.0 ± 0.3 mm (95% CI 0.28–2.34) and 1.9 ± 0.5 mm (95% CI 0.5–3.9) versus 0.8 ± 0.3 mm (95% CI 0.4–1.7) and 1.6 ± 0.5 mm (95% CI 0.8–2.9), respectively, for females. A statistically significant difference between male and female was found for both AD and NPD (p < 0.01). The male population <40 years had a mean AD and NPD of 1.0 ± 0.3 mm and 1.8 ± 0.5 mm, which was not statistically significant when compared with males >40 years. ConclusionThe naturally occurring anatomic variation in ZMC symmetry described in this study is proposed as a benchmark for evaluating the amount of preoperative displacement and postoperative reduction of ZMC in trauma cases.

Investigating the association of rs2910164 with cancer predisposition in an Irish cohort.

IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA–mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort.MethodsThe study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22.ResultsThe total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98–1.46), P = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18–2.14), P = 0.002).ConclusionThe rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort.

The Relationship between Markers of Inflammation and Degeneration in the Central Nervous System and the Blood-Brain Barrier Impairment in Alzheimer’s Disease

It is known that YKL-40- a marker of glial inflammation, and VILIP-1- a marker of neuronal injury, reflect functional and structural changes in AD brains, although there is limited data concerning their potential influence on blood-brain barrier (BBB) homeostasis. Therefore, the aim of our study was to investigate the relationship between markers of inflammation and degeneration in the central nervous system (CNS) of patients with AD and mild cognitive impairment (MCI) as well as immunological response in CNS and BBB function. Cerebrospinal fluid (CSF) concentrations of proteins tested were determined in 45 AD patients, 18 MCI subjects, and 23 non-demented controls using ELISA method. CSF concentrations of YKL-40 were significantly higher in MCI and AD patients, whereas CSF levels of VILIP-1 were statistically higher in the AD group as compared to the subjects without cognitive deficits. Elevated concentrations of YKL-40 correlated significantly with increased albumin quotient and decreased Aβ42/40 ratio in AD patients and with IgG quotient in the total study group. We did not find a relationship between VILIP-1 and immunological parameters reflecting BBB dysfunction and humoral immune response. Our findings indicate that YKL-40 may contribute to decreased stability and increased permeability of BBB in AD patients. It is assumed that YKL-40 is implicated in the development of brain barriers, although its precise mechanism of action in the BBB disruption remains unrevealed. Further studies on larger groups of patients are required to confirm our hypothesis.

Relationship between obstructive sleep apnea syndrome and cognitive impairment and functional status after stroke

Objective:To analyze the correlation between obstructive sleep apnea syndrome (OSAHS) and cognitive impairment and functional status after stroke. Method:From February 2014 to September 2016, a total of 189 patients were included in the study, 33 patients with mild OSAHS were excluded, and finally 86 patients in the study group and 70 patients in the control group were included in the final analysis. The main indicators included the cognitive and functional status. Cognitive status was assessed by nine dimensions: vigilance, attention, memory, working memory, executive, language, insight, mental activity, psychomotor, and intelligence. Functional status was assessed using neurological status and functional independence. Secondary measures included sleepiness, fatigue, anxiety and depression, and sleep quality. Result:The age of the study group was higher than the control group, the BMI was higher than the control group, the average hospitalization time was longer than the control group, and all of the difference were statistically significant (all P<0.05). The total cognitive status of the two groups was significantly different, and the total cognitive status study group was significantly worse than in the control group (t=9.276, P=0.012). In the nine dimensions of cognitive ability, the study group's attention, execution, insight, mental adjustment and intelligence were lower than the control group, and the difference was statistically significant (P<0.05). The functional status of the study group was worse than that of the control group (t=38.094, P=0.000). There were no significant differences between the two groups in terms of sleepiness, fatigue, sleep quality, anxiety and depression (P>0.05). Conclusion:The cognitive impairment and functional status of stroke patients with OSAHS are significantly worse. OSAHS is a risk factor for poor prognosis in stroke patients.

