Sonic Hedgehog Agonist Protects Against Complex Neonatal Cerebellar Injury

The cerebellum undergoes rapid growth during the third trimester and is vulnerable to injury and deficient growth in infants born prematurely. Factors associated with preterm cerebellar hypoplasia include chronic lung disease and postnatal glucocorticoid administration. We modeled chronic hypoxemia and glucocorticoid administration in neonatal mice to study whole cerebellar and cell type-specific effects of dual exposure. Chronic neonatal hypoxia resulted in permanent cerebellar hypoplasia. This was compounded by administration of prednisolone as shown by greater volume loss and Purkinje cell death. In the setting of hypoxia and prednisolone, administration of a small molecule Smoothened-Hedgehog agonist (SAG) preserved cerebellar volume and protected against Purkinje cell death. Such protective effects were observed even when SAG was given as a one-time dose after dual insult. To model complex injury and determine cell type-specific roles for the hypoxia inducible factor (HIF) pathway, we performed conditional knockout of von Hippel Lindau (VHL) to hyperactivate HIF1α in cerebellar granule neuron precursors (CGNP) or Purkinje cells. Surprisingly, HIF activation in either cell type resulted in no cerebellar deficit. However, in mice administered prednisolone, HIF overactivation in CGNPs resulted in significant cerebellar hypoplasia, whereas HIF overactivation in Purkinje cells caused cell death. Together, these findings indicate that HIF primes both cell types for injury via glucocorticoids, and that hypoxia/HIF + postnatal glucocorticoid administration act on distinct cellular pathways to cause cerebellar injury. They further suggest that SAG is neuroprotective in the setting of complex neonatal cerebellar injury.     

Effect of nasal mometasone furoate on the nasal and nasopharyngeal flora

Objective

Mometasone furoate (MF) is one of the commonly used topical steroids, particularly for patients with allergic rhinitis. However, its effect on the colonization of bacteria that may cause superinfections by suppressing the local immunity is not known. Thus, we investigated the effect of MF use on the nasal and nasopharyngeal microbial flora.

Materials and methods

Swab samples were taken from 35 patients who required MF monotherapy, just before and after one month of the treatment. Samples were maintained in Stuart's medium. Each swab was transferred to 1 ml of a sterile saline solution, then into the standard agar. After incubation under 5% carbon dioxide at 37 °C, colony number was detected per ml.

Results

Colony counts of nasal or nasopharyngeal microbial flora did not show any statistically significant alteration with one month use of MF. However, an increase in potential pathogens as well as normal flora bacteria was determined in five of the patients and six patients acquired new nasopharyngeal potential pathogens, mostly Moraxella catarrhalis, Pseudomonas aeruginosa and Staphylococcus aureus, following the use of MF.

Conclusion

The use of MF for one month did not statistically significantly change the nasal and nasopharyngeal flora. This study indicates that MF could be increase the colonization of the potential pathogens in some of the patients at the subclinical level particularly in the nasopharyngeal area.     

Annular Plaques on the Tongue: What Is Your Diagnosis?

Geographic tongue is an inflammatory disorder of the tongue characterized by asymptomatic erythematous patches with serpiginous borders. Candidiasis of the tongue may be confused with geographic tongue. A 63-year-old male patient with painful white annular lesions localized to the left side of his tongue is presented. He applied topical corticosteroid and antiinflammatory agents, but his lesions did not respond to those therapies. Using direct mycologic examination and culture, the patient was diagnosed with candidiasis. After systemic and topical antifungal therapy, clinical improvement was observed. With this case, the clinical forms of oral candidiasis were discussed, and it was suggested that the clinical presentation of mucosal candidiasis may vary according to the stage of infection and individual immunity.     

How useful is rectal endosonography in the staging of rectal cancer?

It is essential in treating rectal cancer to have adequate preoperative imaging,as accurate staging can influence the management strategy,type of resection,and candidacy for neoadjuvant therapy.In the last twenty years,endorectal ultrasound(ERUS) has become the primary method for locoregional staging of rectal cancer.ERUS is the most accurate modality for assessing local depth of invasion of rectal carcinoma into the rectal wall layers(T stage) .Lower accuracy for T2 tumors is commonly reported,which could ...     

