Effects of a tongue training program in Parkinson's disease: Analysis of electrical activity and strength of suprahyoid muscles

ObjectiveTo assess the electrical activity of the suprahyoid muscle and the tongue pressure in a two-wing program of tongue strengthening in individuals with Parkinson's disease (PD).MethodsA pre-post-detraining design study included sixty PD patients assigned to two groups randomly. The experimental group (EG) performed tongue isometric pressure exercises using the Iowa Oral Performance Instrument with an increasing scheme of 5% load weekly and traditional tongue therapy for 8 weeks. The control group (CG) performed only traditional therapy. The electrical activity of suprahyoids was measured using surface electromyography (sEMG) during tongue-to-palate pressure. Four selected domains of the Swallowing Quality of Life Questionnaire (SWAL-QOL) mostly related to tongue strength were considered.ResultsThe experimental group showed increased sEMG values of suprahyoid muscles reaching statistically significant difference at the fourth week of tongue training, while the control did it at the eighth week. Experimental group showed significant improvements in tongue strength (d = 2.128; p = 0.000). Only controls showed detraining effect. Statistically significant difference within groups were found in one and three dimensions of the SWAL-QOL in the CG and EG, respectively.ConclusionAnalysis of electrical activity on suprahyoids muscles provided a better understanding of the changes underlying the outcomes of tongue strength gains obtained through a combined tongue strengthening exercises protocol in PD. Such protocol led not only to increased tongue strength but also to a better perceived swallowing function in PD subjects.     

Differential hygienic behavior of Apis cerana F. and Apis mellifera L. to Sacbrood virus infection

Beekeeping with Apis cerana of Korean apiculture is facing with serious colony collapse caused by invasive Sacbrood virus (SBV) disease. This fatal brood disease was the main reason of more than 90% colony lost in Korea leading almost the extinct crisis. Sacbrood virus can infect either larvae or adult honeybees, with a higher sensibility of larvae to the infection. Since SBV has spread to all over the country, efforts have been made to treat and prevent this devastating disease although no effective results have so far been obtained. Several studies have demonstrated that Apis mellifera bee colonies that express an efficient hygienic behavior exhibit a higher resistance to the brood disease. In this study we demonstrated that the differences of hygienic behavior between A. cerana and A. mellifera. A. cerana more efficiently removed the pin-killed brood than A. mellifera. On the other hand, A. mellifera more efficiently removed SBV-infected larvae and SBV-dead brood than A. cerana. However, it remains unclear whether the advantage of hygienic bee could have efficacy against Sacbrood disease on A. cerana colonies.     

Why is sterility virulence most common in sexually transmitted infections? Examining the role of epidemiology

Sterility virulence, or the reduction in host fecundity due to infection, occurs in many host–pathogen systems. Notably, sterility virulence is more common for sexually transmitted infections (STIs) than for directly transmitted pathogens, while other forms of virulence tend to be limited in STIs. This has led to the suggestion that sterility virulence may have an adaptive explanation. By focusing upon finite population models, we show that the observed patterns of sterility virulence can be explained by consideration of the epidemiological differences between STIs and directly transmitted pathogens. In particular, when pathogen transmission is predominantly density invariant (as for STIs), and mortality is density dependent, sterility virulence can be favored by demographic stochasticity, whereas if pathogen transmission is predominantly density dependent, as is common for most directly transmitted pathogens, sterility virulence is disfavored. We show these conclusions can hold even if there is a weak selective advantage to sterilizing.     

Evidence for transmission of the zoonotic apicomplexan parasite Babesia duncani by the tick Dermacentor albipictus

Babesiosis is a potentially fatal tick-borne zoonotic disease caused by a species complex of blood parasites that can infect a variety of vertebrates, particularly dogs, cattle, and humans. In the United States, human babesiosis is caused by two distinct parasites, Babesia microti and Babesia duncani. The enzootic cycle of B. microti, endemic in the northeastern and upper midwestern regions, has been well characterised. In the western United States, however, the natural reservoir host and tick vector have not been identified for B. duncani, greatly impeding efforts to understand and manage this zoonotic disease. Two and a half decades after B. duncani was first described in a human patient in Washington State, USA, we provide evidence that the enzootic tick vector is the winter tick, Dermacentor albipictus, and the reservoir host is likely the mule deer, Odocoileus hemionus. The broad, overlapping ranges of these two species covers a large portion of far-western North America, and is consistent with confirmed cases of B. duncani in the far-western United States.     

