Hussainwalls4113

One of the principal mechanisms of chemotherapy resistance in highly frequent solid tumors, such as colorectal cancer (CRC), is the decreased activity of drug transport into tumor cells due to low expression of important membrane proteins, such as solute carrier (SLC) transporters. Sequence complementarity is a major determinant for target gene recognition by microRNAs (miRNAs). Single-nucleotide polymorphisms (SNPs) in target sequences transcribed into messenger RNA may therefore alter miRNA binding to these regions by either creating a new site or destroying an existing one. miRSNPs may explain the modulation of expression levels in association with increased/decreased susceptibility to common diseases as well as in chemoresistance and the consequent inter-individual variability in drug response. In the present study, we investigated whether miRSNPs in SLC transporter genes may modulate CRC susceptibility and patient's survival. Using an in silico approach for functional predictions, we analyzed 26 miRSNPs in 9 SLC genes in a cohort of 1368 CRC cases and 698 controls from the Czech Republic. After correcting for multiple tests, we found several miRSNPs significantly associated with patient's survival. SNPs in SLCO3A1, SLC22A2 and SLC22A3 genes were defined as prognostic factors in the classification and regression tree analysis. In contrast, we did not observe any significant association between miRSNPs and CRC risk. To the best of our knowledge, this is the first study investigating miRSNPs potentially affecting miRNA binding to SLC transporter genes and their impact on CRC susceptibility or patient's prognosis.

What is the underlying neuropathology in a cynomolgus macaque model of functional hypothalamic amenorrhoea (FHA) and can it be normalized to restore ovulation?

Anovulatory monkeys exhibited increased hypothalamic norepinephrine (NE), kisspeptin and gonadotropin-releasing hormone (GnRH) in the early follicular phase, but administration of the NE reuptake inhibitor (NRI), reboxetine (REB), restored ovulation during stress and normalized NE, kisspeptin and GnRH.

Female cynomolgus macaques, like women, show individual reproductive sensitivity to modest psychosocial and metabolic stress. During stress, resilient females ovulate through two menstrual cycles whereas stress-sensitive (SS) macaques immediately cease ovulation. On Day 5 of a non-stressed menstrual cycle, resilient macaques have less NE synthesizing enzyme [dopamine β-hydroxylase (DBH)], kisspeptin and GnRH innervation of the medial basal hypothalamus but more endogenous serotonin than SS macaques. Stress increased DBH/NE, kisspeptin and GnRH but could be straightforward compared to current treatment protocols. The underlying neurobiology provides a compelling case for treating the origin of the pathology, i.e. elevated NE, rather than circumventing the hypothalamus altogether with gonadotropins, which have associated risks such as hyperstimulation syndrome or multiple births.

Portions of this study were supported by NIH grant HD062864 to C.L.B., NIH grant HD62618 to J.L.C. and C.L.B. and 1P51 OD011092 for the operation of the Oregon National Primate Research Center. There were no competing interests.

Portions of this study were supported by NIH grant HD062864 to C.L.B., NIH grant HD62618 to J.L.C. and C.L.B. and 1P51 OD011092 for the operation of the Oregon National Primate Research Center. There were no competing interests.Health literacy is considered by some as a determinant of health. Research suggests that different levels of health literacy may be associated with human immunodeficiency virus (HIV) knowledge and behaviour, including willingness to test. This study assessed the health literacy demands of existing Australia HIV prevention resources available online using a health literacy assessment and content analysis. Two reviewers assessed 66 resources using the Health Literacy INDEX. Sixty-one (92%) scored below 50%, with an average score of 35.5%. A coding frame was developed to conduct a content analysis of the resources excluding videos, multiple webpages and booklets (n = 52). We coded for six categories of knowledge HIV knowledge (100% of resources), transmission (96%), acquired immune deficiency syndrome (AIDS) knowledge (88%), testing (87%), consequence of infection (85%) and prevention (77%). We found that resources required a reading grade above grade 8, and very few resources considered audience appropriateness. There were missed opportunities to encourage HIV prevention or testing. PRGL493 datasheet Some resources used incorrect language to refer towards people living with HIV, and transmission and prevention messages were often inconsistent. Guidelines for developing HIV prevention resources are warranted to improve health literacy, accessibility and appropriateness of resources and ensure consistent messages and framing of HIV risk.The relationship between rs3746444 T>C single-nucleotide polymorphism (SNP) in microRNA (mir)-499 and risk of gastric cancer (GC) has been widely investigated. However, the association was still unconfirmed. Here, we first recruited 490 GC patients and 1476 controls, and conducted a case-control study. And we did not find any association between rs3746444 T>C SNP polymorphism and risk of GC. Subsequently, we conducted a meta-analysis to explore the association of mir-499 rs3746444 polymorphism with GC development. Two authors searched the PubMed and EMBASE databases up to October 15, 2019 independently. Finally, nine literatures involving 12 independent studies were included. In total, 3954 GC cases and 9745 controls were recruited for meta-analysis. link2 The results suggested that allele model, homozygote model and recessive model could increase the risk of overall GC (P = 0.002, 0.009 and 0.013, respectively). When we excluded the studies violated HWE, this association was also found in allele model (P = 0.020) and dominant model (P= 0.044). In subgroup analyses, we identified that rs3746444 SNP in mir-499 increased the risk of GC in Asians and gastric cardiac adenocarcinoma (GCA) subgroups. No significant bias of selection was found (all P>0.1). Test of sensitivity analysis indicated that our findings were stable. Additionally, we found that the power value was 0.891 in the allele model, suggesting the reliability of our findings. In summary, our analysis confirmed the association between rs3746444 and the risk of GC, especially in Asians and in patients with GCA.

