Bifidobacteria Abundance-Featured Gut Microbiota Compositional Change in Patients with Behcet’s Disease

Gut microbiota compositional alteration may have an association with immune dysfunction in patients with Behcet’s disease (BD). We conducted a fecal metagenomic analysis of BD patients. We analyzed fecal microbiota obtained from 12 patients with BD and 12 normal individuals by sequencing of 16S ribosomal RNA gene. We compared the relative abundance of bacterial taxa. Direct comparison of the relative abundance of bacterial taxa demonstrated that the genera Bifidobacterium and Eggerthella increased significantly and the genera Megamonas and Prevotella decreased significantly in BD patients compared with normal individuals. A linear discriminant analysis of bacterial taxa showed that the phylum Actinobacteria, including Bifidobacterium, and the family Lactobacillaceae exhibited larger positive effect sizes than other bacteria in patients with BD. The phylum Firmicutes and the class Clostridia had large effect sizes in normal individuals. There was no significant difference in annotated species numbers (as numbers of operational taxonomic unit; OTU) and bacterial diversity of each sample (alpha diversity) between BD patients and normal individuals. We next assigned each sample to a position using three axes by principal coordinates analysis of the OTU table. The two groups had a significant distance as beta diversity in the 3-axis space. Fecal sIgA concentrations increased significantly in BD patients but did not correlate with any bacterial taxonomic abundance. These data suggest that the compositional changes of gut microbes may be one type of dysbiosis (unfavorable microbiota alteration) in patients with BD. The dysbiosis may have an association with the pathophysiology of BD.     

Proteomic Analysis of Differentially Expressed Proteins between Stenotic and Normal Colon Segment Tissues Derived from Patients with Hirschsprung’s Disease

Hirschsprung’s disease (HSCR) is the most common identifiable developmental disorder of the enteric nervous system. The present study was designed to analyze the differential proteomic patterns in stenotic colon segment tissues from patients with HSCR. We analyzed 20 paired stenotic and normal colon segment tissues from patients with HSCR, and identified 13 proteins from stenotic segment tissues peptide fingerprint mapping and SELDI MS that were separated using 2-DE. The protein levels of four selected proteins (α-actinin-4, ACTN4; myosin regulatory light chain interacting protein, MYLIP; fatty acid binding protein 7, FABP7; bone morphogenetic protein receptor type 1A, BMPR1A) were further validated by Western blot analysis. This study, investigating for the first time proteomic changes in stenotic colon segment tissues from patients with HSCR, provides potential markers or promising new candidate actors for the pathogenesis of HSCR.     

Characterization of Interstitial Cajal Progenitors Cells and Their Changes in Hirschsprung’s Disease

Interstitial cells of Cajal (ICC) are critical to gastrointestinal motility. The phenotypes of ICC progenitors have been observed in the mouse gut, but whether they exist in the human colon and what abnormal changes in their quantity and ultrastructure are present in Hirschsprung’s disease (HSCR) colon remains uncertain. In this study, we collected the surgical resection of colons, both proximal and narrow segments, from HSCR patients and normal controls. First, we identified the progenitor of ICC in normal adult colon using immunofluorescent localization techniques with laser confocal microscopy. Next, the progenitors were sorted to observe their morphology. We further applied flow cytometry to examine the content of ICC progenitors in these fresh samples. The ultrastructural changes in the narrow and proximal parts of the HSCR colon were observed using transmission electron microscopy (TEM) and were compared with the normal adult colon. The presumed early progenitor (c-Kit^lowCD34⁺Igf1r⁺) and committed progenitor (c-Kit⁺CD34⁺Igf1r⁺) of ICC exist in adult normal colon as well as in the narrow and proximal parts of the HSCR colon. However, the proportions of mature, early and committed progenitors of ICC were dramatically reduced in the narrow segment of the HSCR colon. The proportions of mature and committed progenitors of ICC in the proximal segment of the HSCR colon were lower than in the adult normal colon. Ultrastructurally, ICC, enteric nerves, and smooth muscle in the narrow segment of the HSCR colon showed severe injury, including swollen vacuola or ted mitochondria, disappearance of mitochondrial cristae, dilated rough endoplasmic reticulum, vesiculation and degranulation, and disappearance of the caveolae on the ICC membrane surface. The contents of ICC and its progenitors in the narrow part of the HSCR colon were significantly decreased than those of adult colon, which may be associated with HSCR pathogenesis.     