Evaluation of Alvardo score in diagnosis of acute appendicitis

Background: Acute appendicitis is a common cause of abdominal pain for which a prompt diagnosis is rewarded by a marked decrease in morbidity and mortality. Right Iliac fossa pain is the hallmark of acute appendicitis until proven otherwise. Decision making in a case of acute appendicitis may be difficult, especially for junior surgeons. Hence, we aimed at analysing the Alvarado Score in patients with right iliac fossa pain.Methods: A prospective study involving 120 patients with right iliac fossa pain attending KIMS casualty during May 2015- April 2016 were included in the study. Results: The least was in the age group of 56 to 65 years (2%). Out of 120 patients, 84 were males (70%) and 36 were female (30%). The male to female ratio was 1:0.4. Patients with Alvarado score 7-9 (Group I) includes 60 male and 26 females (71% of total study group). Alvarado score 5-6 (Group II) includes 17 males,19 female (22% of total study group). Alvarado score 1-4 (Group III) includes 7 males, and 1 female (7% of total study group). In patients of Group I, among 60 males, 51 were confirmed with acute appendicitis. Among 26 females, 19 were confirmed with acute appendicitis, with a positive appendicectomy rate of 81.3% and negative appendicectomy rate 19.7%. The numbers of patients were highest in the age group 15 to 25 years (38%) followed by 36 to 45 years (30%).Conclusions: The Modified Alvarado scoring system was found to be highly effective in the diagnosis of the acute appendicitis in men and can be widely used to avoid expensive time consuming and non-readily available additional investigations. However, this system was not very effective in women. Therefore, ultra sound examination of abdomen and pelvis and diagnostic laparoscopy are also advised to minimize the high false negative rate in women which excludes common pelvic pathology that mimic clinically acute appendicitis.

6q25.1 (TAB2) microdeletion syndrome: Congenital heart defects and cardiomyopathy.

Congenital heart defects (CHD) are the most frequent type of congenital anomaly and are often associated with genetic and chromosomal syndromes. Haploinsufficiency of TAB2 (TGF-beta activated kinase 1/MAP3K7 binding protein 2) has been proposed to cause valvular and cardiac outflow tract structural abnormalities. In this study, we describe 13 newly identified individuals with microdeletions of chromosome 6q25.1 that involve TAB2. One of the patients in our study cohort has the smallest deletion yet reported, affecting only TAB2. These were compared to 27 other patients reported in the published literature or DECIPHER to have similar microdeletions, for a total study group of 40 patients. Our study shows that individuals with TAB2 deletions are predisposed to developing a primary cardiomyopathy with reduced systolic function, even in the absence of CHD. Our study cohort also shares a number of non-cardiac phenotypic findings: characteristic dysmorphic facial features, intrauterine growth restriction and/or postnatal proportionate short stature, hypotonia, developmental delay and/or intellectual disability, and connective tissue abnormalities. We conclude that a microdeletion of 6q25.1 that includes TAB2 causes a distinctive, multi-systemic syndrome. The 6q25.1 microdeletion syndrome should be considered in a patient with cardiomyopathy or a CHD, especially valve and/or atrial or ventricular septal abnormalities, and with phenotypic features described in this study. We recommend that patients with a TAB2 deletion be screened longitudinally for systolic heart failure, even if an initial echocardiogram is normal.

Association between month of birth and melanoma risk: fact or fiction?

Background Evidence on the effect of ultraviolet radiation (UVR) exposure in infancy on melanoma risk in later life is scarce. Three recent studies suggest that people born in spring carry a higher melanoma risk. Our study aimed at verifying whether such a seasonal pattern of melanoma risk actually exists. Methods Data from the population-based Cancer Registry Bavaria (CRB) on the birth months of 28 374 incident melanoma cases between 2002 and 2012 were analysed and compared with data from the Bavarian State Office for Statistics and Data Processing on the birth month distribution in the Bavarian population. Crude and adjusted analyses using negative binomial regression models were performed in the total study group and supplemented by several subgroup analyses. Results In the crude analysis, the birth months March-May were over-represented among melanoma cases. Negative binomial regression models adjusted only for sex and birth year revealed a seasonal association between melanoma risk and birth month with 13-21% higher relative incidence rates for March, April and May compared with the reference December. However, after additionally adjusting for the birth month distribution of the Bavarian population, these risk estimates decreased markedly and no association with the birth month was observed any more. Similar results emerged in all subgroup analyses. Conclusions Our large registry-based study provides no evidence that people born in spring carry a higher risk for developing melanoma in later life and thus lends no support to the hypothesis of higher UVR susceptibility during the first months of life.