Current consensus recommendations define small bowel strictures (SBS) in Crohn's disease (CD) on imaging as luminal narrowing with unequivocal upstream bowel dilation. The aim of this study was to 1) evaluate the performance of cross-sectional imaging for SBS diagnosis in CD using luminal narrowing with upstream SB dilation and luminal narrowing with or without upstream dilation, and 2) compare the diagnostic performance of CT and MR enterography (MRE) for SBS diagnosis.

One hundred and eleven CD patients (81 with pathologically confirmed SBS, 30 controls) who underwent CT and/or MRE were assessed. Two radiologists (R1, R2) blinded to pathology findings independently assessed the presence of luminal narrowing and upstream SB dilation. Statistical analysis was performed for a) luminal narrowing with or without SB upstream dilation ("possible SBS"), b) luminal narrowing with upstream SB dilation ≥3cm ("definite SBS").

Sensitivity for detecting SBS was significantly higher using "possible SBS" (R1, 82.1%; R2, 77.9%) compared to "definite SBS" (R1, 62.1%; R2, 65.3%; p<0.0001) with equivalent specificity (R1, 96.7%; R2, 93.3%; p>0.9). Using criterion "possible SBS", sensitivity/specificity were equivalent between CT (R1, 87.3%/93.3%; R2, 83.6%/86.7%) and MRE (R1, 75.0%/100%; R2 70.0%/100%). Using criterion "definite SBS", CT showed significantly higher sensitivity (78.2%) compared to MRE (40.0%) for R1 but not R2 with similar specificities (CT, 86.7%-93.3%; MRE, 100%).

SBS can be diagnosed using luminal narrowing alone without the need for upstream dilation. link3 CT and MRE show similar diagnostic performance for SBS diagnosis using luminal narrowing with or without upstream dilation.

SBS can be diagnosed using luminal narrowing alone without the need for upstream dilation. CT and MRE show similar diagnostic performance for SBS diagnosis using luminal narrowing with or without upstream dilation.

Memory impairment occurs in both HIV-associated neurocognitive disorders (HAND) and amnestic mild cognitive impairment (aMCI), the precursor to Alzheimer's disease (AD). Methods are needed to distinguish aMCI-associated from HAND-associated impairment in people with HIV (PWH). We developed a neuropsychological method of identifying aMCI in PWH and tested this method by relating AD neuropathology (β-amyloid, phospho-Tau) to aMCI versus HAND classification.

Seventy-four HIV+ cases (age 50-68) from the National NeuroAIDS Tissue Consortium had neurocognitive data within one-year of death and had data on β-amyloid and phospho-Tau pathology in frontal brain tissue. High aMCI risk was defined as impairment (<1.0 SD below normative mean) on two of four delayed recall or recognition outcomes from a verbal and non-verbal memory test (at-least one recognition impairment required). Differences in β-amyloid and phospho-Tau by aMCI and HAND classification were examined.

High aMCI risk classification was more common in the HAND (69.0%) versus no HAND (37.5%) group. β-amyloid pathology was 4.75 times more likely in the high versus low aMCI risk group. Phospho-Tau pathology did not differ between aMCI groups. Neither neuropathological feature differed by HAND status.

amnestic mild cognitive impairment criteria that include recognition impairment may help to detect AD-like cognitive/biomarker profiles among PWH.

amnestic mild cognitive impairment criteria that include recognition impairment may help to detect AD-like cognitive/biomarker profiles among PWH.The functional and numerical responses of Habrobracon hebetor (Say) were assessed over 30 sequential generations (G) on different densities (2, 4, 8, 16, 32, 64, and 128 fifth-instar larvae) of the Mediterranean flour moth, Ephestia kuehniella (Zeller). Seven tested generations (G2inf, G4inf, G6inf, G8inf, G10inf, G15inf, and G30inf) had already been naturally infected by a fungus species, whereas only the second generation (G2) had the colonies of both infected (G2inf) and uninfected (G2uninf) individuals. All infected generations, as well as the uninfected generation, showed a Type III functional response. A high variation was found in the handling times (Th) of the parasitoid through 30 sequential generations, and G10inf had the longest handling time. The shortest handling time and the maximum estimated attack rate (T/Th) were observed in G2inf. No significant difference in terms of the number of parasitized hosts was found among all infected generations, as well as between G2inf and G2uninf. Although the handling times in G2inf and G2uninf were close to each other, the attack coefficient of G2uninf was more than that of G2inf. The attack coefficient and handling time of infected generations increased from G2inf to G10inf and then decreased in the higher generations. The most plausible parameters of functional response of infected generations were observed in Ginf. A negative relationship between eggs laid and host densities was observed in the infected generations (G2inf, G4inf, G6inf, G8inf, and G10inf). G2uninf and, among infected generations, Ginf were the best generations for practical utilization in inundative release programs.