Magnetic resonance imaging based modeling of microvascular perfusion in patients with peripheral artery disease

Peripheral artery disease (PAD) is associated with an increased risk of adverse cardiovascular events, impaired lower extremity blood flow and microvascular perfusion abnormalities in the calf muscles which can be determined with contrast-enhanced magnetic resonance imaging (CE-MRI). We developed a computational model of the microvascular perfusion in the calf muscles. We included 20 patients (10 PAD, 10 controls) and utilized the geometry, mean signal intensity and arterial input functions from CE-MRI calf muscle perfusion scans. The model included the microvascular pressure (p_v), outflow filtration coefficient (OFC), transfer rate constant (k^t), porosity (φ), and the interstitial permeability (K_tissue). Parameters were fitted and the simulations were compared across PAD patients and controls. Intra-observer reproducibility of the simulated mean signal intensities was excellent (intraclass correlation coefficients >0.995). k^t and K_tissue were higher in PAD patients compared with controls (4.72 interquartile range (IQR) 3.33, 5.56 vs. 2.47 IQR 2.10, 2.85; p = 0.003; and 3.68 IQR 3.18, 4.41 vs. 1.81 IQR 1.81, 1.81; p < 0.001). Conversely, porosity (φ) was lower in PAD patients compared with controls (0.52 IQR 0.49, 0.54 vs. 0.61 IQR 0.58, 0.64; p = 0.016). Porosity (φ) was correlated with the ankle brachial index (r = 0.64, p = 0.011). The proposed computational microvascular model is robust and reproducible, and essential model parameters differ significantly between PAD patients and controls.     

Gait stride-to-stride variability and foot clearance pattern analysis in Idiopathic Parkinson’s Disease and Vascular Parkinsonism

The literature on gait analysis in Vascular Parkinsonism (VaP), addressing issues such as variability, foot clearance patterns, and the effect of levodopa, is scarce. This study investigates whether spatiotemporal, foot clearance and stride-to-stride variability analysis can discriminate VaP, and responsiveness to levodopa.Fifteen healthy subjects, 15 Idiopathic Parkinson's Disease (IPD) patients and 15 VaP patients, were assessed in two phases: before (Off-state), and one hour after (On-state) the acute administration of a suprathreshold (1.5 times the usual) levodopa dose. Participants were asked to walk a 30-meter continuous course at a self-selected walking speed while wearing foot-worn inertial sensors. For each gait variable, mean, coefficient of variation (CV), and standard deviations SD1 and SD2 obtained by Poincaré analysis were calculated. General linear models (GLMs) were used to identify group differences. Patients were subject to neuropsychological evaluation (MoCA test) and Brain MRI.VaP patients presented lower mean stride velocity, stride length, lift-off and strike angle, and height of maximum toe (later swing) (p < .05), and higher %gait cycle in double support, with only the latter unresponsive to levodopa. VaP patients also presented higher CV, significantly reduced after levodopa. Yet, all VaP versus IPD differences lost significance when accounting for mean stride length as a covariate.In conclusion, VaP patients presented a unique gait with reduced degrees of foot clearance, probably correlated to vascular lesioning in dopaminergic/non-dopaminergic cortical and subcortical non-dopaminergic networks, still amenable to benefit from levodopa. The dependency of gait and foot clearance and variability deficits from stride length deserves future clarification.     

A study on the protective effects of CpG oligodeoxynucleotide-induced mucosal immunity against lung injury in a mouse acute respiratory distress syndrome model

This study aims to determine the feasibility of using oligodeoxynucleotides with unmethylated cytosine-guanine dinucleotide sequences (CpG ODN) as an immunity protection strategy for a mouse model of acute respiratory distress syndrome (ARDS). This is a prospective laboratory animal investigation. Twenty-week-old BALB/c mice in Animal research laboratory were randomized into groups. An ARDS model was induced in mice using lipopolysaccharides (LPSs). CpG ODN was intranasally and transrectally immunized before or after the 3rd and 7th days of establishing the ARDS model. Mice were euthanized on Day 7 after the second immunization. Then, retroorbital bleeding was carried out and the chest was rapidly opened to collect the trachea and tissues from both lungs for testing. CpG ODN significantly improved the pathologic impairment in mice lung, especially after the intranasal administration of 50 μg. This resulted in the least severe lung tissue injury. Furthermore, interleukin-6 (IL-6) and IL-8 concentrations were lower, which was second to mice treated with the rectal administration of 20 µg CpG ODN. In contrast, the nasal and rectal administration of CpG ODN in BALB/c mice before LPS immunization did not appear to exhibit any significant protective effects. The intranasal administration of CpG ODN may be a potential treatment approach to ARDS. More studies are needed to further determine the protective mechanism of CpG ODN.     