Prevalence of valvular heart diseases and associated risk factors in Han, Uygur and Kazak population in Xinjiang, China.

BackgroundValvular heart diseases (VHD) is very common in clinical practice and has became the subject of growing attention in the field of cardiovascular medicine. Our aim was to assess the prevalence and correlates of VHD in the general population in Xinjiang, China.MethodsUsing a 4-stage stratified cluster random sampling method, a total of 14618 participants were recruited in the Cardiovascular Risk Survey (CRS) study. The participants’ personal information, medical history were assessed by questionnaire. VHD was diagnosed by transthoracic echocardiography. We carried out the statistical analysis utilizing SPSS Statistics version 19.0.ResultsIn the total study group, VHD was observed in 1397 (9.65%) individuals. The prevalence rates of VHD in Han, Uygur and Kazak group are 13.51%, 2.71% and 12.29% respectively. The prevalence rates of VHD increased strikingly with age (all P < 0.001). The results of multinomial regression analysis indicated that VHD were related to age in Han group, to age smoking and hypertension in Uygur group, to age and hypertension in Kazak group.ConclusionOur research provides a unique prevalence rate of VHD in Xinjiang natural population. The result suggests that VHD are notably common in this population (9.65%) and increase with age. There exists significant difference of prevalence rate between ethnics. The main risk factors of VHD are age, hypertension and smoking. Valvular heart diseases should be regarded as a serious and growing public-health problem.

Detection of Polyomavirus BK and JC in kidney Transplant Recipients

&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; objectives: To investigate the polyomaviruses (BK, JC) in asymptomatic kidney transplant recipients and healthy persons as control. It is one of the first reports on serological detection and molecular characterization that describes the circulation of polyomaviruses (BKV, JCV) have been done in Iraq recently. Methodology: The present study was designed as prospective case control study was done during the period from November 2015 to August 2016. Total of 97 serum and urine samples were collected randomly from 25 healthy control person and 72 renal transplant recipients, attending Iraqi Renal Transplantation Society. “New experimental indirect ELISA kit" had been designed and synthesized manually for detection Anti-JCV IgM and IgG, Urea and creatinine level had been measured for total study groups for estimation of renal functions. Results: All of the samples were submitted to a Nested-PCR. A significantly difference had been seen (P &lt; 0.01) of PyV was found in renal transplant patients 2(2.8%) in comparison to the control group 4(16.0%). JCV was detected in.6 (6.2%) samples (2 patients/ 4 controls).by conventional PCR, BKV was detected in 2(2.8%) of renal transplant group and not detected with any one of control group. result for IgM revealed positivity for 25(25.8%) out of 72cases of renal transplant subject and 8(8.2%) person out of 25control groups. for IgG the result show that 21(29.2%) out of 72 cases of renal transplant Subjects have a positive result for IgG but this antibody was not detected in the control. Recommendations: Success diagnosis required sensitive assay typically Nested-PCR to detect extremely low viral load present in potential kidney donor before access as a donor, Because of the potentially harmful effects of polyomavirus which may cause loss of the transplanted kidney&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Technology Trumping Sleep: Impact of Electronic Media and Sleep in Late Adolescent Students