Experience of a single center with congenital hepatic fibrosis:A review of the literature

Congenital hepatic fibrosis(CHF) is an autosomal recessive inherited malformation defined pathologically by a variable degree of periportal fibrosis and irregularly shaped proliferating bile ducts.It is one of the fibropolycystic diseases,which also include Caroli disease,autosomal dominant polycystic kidney disease,and autosomal recessive polycystic kidney disease. Clinically it is characterized by hepatic fibrosis,portal hypertension,and renal cystic disease.CHF is known to occur in association with a ran...     

Intra-sessional and inter-sessional variability of multifocal electroretinogram

The aim of this study was to investigate the intra-sessional and inter-sessional variability of the multifocal electroretinogram (mfERG). Right eyes of 20 healthy adult subjects with uncorrected visual acuity of 1.0 were studied. mfERG recordings were obtained in two sessions by using jet corneal electrodes. The responses were averaged over five retinal regions, the central hexagon (CH: 0.0–2.3°) and four concentric rings [ring 1 (R1: 2.3–7.4°), ring 2 (R2: 7.4–12.0°), ring 3 (R3: 12.0–19.4°), and ring 4 (R4: 19.4–30.0°)]. In the first session, recordings were repeated while the electrodes stayed in place (the first and the second recordings). Second sessions (third recordings) were performed 1 week later. Individual coefficient of variation (CV; standard deviation/mean) for P1 and N1 amplitudes and implicit times were calculated for the first to second and first to third recordings to assess intra-sessional and inter-sessional variability, respectively, and were evaluated by Wilcoxon-paired samples test. Regarding implicit time and amplitude of mfERG recordings, there was no significant difference between the first to second and first to third recordings (P > 0.05, Bonferroni-corrected Wilcoxon test). CV values significantly decreased with eccentricity in both intra-sessional and inter-sessional comparisons (P < 0.05, Wilcoxon test). However, partial ring averaging showed no significant difference (P > 0.05) between CV values for single hexagons in each ring. Intra-sessional CV values were significantly lower than corresponding inter-sessional values (P < 0.05, Wilcoxon test). Our results support the importance of electrode replacement on variability. The increased number of hexagons that are averaged is the main factor that explains the lower variability in the more peripheral rings.     

Potential Role of Lycopene in the Treatment of Hepatitis C and Prevention of Hepatocellular Carcinoma

Hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) are growing health problems around the world. Oxidative stress plays a significant role in the initiation and progression of hepatocellular damage and possibly in the development of HCC in HCV infected patients. In vitro, animal and clinical studies suggest that lycopene, a nonprovitamin A carotenoid and a potent antioxidant, may attenuate the liver injury and possibly prevent the development of HCC. In this article, we discuss the relationship between HCV infection and oxidative stress and review the potential role of lycopene in the treatment of HCV and prevention of HCC.     

The Relationship Between Eight GWAS‐Identified Single‐Nucleotide Polymorphisms and Primary Breast Cancer Outcomes

Background.

Several single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified through genome-wide association studies (GWAS). We investigated whether eight risk SNPs identified in GWAS were associated with breast cancer disease-free survival (DFS) and overall survival (OS) rates.

Patients and Methods.

A cohort of 739 white women with early-stage breast cancer was genotyped for eight GWAS-identified SNPs (rs2981582, rs1219648 [FGFR2], rs3803662, rs12443621, rs8051542 [TOX3], rs999737 [RAD51L1], rs6504950 [17q23], and rs4973768 [3p24]). Relationships between SNPs and breast cancer outcomes were evaluated using Cox proportional hazard regression models. The cumulative effects of SNPs on breast cancer outcomes were assessed by computing the number of at-risk genotypes.

Results.

At a median follow-up of 121 months (range: 188–231 months) for survivors, 237 deaths (32%) and 186 breast cancer events (25%) were identified among the 739 patients. After adjusting for age, clinical stage, and treatment, rs12443621 (16q12; p = .03) and rs6504950 (17q23; p = .008) were prognostic for OS but not DFS. A higher risk for death was also found in the multivariable analysis of patients harboring three or four at-risk genotypes of the GWAS SNPs compared to patients carrying two or less at-risk genotypes (hazard ratio: 1.60, 95% confidence interval: 1.23–2.24; p = .0008).

Conclusion.

The study results suggest that previously identified breast cancer risk susceptibility loci, rs12443621 (16q12) and rs6504950 (17q23), may influence breast cancer prognosis or comorbid conditions associated with overall survival. The precise molecular mechanisms through which these risk SNPs, as well as others that were not included in the analysis, influence clinical outcomes remain to be determined.