Near-infrared spectroscopy and machine learning algorithms for rapid and non-invasive detection of Trichuris.

BACKGROUND: Trichuris trichiura (whipworm) is one of the most prevalent soil transmitted helminths (STH) affecting 604-795 million people worldwide. Diagnostic tools that are affordable and rapid are required for detecting STH. Here, we assessed the performance of the near-infrared spectroscopy (NIRS) technique coupled with machine learning algorithms to detect Trichuris muris in faecal, blood, serum samples and non-invasively through the skin of mice. METHODOLOGY: We orally infected 10 mice with 30 T. muris eggs (low dose group), 10 mice with 200 eggs (high dose group) and 10 mice were used as the control group. Using the NIRS technique, we scanned faecal, serum, whole blood samples and mice non-invasively through their skin over a period of 6 weeks post infection. Using artificial neural networks (ANN) and spectra of faecal, serum, blood and non-invasive scans from one experiment, we developed 4 algorithms to differentiate infected from uninfected mice. These models were validated on mice from a second independent experiment. PRINCIPAL FINDINGS: NIRS and ANN differentiated mice into the three groups as early as 2 weeks post infection regardless of the sample used. These results correlated with those from concomitant serological and parasitological investigations. SIGNIFICANCE: To our knowledge, this is the first study to demonstrate the potential of NIRS as a diagnostic tool for human STH infections. The technique could be further developed for large scale surveillance of soil transmitted helminths in human populations.

TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma.

Intraepithelial lymphocytes (IELs), including αß and γδ T cells (T-IELs), constantly survey and play a critical role in maintaining the gastrointestinal epithelium. We show that cytotoxic molecules important for defense against cancer were highly expressed by T-IELs in the small intestine. In contrast, abundance of colonic T-IELs was dependent on the microbiome and displayed higher expression of TCF-1/TCF7 and a reduced effector and cytotoxic profile, including low expression of granzymes. Targeted deletion of TCF-1 in γδ T-IELs induced a distinct effector profile and reduced colon tumor formation in mice. In addition, TCF-1 expression was significantly reduced in γδ T-IELs present in human colorectal cancers (CRCs) compared with normal healthy colon, which strongly correlated with an enhanced γδ T-IEL effector phenotype and improved patient survival. Our work identifies TCF-1 as a colon-specific T-IEL transcriptional regulator that could inform new immunotherapy strategies to treat CRC.

Executive functioning and the metabolic syndrome: a project FRONTIER study.

Decrements in cognitive functioning have been linked to the metabolic syndrome (MetS), a risk factor for cardiovascular disease defined by the presence of three of the following: elevated blood pressure, increased waist circumference, elevated blood glucose, elevated triglycerides, and low high-density lipoprotein cholesterol. We examined the relationship between four measures of executive functioning (EF) and MetS as diagnosed by National Heart, Lung, and Blood Institute-American Heart Association criteria. MetS was examined in a rural population of 395 persons with a mean age of 61.3 years, 71.4% women, 37.0% Hispanic, 53.7% White non-Hispanic. There was a 61.0% prevalence of MetS. We derived a factor score from the four executive function measures which was used to compare those with and without the syndrome, as well as any additive effects of components of the syndrome. Those with MetS exhibited significantly poorer performance than those without the syndrome. However, there was no additive effect, having more components of the syndrome was not related to lower performance. The presence of MetS was associated with poorer EF in this rural cohort of community dwelling volunteers.

Acute administration of non-classical estrogen receptor agonists attenuates ischemia-induced hippocampal neuron loss in middle-aged female rats.