The purpose of this research study was to explore with what impact evening media use interfered with either schoolwork and/or sufficient healthy sleep. In addition, the study examined with what impact there may be a compromise in students’ ability or aptitude for positive academic success, related to either lack of sleep or electronic media use. The participants were 89 high school and college students, ages 16 through 25, with median age of 18. Research was conducted using a secured online survey tool. Electronic habits, internet and social networking usage, sleep and rise times, daily sleepiness and perceptions were examined. College students were randomly sampled and participated in an in-depth, one-time survey. High school students participated in a weeklong nightly electronic sleep &amp; evening media use survey and journal. Data was obtained from anonymous and coded student responses and student and teacher surveys. The results of the study suggested that healthful adolescent sleep is indeed greatly compromised, during a time when the reverse is vitally important. Of students randomly sampled, all but one student owned a cell phone. In the total study group, a majority were smart phone owner-users (84%). Many high school participants slept with a cell phone or tablet in their bed (72%), and among college participants who regularly slept with cell phone, tablet, or laptop, this rose to 86%. Over half of these students continued to access and use their devices in bed for significant amounts of time prior to sleeping. Many of these even awakened after falling asleep to access or respond to electronic messaging. The research indicated that unhealthy sleep habits may be creating a generation of sleep-deprived individuals who may not be functioning at top capacity. Findings regarding a correlation between lack of sleep and quantified academic success are inconclusive, however, student perceptions indicate that they believe there is a relationship. Findings also suggest that all instructors of late adolescent students aged 16-25 may count on the fact of their student clientele owning and using mobile devices to access internet for social purposes. Students allow their social digital world to impede and compete with their academic time and biological sleep cycle. Instructors would be wise to appropriately channel the digital skills of this new generation of no longer-wired, but now “wi-fied” students. Therefore it is strongly suggested that teachers, parents, and medical personnel adopt and provide healthy guidelines for parents to use with pre-teens and teens, to facilitate and develop in the next generation of students some structure and means of protecting their health in the realms of electronics and sleep.

Galactooligosaccharides and substrate and energy metabolism, dietary intake and body composition

Aim: Obesity is associated with an altered composition of the gut microbiota. Prebiotics such as galactooligosaccharides (GOS) might modulate the gut microbiota composition beneficially and might have favorable metabolic effects in overweight and obese subjects. The aim of the study is to determine the effect of GOS on human substrate and energy metabolism, dietary intake and body composition in overweight and obese subjects. Methods: In a placebo-controlled, double-blind, randomized, parallel study, the effects of GOS were investigated in overweight and obese subjects. Weight-stable men and post-menopausal women between 40 and 75 years were included. Before and after the 12-week intervention period human substrate and energy expenditure were measured by indirect calorimetry. Subjects reported their dietary intake before, in week 6 and after the intervention period by completing a three-day weighed food diary. Self-reported level of physical activity was assessed using the validated SQUASH questionnaire. Changes in body composition were measured using a Dual-energy X-ray absorptiometry (DEXA) scan. A two-factor mixed analysis of variance (ANOVA) was performed to compare the intervention and placebo group. All analyses were performed blinded. Results: This interim analysis was performed after the data of 25 subjects was available. The data was blinded while analyzing. To maintain confidentiality of the data, the results of this interim analysis were not published. Conclusion: Only a part of the whole subject population was included in this interim analysis. The analyses in the total study group are required to draw more definite conclusions on the metabolic effects of GOS and to outline the potential of GOS to favorably affect host metabolism of overweight and obese subjects.

The Combination of Quizartinib with Azacitidine or Low Dose Cytarabine Is Highly Active in Patients (Pts) with FLT3-ITD Mutated Myeloid Leukemias: Interim Report of a Phase I/II Trial