Heme oxygenase-1 reduces the sensitivity to imatinib through nonselective activation of histone deacetylases in chronic myeloid leukemia

Resistance towards imatinib (IM) remains troublesome in treating many chronic myeloid leukemia (CML) patients. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism in association with cell resistance to apoptosis. Our previous studies have shown that overexpression of HO-1 resulted in resistance development to IM in CML cells, while the mechanism remains unclear. In the current study, the IM-resistant CML cells K562R indicated upregulation of some of the histone deacetylases (HDACs) compared with K562 cells. Therefore, we herein postulated HO-1 was associated with HDACs. Silencing HO-1 expression in K562R cells inhibited the expression of some HDACs, and the sensitivity to IM was increased. K562 cells transfected with HO-1 resisted IM and underwent obvious some HDACs. These findings related to the inhibitory effects of high HO-1 expression on the reactive oxygen species (ROS) signaling pathway that negatively regulated HDACs. Increased expression of HO-1 activated HDACs by inhibiting ROS production. In summary, HO-1, which is involved in the development of drug resistance in CML cells by regulating the expression of HDACs, is probably a novel target for improving CML therapy.     

Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

Autophagy is a preserved cytoplasmic self-degradation process and endorses recycling of intracellular constituents into bioenergetics for the controlling of cellular homeostasis. Functional autophagy process is essential in eliminating cytoplasmic waste components and helps in the recycling of some of its constituents. Studies have revealed that neurodegenerative disorders may be caused by mutations in autophagy-related genes and alterations of autophagic flux. Alzheimer’s disease (AD) is an irrevocable deleterious neurodegenerative disorder characterized by the formation of senile plaques and neurofibrillary tangles (NFTs) in the hippocampus and cortex. In the central nervous system of healthy people, there is no accretion of amyloid β (Aβ) peptides due to the balance between generation and degradation of Aβ. However, for AD patients, the generation of Aβ peptides is higher than lysis that causes accretion of Aβ. Likewise, the maturation of autophagolysosomes and inhibition of their retrograde transport creates favorable conditions for Aβ accumulation. Furthermore, increasing mammalian target of rapamycin (mTOR) signaling raises tau levels as well as phosphorylation. Alteration of mTOR activity occurs in the early stage of AD. In addition, copious evidence links autophagic/lysosomal dysfunction in AD. Compromised mitophagy is also accountable for dysfunctional mitochondria that raises Alzheimer’s pathology. Therefore, autophagic dysfunction might lead to the deposit of atypical proteins in the AD brain and manipulation of autophagy could be considered as an emerging therapeutic target. This review highlights the critical linkage of autophagy in the pathogenesis of AD, and avows a new insight to search for therapeutic target for blocking Alzheimer’s pathogenesis.     

EA15, MIR22, LINC00472 as diagnostic markers for diabetic kidney disease

This study aimed to investigate the molecular mechanisms of diabetic kidney disease (DKD) and to explore new potential therapeutic strategies and biomarkers for DKD. First we analyzed the differentially expressed changes between patients with DKD and the control group using the chip data in Gene Expression Omnibus (GEO) database. Then the gene chip was subjected to be annotated again, so as to screen long noncoding RNAs (lncRNAs) and study expression differences of these lncRNAs in DKD and controlled samples. At last, the function of the differential lncRNAs was analyzed. A total of 252 lncRNAs were identified, and 14 were differentially expressed. In addition, there were 1,629 differentially expressed messenger RNAs (mRNAs) genes, and proliferation and apoptosis adapter protein 15 (PEA15), MIR22, and long intergenic nonprotein coding RNA 472 ( LINC00472) were significantly differentially expressed in DKD samples. Through functional analysis of the encoding genes coexpressed by the three lncRNAs, we found these genes were mainly enriched in type 1 diabetes and autoimmune thyroid disease pathways, whereas in Gene Ontology (GO) function classification, they were also mainly enriched in the immune response, type I interferon signaling pathways, interferon-γ mediated signaling pathways, and so forth. To summary, we identified EA15, MIR22, and LINC00472 may serve as the potential diagnostic markers of DKD.