Neuronal Activity of the Subthalamic Nucleus in Patients with Parkinson’s Disease

The discharge activity of 637 neurons of the human subthalamic nucleus (STN), which were extracellularly recorded during twelve stereotactic surgeries in patients with Parkinson’s disease, has been analyzed. On the basis of the parameters of interspike intervals (ISIs), we have distinguished three major patterns of spontaneous neuronal activity: bursting neurons, regular tonic and irregular tonic neurons. Parametric analysis has enabled us to determine the values of basic parameters in the activity of these three distinguished types of neurons. It has been shown that the representativeness and the activity parameters of three different patterns change in the dorsoventral direction of the STN from the motor to the associative regions. The results will allow researchers to perform targeted search of pathological neuronal activity patterns associated with the motor symptoms of Parkinsonism.     

Characterization of and Functional Antigen Presentation by Central Nervous System Mononuclear Cells from Mice Infected with Theiler’s Murine Encephalomyelitis Virus

We examined the phenotype and function of cells infiltrating the central nervous system (CNS) of mice persistently infected with Theiler’s murine encephalomyelitis virus (TMEV) for evidence that viral antigens are presented to T cells within the CNS. Expression of major histocompatibility complex (MHC) class II in the spinal cords of mice infected with TMEV was found predominantly on macrophages in demyelinating lesions. The distribution of I-A^s staining overlapped that of the macrophage marker sialoadhesin in frozen sections and coincided with that of another macrophage/microglial cell marker, F4/80, by flow cytometry. In contrast, astrocytes, identified by staining with glial fibrillary acidic protein, rarely expressed detectable MHC class II, although fibrillary gliosis associated with the CNS damage was clearly seen. The costimulatory molecules B7-1 and B7-2 were expressed on the surface of most MHC class II-positive cells in the CNS, at levels exceeding those found in the spleens of the infected mice. Immunohistochemistry revealed that B7-1 and B7-2 colocalized on large F4/80⁺ macrophages/microglia in the spinal cord lesions. In contrast, CD4⁺ T cells in the lesions expressed mainly B7-2, which was found primarily on blastoid CD4⁺ T cells located toward the periphery of the lesions. Most interestingly, plastic-adherent cells freshly isolated from the spinal cords of TMEV-infected mice were able to process and present TMEV and horse myoglobin to antigen-specific T-cell lines. Furthermore, these cells were able to activate a TMEV epitope-specific T-cell line in the absence of added antigen, providing conclusive evidence for the endogenous processing and presentation of virus epitopes within the CNS of persistently infected SJL/J mice.Theiler’s murine encephalomyelitis virus (TMEV) is a picornavirus that induces a lifelong persistent central nervous system (CNS) infection leading to a chronic CNS demyelinating disease when inoculated intracerebrally into susceptible strains of mice. Infected mice develop progressive symptoms of gait disturbance, spastic hind limb paralysis, and urinary incontinence (39), histologically related to perivascular and parenchymal mononuclear cell infiltration and demyelination of white matter tracts within the spinal cord (8, 9, 38). Several lines of evidence have demonstrated that demyelination is immunologically mediated. These include the ability of nonspecific immunosuppression with cyclophosphamide (37), antithymocyte serum (36), and anti-CD4 or anti-major histocompatibility complex (MHC) class II monoclonal antibodies (MAbs) (14, 16, 63) to inhibit or prevent disease and the ability of TMEV-specific tolerance to prevent induction of disease (28). In the highly susceptible SJL/J mouse strain, current evidence indicates that the myelin damage is initiated by TMEV-specific CD4⁺ T cells targeting virus antigen (16, 28, 45, 46, 54), while the chronic stage of the disease also involves CD4⁺ myelin epitope-specific T cells primed via epitope spreading (48). Thus, the immune response itself may be deleterious to CNS function, as exemplified in humans by multiple sclerosis (MS), for which TMEV infection serves as a model.The identity of the cells responsible for initiating and sustaining immune responses in the CNS remains controversial. The CNS lacks normal lymphatic circulation and tissue and is shielded from the systemic circulation by a specialized continuous vascular endothelium (6). There are specialized cells within the CNS with the potential to present antigens to T cells. In vitro, astrocytes (11, 59) and microglia (3, 13), particularly when treated with gamma interferon (IFN-γ), are capable of expressing MHC class II and presenting antigens to T cells. However, studies such as these have relied on the ability to isolate and continuously culture cells from neonatal or embryonic brain and have assumed that such cells are representative of the adult populations in vivo. Antigen presentation by neonatal cells in long-term culture may not faithfully reproduce the in vivo state in adult animals, as the ability of microglia directly isolated from adult rats to present myelin basic protein (MBP) to T-cell lines in vitro was found to differ from that of neonatally derived microglia (12). In addition, studies using allogeneic bone marrow chimeras between strains of mice or rats have generally supported the idea that cells of hematopoietic origin, i.e., microglia and macrophages, are the principal antigen-presenting cells (APCs) in the CNS active during the initiation of experimental autoimmune encephalomyelitis (EAE) (20, 22, 50). Although they are much more abundant than microglia, astrocytes are less potent when inducing EAE in chimeras (50).The role of antigen presentation in the CNS during TMEV-induced demyelination has not been addressed directly. We previously showed that a relatively large fraction of the CD4⁺, but not CD8⁺, T cells isolated from the spinal cords of TMEV-infected mice expressed high-affinity interleukin-2 (IL-2) receptor (IL-2R), a marker of recent T-cell activation. In addition, TMEV-specific CD4⁺ T cells could be demonstrated in the spinal cord infiltrates of TMEV-infected mice (54). This finding raises the possibility that T cells are locally activated within the target tissue and participate directly in the pathogenesis of disease. Macrophages (5, 41, 56), astrocytes (7, 56), and oligodendroglia (55, 56) in TMEV-infected mice contain virus and conceivably could present viral antigens to pathogenic CD4⁺ T cells within the CNS. Isolated microglia (34) and astrocytes (17) have been shown to support persistent viral infection in vitro, and astrocytes derived from neonatal mice have been shown to present TMEV to T cells in vitro (2). To examine whether CNS cells present viral antigens and participate in the pathogenesis of TMEV-induced demyelination, the expression of MHC class II and B7 costimulatory molecules was examined in detail. Based on our previous results showing that a large proportion of CD4⁺ T cells isolated from the CNS of TMEV-infected mice bear markers of recent activation, we also asked if mononuclear cells isolated from the CNS of TMEV-infected mice were capable of presenting viral antigens leading to the functional activation of Th1 lines in vitro.     

