Serum immunoglobulin G, M and A response to Cryptosporidium parvum in Cryptosporidium-HIV co-infected patients

<p>Abstract</p> <p>Background</p> <p><it>Cryptosporidium parvum</it>, the protozoan parasite, causes a significant enteric disease in immunocompromised hosts such as HIV patients. The present study was aimed to compare serum IgG, IgM and IgA responses to crude soluble antigen of <it>C. parvum </it>in HIV seropositive and seronegative patients co-infected with <it>Cryptosporidium </it>and to correlate the responses with symptomatology.</p> <p>Methods</p> <p><it>Cryptosporidium parvum </it>specific serum antibody (IgG, IgM and IgA) responses were assessed by ELISA in 11 HIV seropositive <it>Cryptosporidium </it>positive (Group I), 20 HIV seropositive <it>Cryptosporidium </it>negative (Group II), 10 HIV seronegative <it>Cryptosporidium </it>positive (Group III), 20 HIV seronegative <it>Cryptosporidium </it>negative healthy individuals (Group IV) and 25 patients with other parasitic diseases (Group V).</p> <p>Results</p> <p>A positive IgG and IgA antibody response was observed in significantly higher number of <it>Cryptosporidium </it>infected individuals (Gp I and III) compared to <it>Cryptosporidium </it>un-infected individuals (Gp II, IV and V) irrespective of HIV/immune status. Sensitivity of IgG ELISA in our study was found to be higher as compared to IgM and IgA ELISA. The number of patients with positive IgG, IgM and IgA response was not significantly different in HIV seropositive <it>Cryptosporidium </it>positive patients with diarrhoea when compared to patients without diarrhoea and in patients with CD4 counts <200 when compared to patients with CD4 counts >200 cells/μl.</p> <p>Conclusion</p> <p>The study showed specific serum IgG and IgA production in patients infected with <it>Cryptosporidium</it>, both HIV seropositive and seronegative as compared to uninfected subjects suggesting induction of <it>Cryptosporidium </it>specific humoral immune response in infected subjects. However, there was no difference in number of patients with positive response in HIV seropositive or seronegative groups indicating that HIV status may not be playing significant role in modulation of <it>Cryptosporidium </it>specific antibody responses. The number of patients with positive IgG, IgM and IgA response was not significantly different in patients with or without history of diarrhoea thereby indicating that <it>Cryptosporidium </it>specific antibody responses may not be necessarily associated with protection from symptomatology.</p

Cerebellum Abnormalities in Idiopathic Generalized Epilepsy with Generalized Tonic-Clonic Seizures Revealed by Diffusion Tensor Imaging

Although there is increasing evidence suggesting that there may be subtle abnormalities in idiopathic generalized epilepsy (IGE) patients using modern neuroimaging techniques, most of these previous studies focused on the brain grey matter, leaving the underlying white matter abnormalities in IGE largely unknown, which baffles the treatment as well as the understanding of IGE. In this work, we adopted multiple methods from different levels based on diffusion tensor imaging (DTI) to analyze the white matter abnormalities in 14 young male IGE patients with generalized tonic-clonic seizures (GTCS) only, comparing with 29 age-matched male healthy controls. First, we performed a voxel-based analysis (VBA) of the fractional anisotropy (FA) images derived from DTI. Second, we used a tract-based spatial statistics (TBSS) method to explore the alterations within the white matter skeleton of the patients. Third, we adopted region-of-interest (ROI) analyses based on the findings of VBA and TBSS to further confirm abnormal brain regions in the patients. At last, considering the convergent evidences we found by VBA, TBSS and ROI analyses, a subsequent probabilistic fiber tractography study was performed to investigate the abnormal white matter connectivity in the patients. Significantly decreased FA values were consistently observed in the cerebellum of patients, providing fresh evidence and new clues for the important role of cerebellum in IGE with GTCS

The Effects of Sleep Hypoxia on Coagulant Factors and Hepatic Inflammation in Emphysematous Rats

