In the MCD group sleep was possibly compromised for exactly

In the MCD group, sleep was possibly compromised for exactly the same reason (sleep disturbances for nocturnal care due to the use of noninvasive ventilatory support); once, most of the mothers in this group reported the same complaints. However, we could not confirm this information because the evaluation of sleep has a subjective nature, constituting therefore a real study limitation. It is important to note that this condition may persist for years, compromising not only the sleep but also the health and well‐being of these caregiving mothers. Thus, it is fundamental that these caregiving mothers be oriented and followed up by a multidisciplinary team to lead them to a better health condition and maintain the necessary strength to enable them to continuously take good care of their sons, who are totally dependent on them. There are only a few studies with DMD caregivers [40,41] and none examine their sexual function. This study contributes to this field as it provides more significant data in relation to sexuality and quality of sleep of caregiving mothers of sons with DMD.

Conclusions and Future Directions


Bladder cancer (BlCa) is the 4th most common form of cancer in the United States with over 70,000 new p2y receptor cases diagnosed annually [1]. Any malignancy of the pelvis, including BlCa, may lead to sexual dysfunction among men or women, defined as a decrease in sexual desire or variability of the sexual response cycle (i.e., excitement, plateau, orgasm, resolution) due to psychogenic or organic causes. Previous studies have demonstrated that radical cystectomy and urinary diversion, mainstays of surgical management for muscle‐invasive p2y receptor cancer, result in increased incidence of sexual dysfunction [2]. However, non‐muscle‐invasive bladder cancer (NMIBC) accounts for approximately 75% of incident bladder cancers [3]. Sexual dysfunction has not been well‐studied among NMIBC survivors, who frequently undergo surveillance and various intravesical therapies.
Most treatments for BlCa cause substantial side effects that increase as treatments become more invasive and may persist. For example, Bacillus Calmette–Guérin (BCG) treatment may cause pain, dysuria, and urinary frequency [4,5]. Men may also experience erectile difficulties, which may resolve after BCG therapy ends [5]. Since BlCa is primarily a male disease, the limited literature does not include data on sexual dysfunction in women receiving BCG therapy. However, while sexual dysfunction has traditionally been perceived as predominately affecting men, more recent data suggests that a larger percentage of women (43% vs. 31% of men) are affected by sexual dysfunction (e.g., decreased vaginal lubrication, dyspareunia, diminished arousal, or difficulty achieving orgasm) [6].
Transurethral cystoscopy with either rigid or flexible instruments is currently the most common method of monitoring for bladder cancer recurrence and progression. Rigid cystoscopy has been shown to cause transient impairment of sexual function and temporary decrease in libido among sexually‐active patients [7]. Yet, the long‐term effects of repeated surveillance cystoscopy have not been fully evaluated.
Quality of life (QOL) is critical to consider when discussing both the direct effects of cancer and those associated with subsequent treatment. Increasingly, sexual dysfunction has become an important component of QOL measurement, particularly in the evaluation of genitourinary malignancies [8]. Among men, sexual dysfunction, specifically ED, represents a significant cost to the healthcare system [9]. However, existing QOL measures do not fully account for the detrimental psychological effects of sexual dysfunction experienced by men and women (e.g., poor self‐image, diminished self‐esteem, depression mental stress and negative effects on personal relationships). This is particularly true when considering the acute onset of sexual dysfunction secondary to cancer or its treatment. One study using focus groups of men who had undergone definitive therapy for localized prostate cancer showed that physiologic sexual dysfunction impacted the quality of sexual intimacy, everyday interactions with women, sexual imagining and fantasy life, and self‐perceptions of masculinity [10].