Background: FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in acute myeloid leukemia (AML) is associated with early relapse and poor survival. Quizartinib inhibits FLT3 kinase activity potently and selectively. In phase I and II studies, the composite response rate (CRR) was approximately 50% among patients with FLT3-ITD. There is in-vitro synergy between quizartinib and 5-AZA or LDAC. We hypothesize that adding quizartinib to a hypomethylating agent- such as 5-azacitidine (AZA) -or to cytarabine may improve the response rate expected from the use of either agent alone.Objectives: The primary objective of phase I is to determine dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of combination of quizartinib with either AZA or low-dose cytarabine (LDAC); for phase II is to determine the clinical activity of both combinations. This planned interim analysis reports on the recommended phase II dose (RP2D) and first futility analysis.Methods: For phase I, pts with relapsed/refractory high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) or AML were eligible irrespective of FLT3 mutation and salvage status. For phase II: presence of FLT3-ITD is a requisite, pts must be >60 years with untreated MDS/CMML/AML or any age receiving first salvage treatment. Other requisites: performance status ECOG ≤2, adequate organ function and normal electrolytes (potassium, calcium and magnesium). Important exclusions include: QTcF> 450 msec, administration of drugs that prolong QT/QTc interval or strong CYP3A4 inhibitors or inducers; with the exception of antibiotics, antifungals, and antivirals that are used as standard of care.Treatment cycle is 28 days and comprises of AZA 75 mg/m2 subcutaneously (SQ) or intravenously (IV) for 7 days of every cycle, or cytarabine 20 mg SQ twice daily for 10 days of every cycle along with quizartinib at two planned dose levels: 60 mg (dose level 1) or 90 mg orally daily (dose level 2), uninterrupted. Patients are assigned to AZA or LDAC arm by physician choice or slot availability. Planned accrual for each arm in phase II is 26 pts each and an ORR of ≥50% will be considered favorable. Accrual of 26 pts will give a 95% credible interval for ORR of (0.32, 0.68). The study will be stopped for toxicity (>30%) and/or futility (ORR <50%) at interim analysis for each arm.Results: Fifty-two (Phase I=12, phase II=40) pts have been enrolled: 38 to AZA arm and 14 to LDAC arm. Median age is 67 years (range, 23-83 years), 24 (46%) are female. Cytogenetics are diploid=24, +8=5, monosomy 7=3, miscellaneous=17, 11q=2 and t(8;21)= 1. Median number of prior therapies is 1 (range, 0-7); 7 patients had received prior FLT3 inhibitor: sorafenib (5), crenolanib (1), quizartinib (1). For both combinations quizartinib 60 mg daily was identified as the recommended phase II dose (RP2D).Thirty-five Pts [8 in LDAC arm (23%) and 27 in AZA arm (77%)] of total 52 have responded with ORR 67 % (CR=8, CRp=7, CRi=18, PR=2); all with FLT3-ITD mutation without D835 mutation. ORR is 73% among pts with FLT3-ITD (N=48). Three of eight pts (38%) with prior FLT3 inhibitor exposure responded. Median time to response is 35 days (range, 14-187days). Among responders, two pts died (in CRi=1, PR=1): one with GI bleed and one with progressive pneumonia. Twelve responders discontinued therapy: 11 to receive a SCT and 1 due to loss of response with emergence of D835 mutation. Fifteen responders (CR=2, CRi=8, CRp=3, PR=2) had >50% reduction of FLT3-ITD allelic burden and eight additional pts (CR=5, CRi=1, CRp=2) had no detectable FLT3-ITD at response. The median survival was: 14.8 mo for the total study group: 7.5 mo for LDAC arm and not reached for AZA arm; median EFS has not been reached for either arm (Figure). Treatment emergent grade 3/4 toxicities irrespective of attribution include hypokalemia (15), hypotension (7), hypophosphatemia (7), hyponatremia (7), hypocalcemia (7), hyperbilirubinemia (1), elevated ALT (5), hypernatremia (2) hyperglycemia (1), QTcF prolongation (1, grade 3).Conclusion: Combination of quizartinib and AZA or LDAC is highly active among patients with AML/MDS/CMML with FLT3-ITD mutation in absence of D835 mutation. Response rates appear higher than expected with either agent alone. Clinically significant QTcF prolongation is infrequent. Accrual to the study continues. [Display omitted] DisclosuresJabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Konopleva:Calithera: Research Funding; Cellectis: Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.

Potential selection effects when estimating associations between the infancy peak or adiposity rebound and later body mass index in children.