OBJECTIVES: To develop a sleep hypoxia (SH) in emphysema (SHE) rat model and to explore whether SHE results in more severe hepatic inflammation than emphysema alone and whether the inflammation changes levels of coagulant/anticoagulant factors synthesized in the liver. METHODS: Seventy-five rats were put into 5 groups: SH control (SHCtrl), treated with sham smoke exposure (16 weeks) and SH exposure (12.5% O(2), 3 h/d, latter 8 weeks); emphysema control (ECtrl), smoke exposure and sham SH exposure (21% O(2)); short SHE (SHEShort), smoke exposure and short SH exposure (1.5 h/d); mild SHE (SHEMild), smoke exposure and mild SH exposure (15% O(2)); standard SHE (SHEStand), smoke exposure and SH exposure. Therefore, ECtrl, SHEShort, SHEMild and SHEStand group were among emphysematous groups. Arterial blood gas (ABG) data was obtained during preliminary tests. After exposure, hepatic inflammation (interleukin -6 [IL-6] mRNA and protein, tumor necrosis factor α [TNFα] mRNA and protein) and liver coagulant/anticoagulant factors (antithrombin [AT], fibrinogen [FIB] and Factor VIII [F VIII]) were evaluated. SPSS 11.5 software was used for statistical analysis. RESULTS: Characteristics of emphysema were obvious in emphysematous groups and ABGs reached SH criteria on hypoxia exposure. Hepatic inflammation parameters and coagulant factors are the lowest in SHCtrl and the highest in SHEStand while AT is the highest in SHCtrl and the lowest in SHEStand. Inflammatory cytokines of liver correlate well with coagulant factors positively and with AT negatively. CONCLUSIONS: When SH is combined with emphysema, hepatic inflammation and coagulability enhance each other synergistically and produce a more significant liver-derivative inflammatory and prothrombotic status

Cortical Thinning in Patients with Recent Onset Post-Traumatic Stress Disorder after a Single Prolonged Trauma Exposure

Most of magnetic resonance imaging (MRI) studies about post-traumatic stress disorder (PTSD) focused primarily on measuring of small brain structure volume or regional brain volume changes. There were rare reports investigating cortical thickness alterations in recent onset PTSD. Recent advances in computational analysis made it possible to measure cortical thickness in a fully automatic way, along with voxel-based morphometry (VBM) that enables an exploration of global structural changes throughout the brain by applying statistical parametric mapping (SPM) to high-resolution MRI. In this paper, Laplacian method was utilized to estimate cortical thickness after automatic segmentation of gray matter from MR images under SPM. Then thickness maps were analyzed by SPM8. Comparison between 10 survivors from a mining disaster with recent onset PTSD and 10 survivors without PTSD from the same trauma indicates cortical thinning in the left parietal lobe, right inferior frontal gyrus, and right parahippocampal gyrus. The regional cortical thickness of the right inferior frontal gyrus showed a significant negative correlation with the CAPS score in the patients with PTSD. Our study suggests that shape-related cortical thickness analysis may be more sensitive than volumetric analysis to subtle alteration at early stage of PTSD

The impact of transposable element activity on therapeutically relevant human stem cells

Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome, and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for the biosafety of stem cells to be used for substitutive and regenerative cell therapiesS.R.H. and P.T.R. are funded by the Government of Spain (MINECO, RYC-2016- 21395 and SAF2015–71589-P [S.R.H.]; PEJ-2014-A-31985 and SAF2015–71589- P [P.T.R.]). GGS is supported by a grant from the Ministry of Health of the Federal Republic of Germany (FKZ2518FSB403)

Sleeping tongue: current perspectives of genioglossus control in healthy individuals and patients with obstructive sleep apnea

Jennifer M Cori,1 Fergal J O&rsquo;Donoghue,1 Amy S Jordan2 1Department of Respiratory and Sleep Medicine, Institute for Breathing and Sleep, Austin Hospital, Heidelberg, VIC, Australia; 2Department of Psychology, Melbourne School of Psychological Sciences, University of Melbourne, Parkville, VIC, Australia Abstract: The focus of this review was on the genioglossus (GG) muscle and its role in maintaining upper airway patency in both healthy individuals and obstructive sleep apnea (OSA) patients. This review provided an overview of GG anatomy and GG control and function during both wakefulness and sleep in healthy individuals and in those with OSA. We reviewed evidence for the role of the GG in OSA pathogenesis and also highlighted abnormalities in GG morphology, responsiveness, tissue movement patterns and neurogenic control that may contribute to or result from OSA. We summarized the different methods for improving GG function and/or activity in OSA and their efficacy. In addition, we discussed the possibility that assessing the synergistic activation of multiple upper airway dilator muscles may provide greater insight into upper airway function and OSA pathogenesis, rather than assessing the GG in isolation. Keywords: pharyngeal dilators, upper airway, airway obstruction, airway collapsibility and slee

Sleeping tongue: current perspectives of genioglossus control in healthy individuals and patients with obstructive sleep apnea

The focus of this review was on the genioglossus (GG) muscle and its role in maintaining upper airway patency in both healthy individuals and obstructive sleep apnea (OSA) patients. This review provided an overview of GG anatomy and GG control and function during both wakefulness and sleep in healthy individuals and in those with OSA. We reviewed evidence for the role of the GG in OSA pathogenesis and also highlighted abnormalities in GG morphology, responsiveness, tissue movement patterns and neurogenic control that may contribute to or result from OSA. We summarized the different methods for improving GG function and/or activity in OSA and their efficacy. In addition, we discussed the possibility that assessing the synergistic activation of multiple upper airway dilator muscles may provide greater insight into upper airway function and OSA pathogenesis, rather than assessing the GG in isolation