Various optimization techniques inspired by biology nature physical

Various optimization techniques inspired by biology, nature, physical based, social based, geography based, musical based, swarm based and many more have been effectively used in various real life and in some other application areas such as science, engineering, biomedical applications, finance, etc. The computational methods such as Evolutionary Optimization (EO) algorithm [4], genetic algorithm [5], Invasive Weed Optimization (IWO) [6], Artificial Immune algorithms (AI) [7–9] are biology based algorithms. Bacterial Foraging algorithm (BFO) [10], Artificial Fish-Swarm algorithm (AFS) [11], Ant Colony algorithm (ACO) [12,13], Saplings Growing Up algorithm (SGU) [14,15], Monkey Search algorithm (MS) [16], Enzyme Algorithm (EA) [17], Firefly Algorithm (FA) [18], Intelligent Water Drop algorithm (IWD) [19], Bee Colony algorithm (BCO) [20,21], Cat Swarm Optimization (CSO) [22,23], Glowworm Swarm Optimization (GSO) [24,25] are some of the important swarm optimization methods. Some physical based algorithms include Electromagnetism-like algorithm (ELA) [26,27], Artificial Physics Optimization algorithm (APO) [28], Big bang–big Crunch optimization (BBCO) [29,30], Charged System Search (CSS) [31,32], Particle Collision Algorithm (PCA) [33], Central Force Optimization (CFO) [34,35], Gravitational Search Algorithm (GSA) [36,37]. The method Teaching learning based optimization (TLBO) [38,39] is based on passing the knowledge within a classroom environment, Harmony search (HS) [40] based on music improvisation of a music player, Shuffled Frog Leaping (SFL) [41] based on communication among frogs, Biogeography-Based Optimization (BBO) [42] based on the principle of immigration and emigration of the p2y receptor from one place to the other, Grenade Explosion Method (GEM) [43] based on principle of explosion of a grenade are some of the meta-heuristics which have proved their efficiency to solve some specific kind of problems.
The remaining part of this paper is organized as follows: Section 2 describes the literature survey of some previous works, Section 3 addresses some basics preliminaries of Pi–Sigma network, chemical reaction optimization, Particle Swarm Optimization and genetic algorithm. In Section 4, the proposed CRO based PSNN has been presented. Experimental setup and result analysis have been presented in Section 5 and 6 respectively. Section 7 is devoted to statistical analysis and cross validation for finding classification accuracy and Section 8 concludes the work with some future directions.

Related work
To circumvent the drawbacks of the earlier developed neural network, some higher order neural networks such as Sigma Pi Neural Network (SPNN) [44], Product Unit Neural Network (PUNN) [45], Higher Order Processing unit neural network (HPUNN) [46] have been developed to perform nonlinear mappings. But unfortunately when the order of network becomes exceptionally high, it affects these networks by the exponential increase of the required higher order terms. In 1992, Shin and Ghosh [1] developed another neural network, which is called the Pi–Sigma neural network which avoids the exponential increase of number of weight vectors along with the processing units. The PSNN uses the product of sum of input components having the linear summation of a single hidden layer and the product of processing units at output layer, instead of sum of product of inputs as other networks. Hussain et al. [47] have proposed a new type of neural network called the recurrent Pi–Sigma neural network (RPSN), used as predictor structure in Differential Pulse Code Modulation systems which utilizes both the temporal dynamics of the image formation process and the multi-linear interactions between the pixels for 1D/2D predictive image coding. Li [48] has suggested a memory based Sigma–Pi–Sigma neural network for excellent learning convergence along with reducing the memory size and overcoming the possible extensive memory requirement problem. Weber and Wermter [49] have presented a sigma-pi network trained with an online learning algorithm for solving the frame of reference transformation problem. For financial time series prediction a novel application of Ridge polynomial network formed by adding different degrees of Pi–Sigma neural networks has been suggested by Ghazali et al. [50] which is able to find an appropriate input output mapping of various chaotic financial time series data with a good performance in learning speed and generalization capability. Kang et al. [51] have proposed an online gradient algorithm for Pi–Sigma neural networks with stochastic inputs, which not only helps to improve the computational efficiency but also to jump off from local minima. Xiu and Xia [52] have developed a switch reluctance motor based on Pi–Sigma neural network and the tested results demonstrate high accuracy, strong ability of generalization, and fast computational speed of the model. Nie and Deng [53] realized that hybrid genetic algorithm can search out the global optimum which is faster than genetic algorithm and their proposed hybrid genetic algorithm trained Pi–Sigma network was used to resolve the function optimization problem. Song et al. [54] have proposed a new visual cryptography scheme for general access structures using Pi–Sigma neural networks to infuse a new activity in visual cryptography researching.

