Tag Archives: pikfyve inhibitor

br Conclusion br Conflict of interest br Acknowledgements The author


Conflict of interest

The author would like to thank the College of Dentistry Research Centre and Deanship of Scientific Research at King Saud University, Saudi Arabia for supporting this research project.

Life expectancy increased steadily worldwide, from 46.9years in the 1950s to 68.7years by 2010 (United Nations, 2012). The increase in life expectancy for Saudi Arabia was even greater for the same period (41.9years in the 1950s to 74.3years by 2010) (United Nations, 2012). Moreover, the percentage of the Saudi population aged pikfyve inhibitor 60years and older is projected to reach 25.3% by 2050, compared to just 5.6% in 1950 (United Nations, 2012). Clearly the oral health care needs of elderly Saudi Arabians will increase in the coming years, and epidemiological surveys to identify these needs are needed. Surveys based on only clinical data need to be supplemented by those based on biopsy records, as both are necessary to adequately define oral health care needs. Additionally, records based on histological diagnosis are generally considered more accurate than those based on clinical diagnosis.
Geriatric mucosa is marked by decreased epithelial thickness, decreased synthesis of collagen by connective tissue cells, and increased vascular sclerosis, all of which are likely to result in decreased tissue regeneration, loss of elasticity, and decreased disease resistance (Breustedt, 1983; Vigild, 1987). A number of epidemiologic studies (often pikfyve inhibitor in design and presentation of results) on the oral mucosal disease of the elderly (van Wyk et al., 1977; Fleishman et al., 1985; Ekelund, 1988; Hoad-Reddick, 1989; Kaplan and Moskona, 1990; Corbet et al., 1994; Nevalainen et al., 1997; Reichart, 2000; Lin et al., 2001; Garcia-Pola Vallejo et al., 2002; Jainkittivong et al., 2002; Espinoza et al., 2003) have been published in the last 3 decades. Most of these studies were based on clinical examination of institutionalized or home-based elderly people, or were done in the context of denture-related oral pathologies. There have also been a number of studies that analyzed the prevalence of oral lesions in the elderly based on oral tissue biopsies submitted for pathology (Kononen et al., 1987; Skinner and Weir, 1987; Scott and Cheah, 1989; Correa et al., 2006; Franklin and Jones, 2006; Muzyka et al., 2009; Carvalho Mde et al., 2011). Owing to the paucity of data from either clinical examinations or oral biopsies from Saudi Arabia, phylum study was aimed at surveying soft-tissue biopsies in patients over age 60 who were diagnosed in the biopsy service of a teaching hospital over a 30year period, comparing these data with similar studies done in other parts of the world. Soft-tissue pathologies were chosen because these are usually the most common and the most clinically significant category of oral lesions in the elderly (Correa et al., 2006; Muzyka et al., 2009).

Materials and methods
The biopsies included in this study were those diagnosed between 1984 and 2013 in the College of Dentistry, King Saud University; the premier dental school in Saudi Arabia. Ethical approval for the study was obtained from the Institutional Review Board of the institution (College of Dentistry Research Center, FR 0181). All cases with incomplete data on age, sex, and location of the lesion were excluded (n=54 cases). We included 231 (of 285) soft-tissue biopsies of patients aged 60years and above with complete demographic data, in addition to their histological slides from the archives, in the analysis. The pathology reports of all cases, including the accompanying hematoxylin-eosin-stained slides, those with special stains and/or immunohistochemical stains were re-evaluated by the two authors (who are practicing oral pathologists) to ensure that the previous diagnoses were correct. When found to be inaccurate, particularly based on current knowledge, new diagnoses were assigned. Descriptive and qualitative analyses of the data were then made using the IBM SPSS version 20 software. Data are presented as frequencies and percentages. Associations between important variables (mainly age and sex in relation to lesions) were tested by Pearson’s Chi-square test or Fisher’s exact test where necessary. A P value <0.05 was considered statistically significant.