BACKGROUND: Pretreatment with 17beta-estradiol (E2) is profoundly neuroprotective in young animals subjected to focal and global ischemia. However, whether E2 retains its neuroprotective efficacy in aging animals, especially when administered after brain insult, is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We examined the neuroprotective effects of E2 and two agonists that bind to non-classical estrogen receptors, G1 and STX, when administered after ischemia in middle-aged rats after prolonged ovarian hormone withdrawal. Eight weeks after ovariectomy, middle-aged female rats underwent 10 minutes of global ischemia by four vessel occlusion. Immediately after reperfusion, animals received a single infusion of either E2 (2.25 microg), G1 (50 microg) or STX (50 microg) into the lateral ventricle (ICV) or a single systemic injection of E2 (100 microg/kg). Surviving pyramidal neurons in the hippocampal CA1 were quantified 1 week later. E2 and both agonists that target non-classical estrogen receptors (G1 and STX) administered ICV at the time of reperfusion provided significant levels of neuroprotection, with 55-60% of CA1 neurons surviving vs 15% survival in controls. A single systemic injection of a pharmacological dose of E2 also rescued approximately 50% of CA1 pyramidal neurons destined to die. To determine if E2 and G1 have similar mechanisms of action in hippocampal neurons, we compared the ability of E2 and G1 to modify CA1 pyramidal neuron responses to excitatory inputs from the Schaffer collaterals recorded in hippocampal slices derived from female rats not subjected to global ischemia. E2 and G1 (10 nM) significantly potentiated pyramidal neuron responses to excitatory inputs when applied to hippocampal slices. CONCLUSIONS/SIGNIFICANCE: These findings suggest (1) that middle-aged female rats retain their responsiveness to E2 even after a long period of hormone withdrawal, (2) that non-classical estrogen receptors may mediate the neuroprotective actions of E2 when given after ischemia, and (3) that the neuroprotective efficacy of estrogens may be related to their modulation of synaptic activity in hippocampal slices.

Spontaneous temperature changes in the 2-vessel occlusion model of cerebral ischemia in rats.

Transient global ischemia (ISC) in rats and humans causes selective and delayed neuronal death in the hippocampal CA1 sector. It is clear from rodent studies that hyperthermia aggravates, whereas hypothermia lessens, this injury. In this study we sought to relate core (Tc) and brain (Tb) temperature, measured via telemetry probes, after ISC produced in rats by bilateral common carotid artery occlusion combined with systemic hypotension (2-VO model). We also tested whether spontaneous postischemic temperature fluctuations occurred and whether they were related to cell death as previous studies indicate. We report that Tc and Tb readings are similar and are highly correlated before and after 10 min of 2-VO ISC. In the second experiment, rats were subjected to 8, 9, or 10 min of 2-VO ISC. Despite a range in CA1 injury among these animals, there was no evidence of post-ISC hyperthermia, contrary to earlier work, and neither temperature nor the physiological variables measured during ISC (e.g., glucose) predicted injury. Our findings suggest that, under the present conditions, 2-VO rats do not experience postoperative hyperthermia, which can be adequately measured with Tc telemetry probes.

Failure of estradiol to ameliorate global ischemia-induced CA1 sector injury in middle-aged female gerbils.

Global forebrain ischemia arising from brief occlusion of the carotid arteries in gerbils produces selective hippocampal CA1 neuronal loss. Pre-treatment with 17beta-estradiol ameliorates, in part, ischemia-induced damage in young animals. Because stroke and cardiac arrest are more likely to occur among elderly individuals, neuroprotective studies in older animals have compelling clinical relevance. We investigated whether estradiol would attenuate ischemia-induced hippocampal neuronal injury in middle-aged (12-14 months) male, intact female, ovariectomized (OVX) female and OVX females treated for 14 days with estradiol. Core temperature telemetry probes were also implanted at the time that estradiol was initiated. Ischemia was induced by bilateral occlusion of the common carotid arteries (5 min), during which time skull temperature was maintained under normothermic conditions. Estradiol blocked the modest spontaneous hyperthermia that normally follows ischemia. However, all four groups exhibited substantial neuronal cell loss in the CA1, assessed at 7 after ischemia. These findings indicate that estradiol pre-treatment under conditions that produce neuroprotection in young animals does not protect against ischemia-induced CA1 cell loss in middle-aged female gerbils.