Immunohistochemical staining of ilea tissue

Immunohistochemical staining of ilea tissue sections from E. maxima APU1-infected chickens revealed E. maxima developmental stages at 24 and 48h post-infection (Fig. 5). Similar to previous observations (Riley and Fernando, 1988), early developmental stages of E. maxima were present in both the lamnia propria and crypts of the intestinal villi at both timepoints (Fig. 5A–D). Very faint staining of intracellular stages was observed at later timepoints (72–120h, data not shown). Expression of an immunoreactive protein during early stages of development may explain in part the protective role IMP1 plays in acquired resistance to E. maxima since natural immunity is believed to be directed at early developmental stages (Jeffers and Long, 1985; Jenkins et al., 1993, 1997).

Conflict of interest


Trypanosoma evansi, the causative agent of surra, infects different domestic and wild animals and has a wide geographical distribution. It is transmitted by different genera of hematophagous insects and in Latin America also by vampire bats (Hoare, 1972). Oral transmission to carnivores has been described as well (Raina et al., 1985; Sinha et al., 1971). Among the domestic animals, the most affected are dromedary and Bactrian camels, buffaloes, horses, bovine, small ruminants and dogs. Capybaras are known as wild reservoir in Latin America (Franke et al., 1994). For recent reviews on the distribution and pathology of surra, we refer to Desquesnes et al. (2013).
Parasitological techniques such as Giemsa stained thin smears or thick drops and such as the microhaematocrit centrifugation technique (mHCT), are commonly used for the diagnosis of surra but their sensitivity is low due to the fluctuating and often low parasitaemia, particularly during the chronic stage of the disease (Büscher, 2014). Therefore, serodiagnosis based on the detection of T. evansi specific p2y receptor is recommended by the world organization for animal health (Organization Internationale des Epizooties, OIE) (OIE, 2012). Within the mammalian host, the cell membrane of the trypanosome is covered by a monolayer of variant surface glycoprotein (VSG). This VSG coat is highly immunogenic and induces a strong humoral immune response in the host. As a result, trypanosomes that are recognised by VSG-specific antibodies are distroyed (Horn, 2014; Pays et al., 2004). The VSG conferring the variant antigen type RoTat 1.2 is shared among most T. evansi strains, except in some rare T. evansi strains isolated from dromedary camels in Kenya (Ngaira et al., 2005; Verloo et al., 2001). Several antibody detection tests have been developed that are based on the native VSG RoTat 1.2 including the card agglutination test for trypanosomosis (CATT/T. evansi), enzyme linked immunosorbent assay (ELISA/T. evansi) and immune trypanolysis (TL) (Bajyana Songa and Hamers, 1988; Lejon et al., 2005; Verloo et al., 1998). To avoid the use of laboratory rodents for the production of native VSG RoTat 1.2, the N-terminal domain of VSG RoTat 1.2 has been expressed as recombinant protein in Spodoptera frugiperda insect cells and in Pichia pastoris yeast cells and used as antigen in ELISA and in latex agglutination (Lejon et al., 2005; Rogé et al., 2014; Urakawa et al., 2001). None of the above mentioned serological test formats complies with the ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid, equipment-free and delivered) (Mabey et al., 2004). Therefore, the development of an ASSURED serodiagnostic test for surra remains necessary (Büscher, 2014).
Following the development of the HAT Sero K-SeT for sleeping sickness caused by T. brucei gambiense, we developed a similar test for the serodiagnosis of infection with T. evansi: the Surra Sero K-SeT (Büscher et al., 2013; Büscher et al., 2014). The Surra Sero K-SeT (Coris BioConcept, Gembloux, Belgium) is a lateral flow immunochromatographic test (ICT) for detection of RoTat 1.2-specific antibodies in blood, serum or plasma of any mammalian species. The test uses a fragment of VSG RoTat 1.2, produced as recombinant antigen in P. pastoris (Rogé et al., 2013). In the present study, we report on the diagnostic accuracy of the Surra Sero K-SeT on sera from various domestic animal species from different parts of the world in comparison with CATT/T. evansi and TL as reference test.