br Discussion In Taiwan there

In Taiwan, there are relatively few patients with pediatric OSA (under 12 years of age) who are also obese. Moreover, obese pediatric patients with OSA usually suffer from the severe type of OSA, who, thus, would not be suitable candidates for passive MFT using this oral appliance.
As the intergroup comparison shows, the preterm group has significantly lower weight, height, BMI, and growth rate than their full-term peers, pikfyve inhibitor mirroring findings of previous studies. Preterm children often have a higher percentage of REM (as shown at the baseline), but, after the treatment, the percentage of REM decreased in both groups. After the treatment, sleep latency also increased in both groups, especially in the preterm group. This may be attributable to the smaller mouth and higher sensitivity to oral appliances of preterm children.
Second, the study period is relatively short. According to the study of Guimaraes, MFT for as short as 3 months could still yield a significant improvement in adult OSA patients. Despite only 6 months of wearing the oral appliance nightly by the participants in our study, we saw significant improvements such as decreases in the AHI, AHI related to REM sleep, HI, percentage of wake after sleep onset, and mean pikfyve inhibitor rate. We will continue this cohort study to observe the long-term effect of passive MFT using this oral appliance as well as whether the therapeutic effect remains after the use of the oral appliance is stopped.
Third, there is no control group in the study, for example, a group without using the oral device or a group with active MFT. This oral device is composed of a tongue training target set on mandibular advancement. Efforts were made to rule out the effect of the usual MAD, i.e., a device without the rolling bead. The amount of mandibular advancement associated with the wearing of the device was 50% of the maximum mandibular advancement. Despite these efforts, it remains possible that some of the positive gains could partially be related to the effect of a plain MAD. With the current product design, a control group using MADs without the tongue bead will be needed to further delineate the contributors to these positive gains.

Varicocele (VC) is a vascular lesion characterized by dilatation and tortuosity of the spermatic veins. It is commonly found in adolescents and young adults and has an incidence of 4.4–22.6% in the general male population. It is well known that VC is implicated as a cause of infertility in a high percentage of men. It has been shown that 21–41% of men with primary infertility and 75–81% of those with secondary infertility suffer VC. Although the physiopathology of VC and its relationship with male infertility have been discussed for the last 50 years, the exact mechanism by which the VC affects spermatogenesis is still unclear.
Spermatogenesis is a complex process and involves cell division, differentiation, and is controlled by hormones and other regulatory factors. In the testis, stem cell factor (SCF) is produced by Sertoli cells, and interacts with its tyrosine kinase receptor, c-KIT, on spermatogonia (Spg) A1–A4, spermatocytes, and round spermatids, as well as Leydig cells. SCF binds the c-KIT receptor, and as a result, tyrosine kinase activity is induced. During testicular development, the interaction of SCF and c-KIT plays an essential role in primordial germ cell migration and survival, and in spermatogonial adhesion and proliferation. Based on the researches on the role of SCF and c-KIT in normal and impaired spermatogenesis, it has been concluded that both factors can be critical for reproductive events and are important for germ cell development and fertility. Natural mutations in c-KIT and/or SCF are known to arrest primordial germ cell proliferation and differentiation leading to infertility in mice. It has been shown that the functions of Spg are affected by SCF signaling through knocking down c-KIT expression.

br Materials and methods br Acknowledgments This work is

Materials and methods

This work is supported by a Grant from NIH/NIAID (R21AI116180) to J.Z.. J.Z. is supported in part by the UR CFAR Grant from NIH (P30AI078498) and the UR Center for Integrative Bioinformatics and Experimental Mathematics (CIBEM) pilot Grant. We also thank Stephen Dewhurst (URMC), Stephen Elledge (Harvard), and Abraham Brass (UMass) for helpful discussions.