Transplantation of Neuronal Precursors Derived from Induced Pluripotent Stem Cells into the Striatum of Rats with the Toxin-induced Model of Huntington’s Disease

Introduction. Huntington’s disease (HD) is a severe neurodegenerative disorder characterized by choreic hyperkinesis, cognitive decline, behavioral disorders, and progressive neuronal death, mostly in the striatum. Since HD is a fatal disorder, searching for efficient treatment methods, including those based on cell replacement therapy, is quite relevant. The experimental models of HD are used increasingly often. The objective of the study was to assess effectiveness and safety of transplantation of neuronal precursors differentiated from induced pluripotent stem cells (iPSCs) from a healthy donor into the striatum of rats with 3-NPAinduced HD model. Materials and methods. We studied the influence of neurotransplantation on the behavioral effects in rats with HD model induced by intrastriatal injection of 3-nitropropiotic acid (3-NPA). In the study group of animals (n = 11), human neuronal precursors derived from iPSCs of a healthy volunteer were transplanted into the caudate nuclei (5 × 10⁵ per 5 μL of normal saline solution bilaterally); the control group of animals (n = 10) received normal saline solution. The animals were tested using the ANY-maze video tracking system; the parameters of the open-field test and the conditioned avoidance response test were evaluated. Results. An analysis of behavioral effects after transplantation demonstrated that introduction of neuronal iPSC derivatives into the caudate nuclei of rats with induced HD model was accompanied by recovery of locomotor activity of the animals (horizontal and vertical), as opposed to the control group. It was found when testing the reproducibility of the conditioned avoidance responses that the conditioned avoidance responses in control animals were weakened, whereas intrastriatal transplantation of neurons abruptly increased the latency of moving into the dark compartment of the chamber in the conditioned avoidance response test. Conclusions. The pilot experiment using the HD model showed that neurotransplantation using iPSC derivatives recovers the reduced locomotor activity in rats and improves memory trace keeping, which contributes to correction of locomotor and cognitive disorders induced by 3-NPA neurotoxin.     