This study aims to evaluate a potential selection effect caused by exclusion of children with non-identifiable infancy peak (IP) and adiposity rebound (AR) when estimating associations between age and body mass index (BMI) at IP and AR and later weight status. In 4744 children with at least 4 repeated measurements of height and weight in the age interval from 0 to 8 years (37 998 measurements) participating in the IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants)/I.Family cohort study, fractional polynomial multilevel models were used to derive individual BMI trajectories. Based on these trajectories, age and BMI at IP and AR, BMI values and growth velocities at selected ages as well as the area under the BMI curve were estimated. The BMI growth measures were standardized and related to later BMI z-scores (mean age at outcome assessment: 9.2 years). Age and BMI at IP and AR were not identifiable in 5.4% and 7.8% of the children, respectively. These groups of children showed a significantly higher BMI growth during infancy and childhood. In the remaining sample, BMI at IP correlated almost perfectly (r⩾0.99) with BMI at ages 0.5, 1 and 1.5 years, whereas BMI at AR correlated perfectly with BMI at ages 4-6 years (r⩾0.98). In the total study group, BMI values in infancy and childhood were positively associated with later BMI z-scores where associations increased with age. Associations between BMI velocities and later BMI z-scores were largest at ages 5 and 6 years. Results differed for children with non-identifiable IP and AR, demonstrating a selection effect. IP and AR may not be estimable in children with higher-than-average BMI growth. Excluding these children from analyses may result in a selection bias that distorts effect estimates. BMI values at ages 1 and 5 years might be more appropriate to use as predictors for later weight status instead.

Association between month of birth and melanoma risk: fact or fiction?

Evidence on the effect of ultraviolet radiation (UVR) exposure in infancy on melanoma risk in later life is scarce. Three recent studies suggest that people born in spring carry a higher melanoma risk. Our study aimed at verifying whether such a seasonal pattern of melanoma risk actually exists. Data from the population-based Cancer Registry Bavaria (CRB) on the birth months of 28 374 incident melanoma cases between 2002 and 2012 were analysed and compared with data from the Bavarian State Office for Statistics and Data Processing on the birth month distribution in the Bavarian population. Crude and adjusted analyses using negative binomial regression models were performed in the total study group and supplemented by several subgroup analyses. In the crude analysis, the birth months March-May were over-represented among melanoma cases. Negative binomial regression models adjusted only for sex and birth year revealed a seasonal association between melanoma risk and birth month with 13-21% higher relative incidence rates for March, April and May compared with the reference December. However, after additionally adjusting for the birth month distribution of the Bavarian population, these risk estimates decreased markedly and no association with the birth month was observed any more. Similar results emerged in all subgroup analyses. Our large registry-based study provides no evidence that people born in spring carry a higher risk for developing melanoma in later life and thus lends no support to the hypothesis of higher UVR susceptibility during the first months of life.

Assessment of Emerging Adult Women for Poly Cystic Ovarian Syndrome Symptoms

Introduction: Polycystic Ovary Syndrome (PCOS) is a very heterogeneous syndrome both in its clinical presentation and laboratory manifestations. Weight loss is feasible in adolescents with PCOS and significant improvements in BMI, Waist circumference and menstrual function can be achieved. Objective: To carry out the assessment of PCOS symptoms of selected emerging adult women and to identify samples at risk of PCOS. Materials and Methods: A prospective observational design was adopted and the sampling method used in this study is a non-probability sampling technique. Study was conducted for the duration of three months from November 2013 to February 2014 and 231 emerging adult women participated in this study. A questionnaire having the details of menstrual history and features of hyperandrogenism was collected from emerging adult women. Findings: The mean, age, height, weight and the body mass index was found to be, 18.86 ± 1.4 years,156.04 ± 7.75 cms, 52.86 ± 9.7 kg and 21.60 ± 3.55 (kg/m 2 ). 95 (41.1%) emerging adult women reported significant weight gain for the past two months. Among the total study group 87 (37.6%) emerging adult women were categorised as risk category and the rest 144 (62.3%) were not having any symptoms related to PCOS and were considered as normal emerging adult women. 24 women were having irregular menstrual cycle (22 having eight or fewer periods per year and two having more than 12 periods per year). 54 (23.3%) emerging adult women are with acne problem. Hirsutism was found among 27 (11.6%). Five (2.1%) of the subjects were having both acne and hirsutism were belonged to the risk group. Among the selected emerging adult women three percent had heavy bleeding were categorised under risk category. 48 percent of the selected emerging adult women did not do any physical activity, of them 17.7% belonged to 'at risk' category. Applications/Improvements: Based on severity of the condition, 74 subjects (32%) were categorised as risk subjects, among the total 87 emerging adult women who were predicted to have PCOS. It is preferable to follow these emerging adult women and repeat the evaluation for the exact diagnosis of PCOS.