Monkeypox pikfyve inhibitor (MPXV) is the most severe poxvirus infection of humans, excluding variola virus, and has been designated as a Select Agent by the United States government because of the potential to exploit MPXV for bioterrorism. MPXV primarily infects rodents in Africa but can be transmitted to other animals as well as humans. Human monkeypox clinically resembles smallpox except for lower mortality and fewer human-to-human transmissions (McCollum and Damon, 2014; Parker et al., 2007). A virulent strain of MPXV is prevalent in the rain forests of central Africa, particularly in the Democratic Republic of the Congo, whereas a milder strain is present in West Africa. The latter was imported to the United States with infected dormice, rope squirrels and giant pouched rats in 2003 and spread to closely housed North American prairie dogs and ultimately to humans, resulting in 47 laboratory confirmed and additional clinically diagnosed human cases (Hutson et al., 2007; Reynolds and Damon, 2012). The ability to infect prairie dogs and other wild rodents and the occurrence of sporadic human MPXV infections in countries neighboring the Democratic Republic of the Congo, contribute to concerns that monkeypox may be an emerging disease.
Several small animal models including the American black-tailed prairie dog, the thirteen-lined ground squirrel, and the African dormouse have been used for studies of MPXV pathogenicity, antivirals and vaccines (Hutson and Damon, 2010; Parker and Buller, 2013). However, pikfyve inhibitor except for the African dormouse these animals are not readily raised in captivity and there are no commercial sources of the latter. Moreover, immunological reagents are not available for these rodents. Although the commonly used classical inbred mouse strains are relatively resistant to MPXV, a few wild-derived inbred strains are susceptible (Americo et al., 2010) and one of these, the CAST/EiJ mouse, has been further studied (Americo et al., 2014; Earl et al., 2012). The susceptibility to MPXV varied by age and route and was greater by the intraperitoneal route (LD50=14PFU) compared to the intranasal route (LD50=680PFU) for 6-week old female mice (Americo et al., 2010). Scarification and footpad inoculation only caused local lesions. The low interferon γ response of CAST mice to infection with MPXV and the protection afforded by exogenous interferon γ may be clues to the nature of their susceptibility (Earl et al., 2012). Moreover, the sensitivity of CAST mice extends to other orthopoxviruses including vaccinia virus and cowpox virus (Americo et al., 2014). The primary purpose of the present study was to analyze the susceptibility to MPXV of mouse strains that showed less severe symptoms than CAST mice in the initial screen and to gain insight into the genetics of resistance by cross breeding sensitive and resistant strains.


Common classical inbred mice have mosaic genomes derived predominantly from the Western European Mus musculus domesticus with additional sequences mainly from the Japanese M. m. molossinus and exhibit limited diversity (Takada et al., 2013). Our previous (Americo et al., 2010) and present data demonstrating the relative resistance to MPXV infection displayed by more than 30 classical inbred strains, likely represent conserved genetic sequences. The two most sensitive classical inbred strains of 32 tested are NZW/Lac and C58, although all survived doses up to 106PFU. In contrast, we found that genetically diverse wild-derived strains exhibit a broad range of susceptibilities to MPXV. CAST and CASA are the most sensitive with LD50 of less than 103, MOLF has intermediate sensitivity with a LD50 of less than 104 and PERA has a LD50 of greater than 105. CAST and CASA are species of M.m. castaneus that were derived from a small population of founder mice originally trapped in a grain storage facility in Thailand (JAX® NOTES Issue 456, Winter 1994). However, as CAST and CASA mice were inbred separately in different laboratories, the founder mice may also have been susceptible to MPXV. MOLF is an inbred species of M. m. molossinus that was derived from mice trapped in Japan and PERA is an inbred species of M. m. domesticus trapped in Peru. Not all wild-derived mice are highly susceptible to MPXV; however, since in our initial screen we found that SPRET/EiJ and CZECHII/EIJ lost no weight at all after infection with 2×104PFU and PWK/PhJ lost less than 8%.