In conclusion we verified that

In conclusion, we verified that FAdV-9 ORF1 encodes a functional dUTPase enzyme and characterized its molecular features including transcription and translation patterns and cellular localization. We also demonstrated that, although FAdV-9 dUTPase did not affect virus replication in vitro, it contributed to the up-regulation of type I interferons in vitro. Our data lays the foundation for further exploration on the mechanism of the host immune response against FAdV infection.

Materials and methods

Li Deng was a recipient of a China Scholarship Council PhD fellowship. This work was supported by the Natural Sciences and Engineering Research Council of Canada (Grant # RGPIN 41625), the Canadian Poultry Research Council (CPRC/AAFC Grant # 051801), and the Ontario Ministry of Agriculture, Food and Rural Affairs (OMAFRA Grant # 030019).

Human Cytomegalovirus (HCMV) is a linear double stranded DNA virus ubiquitous in most human populations. HCMV is an opportunistic pathogen that causes medical problems in immunocompromised individuals such as AIDS patients and transplant recipients (Fornara et al., 2011; Shi et al., 2011; Zhang et al., 1995). Some studies also report that HCMV may contribute to certain types of cancers including malignant glioblastomas, prostate carcinomas, and colorectal cancers (Cobbs et al., 2002; Dziurzynski et al., 2012; Harkins et al., 2002; Samanta et al., 2003; Soderberg-Naucler, 2006). Perhaps most problematic is that HCMV is a major cause of congenital birth defects. Approximately 8000 infants are negatively affected each year in the United States. Half of these cases have severe neurological defects at birth that include blindness, deafness, mental retardation, microencephaly, and cerebral calcification. The remaining cases manifest sequelae within 1–2 years after birth (Boppana and Britt, 1996; Boppana et al., 1999; Britt and Alford, 1996; Cinque et al., 1997).
HCMV infection can lead not only to significant negative consequences for its host, but also highly disrupts individual cellular functions including normal cell cycling. Virus-induced re-localization of certain cellular proteins into the viral replication centers (RCs) may, at least in part, be responsible for these disruptions. The RCs are non-membrane bound structures located within the nucleus of infected p2y receptor and are the site of viral DNA replication (de Bruyn Kops and Knipe, 1988; Liptak et al., 1996; Lukonis et al., 1997; Lukonis and Weller, 1996; Quinlan et al., 1984; Rixon et al., 1983; Uprichard and Knipe, 1997). One of the tightly RC-associated cellular proteins is the cell cycle regulatory protein p53 (Fortunato and Spector, 1998). Amongst a myriad of functions, p53 is a specific transcription factor that mediates the cellular damage response. Activation of p53 can lead to either p53-mediated cell cycle arrest (presumably for repair of damaged DNA) or apoptosis (as reviewed in Beckerman and Prives (2010)). These p53-mediated responses do not occur during HCMV infection.
We have previously shown that cellular p2y receptor p53 was required for several viral functions to occur at wild type (wt) levels of activity. Rosenke et al. (2006) reported 21 viral genes have canonical p53 binding sites. p53 was differentially bound at many of these sites during the first 48h post infection (hpi). p53 was found to influence viral gene expression, through either direct or indirect interaction, at early times of infection (Hannemann et al., 2009). Most significantly, the presence of p53 in the infected cell was found to be necessary for wt levels of functional virion secretion (Casavant et al., 2006). Secretion of functional virions was reduced by approximately 25-fold at late times pi in knockout cells completely absent wt p53 (p53KOs).
During the normal course of infection, input pp65, the most abundant tegument protein, transits rapidly to the nucleus via its nuclear localization signal (NLS) (Schmolke et al., 1995). Prior to 48h pi, this protein\’s staining pattern is predominantly nuclear, however, after this timepoint, the vast majority of pp65 is found in the cytoplasm (Sanchez et al., 2000, 2007) and, therefore, has been used as a proxy for virion nuclear maturation (Britt and Vugler, 1987; Casavant et al., 2006; Sanchez et al., 2002). Undoubtedly at least some pp65 protein is still present in the nucleus at late times pi during infection of a wt cell, where it participates in capsid tegumentation. However, in the p53KOs pp65 remained largely confined to the nucleus throughout infection (Casavant et al., 2006). The absence of pp65 from the cytoplasm suggested that nuclear capsids might also be unable to exit the nucleus. Our parallel electron microscopy study found that the absence of p53 disrupted the efficient egress of HCMV capsids from the nucleus (Kuan et al., 2016).