The presence of coexisting sleep-disordered breathing among women with hypertensive disorders of pregnancy does not worsen perinatal outcome

OBJECTIVE: To determine whether the presence of co-existing sleep-disordered breathing (SDB) is associated with worse perinatal outcomes among women diagnosed with a hypertensive disorder of pregnancy (HDP), compared with normotensive controls. STUDY DESIGN: Women diagnosed with HDP (gestational hypertension or preeclampsia) and BMI- and gestation-matched controls underwent polysomnography in late pregnancy to determine if they had coexisting SDB. Fetal heart rate (FHR) monitoring accompanied the sleep study, and third trimester fetal growth velocity was assessed using ultrasound. Cord blood was taken at delivery to measure key regulators of fetal growth. RESULTS: SDB was diagnosed in 52.5% of the HDP group (n = 40) and 38.1% of the control group (n = 42); p = .19. FHR decelerations were commonly observed during sleep, but the presence of SDB did not increase this risk in either the HDP or control group (HDP group-SDB = 35.3% vs. No SDB = 40.0%, p = 1.0; control group-SDB = 41.7% vs. No SDB = 25.0%, p = .44), nor did SDB affect the total number of decelerations overnight (HDP group-SDB = 2.7 ± 1.0 vs. No SDB = 2.8 ± 2.1, p = .94; control group-SDB = 2.0 ± 0.8 vs. No SDB = 2.0 ± 0.7, p = 1.0). Fetal growth restriction was the strongest predictor of fetal heart rate events during sleep (aOR 5.31 (95% CI 1.26-22.26), p = .02). The presence of SDB also did not adversely affect fetal growth; in fact among women with HDP, SDB was associated with significantly larger customised birthweight centiles (43.2% ± 38.3 vs. 16.2% ± 27.0, p = .015) and fewer growth restricted babies at birth (30% vs. 68.4%, p = .026) compared to HDP women without SDB. There was no impact of SDB on measures of fetal growth for the control group. Cord blood measures of fetal growth did not show any adverse effect among women with SDB, either in the HDP or control group. CONCLUSION: We did not find that the presence of mild SDB worsened fetal acute or longitudinal outcomes, either among women with HDP or BMI-matched normotensive controls. Unexpectedly, we found the presence of SDB conferred a better prognosis in HDP in terms of fetal growth. The fetus has considerable adaptive capacity to withstand in utero hypoxia, which may explain our mostly negative findings. In addition, SDB in this cohort was mostly mild. It may be that fetal sequelae will only be unmasked in the setting of more severe degrees of SDB and/or underlying placental disease

Sleep-disordered breathing does not impact maternal outcomes in women with hypertensive disorders of pregnancy

OBJECTIVE: Sleep-disordered breathing (SDB) is characterised by intermittent hypoxemia, sympathetic activation and widespread endothelial dysfunction, sharing pathophysiologic features with the hypertensive disorders of pregnancy. We sought to determine whether coexisting SDB would adversely impact the outcomes of women with gestational hypertension (GH) and preeclampsia (PE), and healthy matched controls. STUDY DESIGN: Women diagnosed with GH or PE along with BMI- and gestation-matched normotensive controls underwent polysomnography in late pregnancy to establish the presence or absence of SDB (RDI ≥ 5). Clinical outcomes of hypertensive disease severity were compared between groups, and venous blood samples were taken in the third trimester and at delivery to examine for any impact of SDB on the anti-angiogenic markers of PE. RESULTS: Data was available for 17 women with PE, 24 women with GH and 44 controls. SDB was diagnosed in 41% of the PE group, 63% of the GH group and 39% of the control group. Women with PE and co-existing SDB did not have worse outcomes in terms of gestation at diagnosis of PE (SDB = 29.1 (25.9, 32.1) weeks vs. no SDB = 32.0 (29.0, 33.9), p = n.s.) and days between diagnosis of PE and delivery (SDB = 20.0 (4.0, 35.0) days vs. no SDB = 10.5 (9.0, 14.0), p = n.s.). There were also no differences in severity of hypertension, antihypertensive treatment and biochemical, haematological and anti-angiogenic markers of PE between SDB and no SDB groups. Similar results were observed among women with GH. Healthy control women with SDB were no more likely to develop a hypertensive disorder of pregnancy in the later stages of pregnancy (SDB = 5.9% vs. no SDB = 7.4%, p = n.s.). Increasing the threshold for diagnosis of SDB to RDI ≥ 15 did not unmask a worse prognosis. CONCLUSION: The presence of SDB during pregnancy did not worsen the disease course of GH or PE, and was not associated with high blood pressure or anti-angiogenic markers of hypertensive disease amongst healthy pregnant women. Given the numerous reports of the relationship between SDB and diagnosis of hypertensive disorders of pregnancy, it appears more work is required to distinguish causal, versus confounding, pathways