Targeting Glial Cells to Elucidate the Pathogenesis of Huntington’s Disease

Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by expended CAG repeats in the Huntingtin (Htt) gene. The resultant mutant Htt (mHtt) forms aggregates in neurons and causes neuronal dysfunctions. The major characteristic of HD is the selective loss of neurons in the striatum and cortex, which leads to movement disorders, dementia, and eventual death. Expression of mHtt was also found in non-neuronal cells in the brain, suggesting non-cell-autonomous neurotoxicity in HD. As was documented in many different neurodegenerative disorders, elevated inflammatory responses are also reported in HD. To date, effective treatments for this devastating disease remain to be developed. This review focuses on the importance of glial cells and inflammation in HD pathogenesis. Potential anti-inflammatory interventions for HD are also discussed.     

Effects of Vitamin C on Fibroblasts from Sporadic Alzheimer’s Disease Patients

Several therapies for Alzheimer’s Disease (AD) are currently under investigation. Some studies have reported that concentration of vitamins in biological fluids are lower in AD patients compared to control subjects and clinical evidence has shown the therapeutic potential of vitamin C and E in delaying AD progression. However, the molecular mechanism(s) that are engaged upon their administration in the APP metabolism in vitro or in vivo still need clarifying. Here, we investigate the effects of vitamin C supplementation, at physiological concentration, in skin fibroblasts obtained from SAD and FAD patients. This study shows that SAD patients’ fibroblasts exhibited the exclusive appearance of C-terminal fragments, derived from APP processing, without giving rise to the β-amyloid peptide, other than corresponding decreased levels of lysosomal enzymes, such as β-hexosaminidase, α-mannosidase and cathepsins B, L, and D. Special issue article in honor of Anna Maria Giuffrida-Stella.     

Isolation of Double Negative αβ T Cells from the Kidney

There is currently no standard protocol for the isolation of DN T cells from the non-lymphoid tissues despite their increasingly reported involvement in various immune responses. DN T cells are a unique immune cell type that has been implicated in regulating immune and autoimmune responses and tolerance to allotransplants^1-6. DN T cells are, however, rare in peripheral blood and secondary lymphoid organs (spleen and lymph nodes), but are major residents of the normal kidney. Very little is known about their pathophysiologic function⁷ due to their paucity in the periphery. We recently described a comprehensive phenotypic and functional analysis of this population in the kidney⁸ in steady state and during ischemia reperfusion injury. Analysis of DN T cell function will be greatly enhanced by developing a protocol for their isolation from the kidney.Here, we describe a novel protocol that allows isolation of highly pure ab CD4+ CD8+ T cells and DN T cells from the murine kidney. Briefly, we digest kidney tissue using collagenase and isolate kidney mononuclear cells (KMNC) by density gradient. This is followed by two steps to enrich hematopoietic T cells from 3% to 70% from KMNC. The first step consists of a positive selection of hematopoietic cells using a CD45+ isolation kit. In the second step, DN T cells are negatively isolated by removal of non-desired cells using CD4, CD8, and MHC class II monoclonal antibodies and CD1d α-galcer tetramer. This strategy leads to a population of more than 90% pure DN T cells. Surface staining with the above mentioned antibodies followed by FACs analysis is used to confirm purity.     

Is Gut Dysbiosis an Epicenter of Parkinson’s Disease?

Once recognized as one of the most esoteric diseases of the central nervous system, Parkinson’s disease (PD) is now deemed to be a chronic illness contributed by the central, autonomic and enteric nervous systems. Most likely, an accumulation of α-synuclein in the central and enteric nervous systems is the key that supports this viewpoint. Constipation, one of the non-motor hallmarks in roughly two-third of PD patients, is regulated by the composition of gut bacteria, which is assumed to set off the enteric α-synuclein accrual. Vagus nerve is suggested to direct the signal for α-synuclein over-expression and accumulation to the brain. While trillions of microorganisms reside in the intestinal tract, only one third of the proportion inhabits evenly in all individuals. Existence of an impaired gut-microbe-brain axis consonant with dysbiosis could be an epicenter of this inexplicable disorder. Any alteration in the structure and function of the gastrointestinal tract owing to exposure of endogenous or exogenous chemicals or toxicants could lead to dysbiosis. However, inconsistency in the symptoms even after exposure to same chemical or toxicant in PD patients emphatically creates a conundrum. While the level of a few specific neurotransmitters and metabolites is influenced by microbes, implication of dysbiosis is still debatable. Nevertheless, the scientific literature is overflowing with the remarkable observations supporting the role of dysbiosis in PD. Lack of specificity to differentially diagnose PD with non-PD or PD-plus syndrome, to identify highly precise drug targets and to develop therapeutic stratagems to encounter the disease on the basis of this approach, causes us to be open-minded about the dysbiosis theory. The article reviews the facts supporting gut dysbiosis as the foremost trigger for PD onset along with disagreements.