Although most MSC therapies in AKI and CKD rodent models

Although most MSC therapies in AKI and CKD rodent models utilize bmMSCs, more recent studies indicate similar efficacy with aMSCs (Furuichi et al., 2012; Kim et al., 2012). The surface phenotype and immunologic properties of bmMSCs and aMSCs appear to be similar (Strioga et al., 2012), with recent literature even suggesting an added advantage of using aMSCs for immunomodulatory indications (Ivanova-Todorova et al., 2009).
Two different types of MSC products are currently being investigated as a novel therapy for CKD in cats; aMSCs expanded in culture and stromal vascular fraction (SVF) p2y receptor (also known as non-expanded aMSCs). SVF is the initial product of adipose tissue enzymatic digestion and is the type of cellular product produced from point of care tissue processors and by several private stem cell companies. In contrast to aMSC cultures which contain a relatively homogeneous population of activated and proliferating MSCs, the SVF product is a mixture of multiple cell types, primarily cell types such as adipocytes and endothelial cells that do not give rise to MSCs. These are thought to include MSCs as well as a mixture of B and T lymphocytes, endothelial cells, fibroblasts, macrophages, pericytes, and pre-adipocytes (Gimble et al., 2012).
Currently, not enough information is known about SVF to determine if such a product with a mixed cellular composition offers a therapeutic advantage or disadvantage for the intended applications. Culture-expanded MSCs (both bmMSCs and aMSCs) are the type predominantly used in the rodent model literature, however more recent rodent studies have started to explore the therapeutic potential of the SVF cellular product with promising results (Riordan et al., 2009; Yasuda et al., 2012).
Stem cells that are harvested from a patient with the intention of administering them back to that patient are termed autologous MSCs. Stem cells that are harvested from healthy donors for administration to a different, genetically unrelated patient are termed allogeneic MSCs. The relative efficacy of autologous vs. allogeneic cells is an area of controversy. Although allogeneic MSCs traditionally are thought to be immune-privileged and are not expected to incite an immune response, more recent evidence suggests that the terminology ‘immune-evasive’ may be more appropriate as antibody formation against and rejection of allogeneic donor MSCs have been documented (Ankrum et al., 2014). As a result it is argued that autologous MSCs may survive longer in the body in comparison to allogeneic cells, resulting in improved efficacy over the latter (Togel et al., 2009a). Decreased efficacy of allogeneic MSCs in comparison to autologous MSCs has been observed in one acute renal failure rodent study (Togel et al., 2009b). However, allogeneic MSCs have been widely used in experimental stem cell transfer investigations in rodents, as well as clinical trials in humans, with positive results (McTaggart and Atkinson, 2007; Togel et al., 2009b).
The advantages of using allogeneic MSCs include sparing the patient from undergoing the harvest procedure as well as the use of MSCs from young healthy donor animals. Recent studies in humans and rodents support the view that MSCs obtained from young healthy individuals have greater proliferation potential and have greater therapeutic potential than those collected from elderly diseased individuals (Lei et al., 2007; Kretlow et al., 2008; Scruggs et al., 2013; Wang et al., 2013).
Another concern about autologous MSC administration in animals with kidney disease is the growing body of literature supporting the theory that MSCs are adversely affected by uremia (Noh et al., 2012; van Koppen et al., 2012; Idziak et al., 2014; Klinkhammer et al., 2014; Yamada et al., 2014). Recent studies have documented that MSCs obtained from uremic rats have reduced proliferation in culture, caused loss of regenerative potential, premature senescence, decreased capacity to induce angiogenesis, and an altered secretome (Noh et al., 2012; van Koppen et al., 2012; Idziak et al., 2014; Klinkhammer et al., 2014).

