Does milk cause constipation? a crossover dietary trial

The aims of this study were to: (1) determine whether replacement of cow’s milk protein with soy resolves Chronic Functional Constipation (CFC); and (2) investigate the effects of cow’s milk β casein A1 and cow’s milk β casein A2 on CFC. Children diagnosed with CFC were recruited to one of two crossover trials: Trial 1 compared the effects of cow’s milk and soy milk; Trial 2 compared the effects of cow’s milk β casein A1 and cow’s milk β casein A2. Resolution of constipation was defined as greater than eight bowel motions during a two week intervention. Thirteen children (18 to 144 months) participated in Trial 1 (6 boys, 7 girls). Nine participants who completed the soy epoch all experienced resolution (p < 0.05). Thirty-nine children (21 to 144 months) participated in Trial 2 (25 boys, 14 girls). Resolution of constipation was highest during the washout epoch, 81%; followed by cow’s milk β casein A2, 79%; and cow’s milk β casein A1, 57%; however, the proportions did not differ statistically. The results of Trial 1 demonstrate an association between CFC and cow’s milk consumption but Trial 2 failed to show an effect from type of casein. Some other component in cow’s milk common to both A1 and A2 milk may be causing a problem in these susceptible children

Sentry bioconvertible inferior vena cava filter: Study of stages of incorporation in an experimental ovine model

The Sentry inferior vena cava (IVC) filter is designed to provide temporary protection from pulmonary embolism (PE) and then bioconvert to become incorporated in the vessel wall, leaving a patent IVC lumen. Objective. To evaluate the performance and stages of incorporation of the Sentry IVC filter in an ovine model. Methods. Twenty-four bioconvertible devices and 1 control retrievable filter were implanted in the infrarenal IVC of 25 sheep, with extensive daily monitoring and intensive imaging. Vessels and devices were analyzed at early (≤98 days, n = 10) and late (180 ± 30 days, n = 14 study devices, 1 control) termination and necropsy time-points. Results. Deployment success was 100% with all devices confirmed in filtering configuration, there were no filter-related complications, and bioconversion was 100% at termination with vessels widely patent. By 98 days for all early-incorporation analysis animals, the stabilizing cylindrical part of the Sentry frame was incorporated in the vessel wall, and the filter arms were retracted. By 180 days for all late-incorporation analysis animals, the filter arms as well as frames were stably incorporated. Conclusions. Through 180 days, there were no filter-related complications, and the study devices were all bioconverted and stably incorporated, leaving all IVCs patent

A Multidisciplinary Approach to Resolving the End-Guadalupian Extinction

The transition from the middle to late Permian (Guadalupian–Lopingian) is claimed to record one or more extinction events that rival the ‘Big Five’ in terms of depletion of biological diversity and reorganization of ecosystem structure. Yet many questions remain as to whether the events recorded in separate regions were synchronous, causally related, or were of a magnitude rivaling other major crises in Earth\u27s history. In this paper, we survey some major unresolved issues related to the Guadalupian–Lopingian transition and offer a multidisciplinary approach to advance understanding of this under-appreciated biotic crisis by utilizing records in Southern Hemisphere high-palaeolatitude settings. We focus on the Bowen-Gunnedah-Sydney Basin System (BGSBS) as a prime site for analyses of biotic and physical environmental change at high palaeolatitudes in the middle and terminal Capitanian. Preliminary data suggest the likely position of the mid-Capitanian event is recorded in regressive deposits at the base of the Tomago Coal Measures (northern Sydney Basin) and around the contact between the Broughton Formation and the disconformably overlying Pheasants Nest Formation (southern Sydney Basin). Initial data suggest that the end-Capitanian event roughly correlates to the transgressive “Kulnura Marine Tongue” in the middle of the Tomago Coal Measures (northern Sydney Basin) and strata bearing dispersed, ice-rafted gravel in the Erins Vale Formation (southern Sydney Basin). Preliminary observations suggest that few plant genera or species disappeared in the transition from the Guadalupian to Lopingian, and the latter interval saw an increase in floristic diversity

The Atacama Cosmology Telescope: Two-Season ACTPol Spectra and Parameters

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg$^2$ of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with Planck and WMAP data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the LCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. Adding the new data to planck temperature data tightens the limits on damping tail parameters, for example reducing the joint uncertainty on the number of neutrino species and the primordial helium fraction by 20%.Comment: 23 pages, 25 figure

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

Antibody attributes that predict the neutralization and effector function of polyclonal responses to SARS-CoV-2

BACKGROUND: While antibodies can provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. METHODS: We employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. RESULTS: To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. CONCLUSIONS: Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions

EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Aneurysmal subarachnoid hemorrhage (SAH) may be complicated by delayed cerebral ischemia, which is a major cause of unfavorable clinical outcome and death in SAH-patients. Delayed cerebral ischemia is presumably related to the development of vasospasm triggered by the presence of blood in the basal cisterns. To date, oral application of the calcium antagonist nimodipine is the only prophylactic treatment for vasospasm recognized under international guidelines.</p> <p>In retrospective trials lumbar drainage of cerebrospinal fluid has been shown to be a safe and feasible measure to remove the blood from the basal cisterns and decrease the incidence of delayed cerebral ischemia and vasospasm in the respective study populations. However, the efficacy of lumbar drainage has not been evaluated prospectively in a randomized controlled trial yet.</p> <p>Methods/Design</p> <p>This is a protocol for a 2-arm randomized controlled trial to compare an intervention group receiving early continuous lumbar CSF-drainage and standard neurointensive care to a control group receiving standard neurointensive care only. Adults suffering from a first aneurysmal subarachnoid hemorrhage whose aneurysm has been secured by means of coiling or clipping are eligible for trial participation. The effect of early CSF drainage (starting < 72 h after securing the aneurysm) will be measured in the following ways: the primary endpoint will be disability after 6 months, assessed by a blinded investigator during a personal visit or standardized telephone interview using the modified Rankin Scale. Secondary endpoints include mortality after 6 months, angiographic vasospasm, transcranial Doppler sonography (TCD) mean flow velocity in both middle cerebral arteries and rate of shunt insertion at 6 months after hospital discharge.</p> <p>Discussion</p> <p>Here, we present the study design of a multicenter prospective randomized controlled trial to investigate whether early application of a lumbar drainage improves clinical outcome after aneurysmal subarachnoid hemorrhage.</p> <p>Trial registration</p> <p>www.clinicaltrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01258257">NCT01258257</a></p

Mouse CD94/NKG2A Is a Natural Killer Cell Receptor for the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule Qa-1b

Natural killer (NK) cells preferentially lyse targets that express reduced levels of major histocompatibility complex (MHC) class I proteins. To date, the only known mouse NK receptors for MHC class I belong to the Ly49 family of C-type lectin homodimers. Here, we report the cloning of mouse NKG2A, and demonstrate it forms an additional and distinct class I receptor, a CD94/NKG2A heterodimer. Using soluble tetramers of the nonclassical class I molecule Qa-1b, we provide direct evidence that CD94/NKG2A recognizes Qa-1b. We further demonstrate that NK recognition of Qa-1b results in the inhibition of target cell lysis. Inhibition appears to depend on the presence of Qdm, a Qa-1b-binding peptide derived from the signal sequences of some classical class I molecules. Mouse NKG2A maps adjacent to CD94 in the heart of the NK complex on mouse chromosome six, one of a small cluster of NKG2-like genes. Our findings suggest that mouse NK cells, like their human counterparts, use multiple mechanisms to survey class I expression on target cells