     

Susceptibility-Weighted Imaging Manifestations in the Brain of Wilson’s Disease Patients

Purpose

It is well known that patients with Wilson’s disease (WD) suffer copper metabolism disorder. However, recent studies point to an additional iron metabolism disorder in WD patients. The purpose of our study was to examine susceptibility-weighted imaging (SWI) manifestations of WD in the brains of WD patients.

Methods

A total of 33 patients with WD and 18 normal controls underwent conventional MRI (Magnetic resonance imaging) and SWI. The phase values were measured on SWI-filtered phase images of the bilateral head of the caudate nuclei, globus pallidus, putamen, thalamus, substantia nigra, and red nucleus. Student’s t-tests were used to compare the phase values between WD groups and normal controls.

Results

The mean phase values for the bilateral head of the caudate nuclei, globus pallidus, putamen, thalamus, substantia nigra, and red nucleus were significantly lower than those in the control group (P < 0.001), and bilateral putamen was most strongly affected.

Conclusions

There is paramagnetic mineralization deposition in brain gray nuclei of WD patients and SWI is an effective method to evaluate these structures.     

Inflammation and Programmed Cell Death in Alzheimer’s Disease: Comparison of the Central Nervous System and Peripheral Blood

Although the central nervous system (CNS) has been defined as a privileged site in Alzheimer’s disease (AD), periphery can be more than simply witness of events leading to neurodegeneration. The CNS and peripheral blood can mutually communicate through cells and factors trafficking from the circulation into the brain and vice versa. A number of articles have reviewed inflammatory profiles and programmed cell death (PCD) in AD, separately in the CNS and at the peripheral level. This review does not provide an exhaustive account of what has been published on inflammation and PCD in AD. Rather, the aim of this review is to focus on possible linkages between the central and the peripheral compartments during AD progression, by critically analyzing, in a comparative manner, phenomena occurring in the CNS as well as the peripheral blood. In fact, growing evidence suggests that CNS and peripheral inflammation might present common features in the disease. Microarrays and metabolomics revealed that dysfunction of the glycolytic and oxidative pathways is similar in the brain and in the periphery. Moreover, dysregulated autophagosome/lysosomal molecular machinery, both at the CNS and the peripheral level, in AD-related cell damage, has been observed. Possible implications of these observations have been discussed.     

Oxidative Stress in Skin Fibroblasts Cultures of Patients with Huntington’s Disease

Oxidative stress and mitochondrial dysfunction should play a role in the neurodegeneration in Huntington’s disease (HD). The most consistent finding is decreased activity of the mitochondrial complexes II/III and IV of the respiratory chain in the striatum. We assessed enzymatic activities of respiratory chain enzymes and other enzymes involved in oxidative processes in skin fibroblasts cultures of patients with HD. We studied respiratory chain enzyme activities, activities of total, Cu/Zn- and Mn-superoxide-dismutase, glutathione-peroxidase (GPx) and catalase, and coenzyme Q₁₀ (CoQ₁₀) levels in skin fibroblasts cultures from 13 HD patients and 13 age- and sex-matched healthy controls. When compared with controls, HD patients showed significantly lower specific activities for catalase corrected by protein concentrations (P < 0.01). Oxidized, reduced and total CoQ₁₀ levels (both corrected by citrate synthase (CS) and protein concentrations), and activities of total, Cu/Zn- and Mn-superoxide-dismutase, and gluthatione-peroxidase, did not differ significantly between HD-patients and control groups. Values for enzyme activities in the HD group did not correlate with age at onset and of the disease and with the CAG triplet repeats. The primary finding of this study was the decreased activity of catalase in HD patients, suggesting a possible contribution of catalase, but not of other enzymes related with oxidative stress, to the pathogenesis of this disease.     

Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn’s Disease Patients and Unaffected First-Degree Relatives

Crohn’s disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn’s disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn’s disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH₂-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn’s disease.     