br Discussion br Our study determined the


Our study determined the average excursion of the diaphragms during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography (“dynamic X-ray phrenicography”). These findings are important because they provide reference values of diaphragmatic motion during tidal breathing useful for the diagnosis of diseases related to respiratory kinetics. Our study also suggests that dynamic X-ray phrenicography is a useful method for the quantitative evaluation of diaphragmatic motion with a radiation dose comparable to conventional posteroanterior chest radiography (22).

Our study demonstrated that the average excursions of the bilateral p2y receptor during tidal breathing (right: 11.0 mm, 95% CI 10.4 to 11.6 mm; left: 14.9 mm, 95% CI 14.2 to 15.5 mm) were numerically less than those during forced breathing in previous studies using other modalities 2; 7 ;  8. Using fluoroscopy, Alexander reported that the average right excursion was 27.5 mm and the average left excursion was 31.5 mm during forced breathing in the standing position in 127 patients (2). Using ultrasound, Harris et al. reported that the average right diaphragm excursion was 48 mm during forced breathing in the supine position in 53 healthy adults (7). Using MR fluoroscopy, Gierada et al. reported that the average right excursion was 44 mm and the average left excursion was 42 mm during forced breathing in the supine position in 10 healthy volunteers (8). The difference in diaphragmatic excursion during tidal breathing versus forced breathing is unsurprising.

Our study showed that the excursion and peak motion speed of the left diaphragm are significantly greater and faster than those of the right. With regard to the excursion, the results of our study are consistent with those of previous reports using fluoroscopy in a standing position 2 ;  3. However, in the previous studies evaluating diaphragmatic motion in the supine position, the asymmetric diaphragmatic motion was not mentioned 7 ;  8. The asymmetric excursion of the bilateral diaphragm may be more apparent in the standing position, but may not be detectable or may disappear in the supine position. Although we cannot explain the reason for the asymmetry in diaphragmatic motion, we speculate that the presence of the liver may limit the excursion of the right diaphragm. Regarding the motion speed, to the best of our knowledge this study is the first to evaluate it. The faster motion speed of the left diaphragm compared to that of the right diaphragm would be related to the greater excursion of the left diaphragm.

We found that higher BMI and higher tidal volume were independently associated with the increased excursions of the bilateral diaphragm by both univariate and multivariate analyses, although the strength of these associations was weak. We cannot explain the exact reason for the correlation between BMI and the excursion of the diaphragm. However, a previous study showed that BMI is associated with peak oxygen consumption (23), and the increased oxygen consumption in an obese participant may affect diaphragmatic movement. Another possible reason is that lower thoracic compliance due to higher BMI may cause increased movement of the diaphragm for compensation. Regarding the correlation between tidal volume and excursion of the diaphragm, given that diaphragmatic muscle serves as the most important respiratory muscle, the result is to be expected. Considering our results, the excursion evaluated by dynamic X-ray phrenicography could potentially predict tidal volume.

Our study has several limitations. First, we included only 172 volunteers, and additional studies on larger participant populations are required to confirm these preliminary findings. Second, we evaluated only the motion of the highest point of the diaphragms for the sake of simplicity, and three-dimensional motion of the diaphragm could not be completely reflected in our results. However, we believe that this simple method would be practical and more easily applicable in a clinical setting.