Endothelial Progenitor Cells and Cardiovascular Events in Patients with Chronic Kidney Disease – a Prospective Follow-Up Study

Background

Endothelial progenitor cells (EPCs) mediate vascular repair and regeneration. Their number in peripheral blood is related to cardiovascular events in individuals with normal renal function.

Methods

We evaluated the association between functionally active EPCs (cell culture) and traditional cardiovascular risk factors in 265 patients with chronic kidney disease stage V receiving hemodialysis therapy. Thereafter, we prospectively assessed cardiovascular events, e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aorto-coronary bypass, stroke and angiographically verified stenosis of peripheral arteries, and cardiovascular death in this cohort.

Results

In our patients EPCs were related only to age (r = 0.154; p = 0.01). During a median follow-up period of 36 months 109 (41%) patients experienced a cardiovascular event. In a multiple Cox regression analysis, we identified EPCs (p = 0.03) and patient age (p = 0.01) as the only independent variables associated with incident cardiovascular events. Moreover, a total of 70 patients died during follow-up, 45 of those due to cardiovascular causes. Log rank test confirmed statistical significance for EPCs concerning incident cardiovascular events (p = 0.02).

Conclusions

We found a significant association between the number of functionally active EPCs and cardiovascular events in patients with chronic kidney disease. Thus, defective vascular repair and regeneration may be responsible, at least in part, for the enormous cardiovascular morbidity in this population.     

Mycobacterium avium Subspecies Paratuberculosis in the Inflamed Gut Tissues of Patients with Crohn’s Disease in China and its Potential Relationship to the Consumption of Cow’s Milk: A Preliminary Study

Summary Mycobacterium avium subspecies paratuberculosis infection in domestic livestock is widespread in many countries throughout the world. Studies in Europe and the USA show that M. avium subspecies paratuberculosis can be cultured from retail pasteurized cow’s milk and that these organisms are being transmitted to humans by this route. Most people with chronic inflammation of the intestine of the Crohn’s disease type are infected with these chronic enteric pathogens. The production and consumption of cow’s milk has increased in China and so also has the incidence of Crohn’s disease. The present preliminary investigation was carried out to determine whether M. avium subspecies paratuberculosis is present in the intestinal tissues of Chinese patients with Crohn’s disease who have never left China. Archival paraffin-embedded surgical pathology blocks from patients having surgery for Crohn’s disease (CD) or for cancer (nIBD) in China were studied. M. avium subspecies paratuberculosis was detected by nested IS900 PCR with Southern blotting and amplicon sequencing. The intestinal tissues of 9 of 13 (69.2%) CD patients and 2 of 14 (14.3%) nIBD patients were IS900 PCR positive (P = 0.0063; odds ratio = 13.5). These initial studies suggest that people in China are exposed to M. avium subspecies paratuberculosis and that as in other countries, the infection is significantly associated with Crohn’s disease. M. avium subspecies paratuberculosis in dairy herds and retail milk in China needs to be investigated.     

Atrophic Patterns of the Frontal-Subcortical Circuits in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

Atrophy of the cortical thickness and gray matter volume are regarded as sensitive markers for the early clinical diagnosis of Alzheimer’s disease (AD). This study aimed to investigate differences in atrophy patterns in the frontal-subcortical circuits between MCI and AD, assess whether these differences were essential for the pathologic basis of cognitive impairment. A total of 131 individuals were recruited, including 45 with cognitively normal controls (CN), 46 with MCI, and 40 with AD. FreeSurfer software was used to perform volumetric measurements of the frontal-subcortical circuits from 3.0T magnetic resonance (MR) scans. Data revealed that both MCI and AD subjects had a thinner cortex in the left caudal middle frontal gyrus and the left lateral orbitofrontal gyrus compared with CN individuals. The left lateral orbitofrontal gyrus was also thinner in AD compared with MCI patients. There were no statistically significant differences in the cortical mean curvature among the three groups. Both MCI and AD subjects exhibited smaller bilateral hippocampus volumes compared with CN individuals. The volumes of the bilateral hippocampus and the right putamen were also smaller in AD compared with MCI patients. Logistic regression analyses revealed that the left lateral orbitofrontal gyrus and bilateral hippocampus were risk factors for cognitive impairment. These current results suggest that atrophy was heterogeneous in subregions of the frontal-subcortical circuits in MCI and AD patients. Among these subregions, the reduced thickness of the left lateral orbitofrontal and the smaller volume of the bilateral hippocampus seemed to be markers for predicting cognitive impairment.