Probiotics: Microbial Therapy for Health Modulation

The human gastrointestinal tract is a complex ecosystem that harbours a rich and diversemicroflora. These microbes live in harmony with the host and exert various beneficial effects onhuman health by their metabolic activities. However, in our modern life style, frequent andindiscriminate use of antibiotics has disturbed this microbial ecosystem, resulting in occurrenceof various bowel diseases. Some live microbial food supplements can re-establish this microbialecosystem. Such a group of microorganisms, which positively influences the intestinal microbiotaby stimulating the growth of beneficial bacteria and suppressing the harmful ones, is collectivelyknown as probiotics. These have been consumed in the form of fermented milk products forcenturies. However, scientific interest in their use for health maintenance and disease preventionhas emerged over the past few years only.Various scientific evidences show that probiotics help to reduce several disorders includingdiarrhea, inflammatory bowel diseases, urinary tract infections, hypertension, allergies, and cancer.Besides, probiotics exert several other benefits also to human beings and animals. Importantissues in the probiotic therapy include selection of appropriate strain, its viability during storage,gut persistence potential and functional properties. Another category involved in gut health isprebiotics. These are non-digestible food ingredients, which beneficially affect the host byselectively stimulating the growth or activity of one or a limited number of beneficial bacteriain the colon. This review paper highlights the major health benefits of probiotic organisms,mechanisms of their action, criteria of selection, enumeration, and safety of their use for humanhealth

Estimating risk of C. difficile transmission from PCR positive but cytotoxin negative cases

Background: The use of molecular methods to diagnose Clostridium difficile infection (CDI) has improved diagnostic yield compared to conventional methods. However, PCR testing can detect colonization and has introduced several practical challenges pertaining to need for treatment and isolation of cases. Methods: For all new cases detected by real-time PCR, concurrent cytotoxin assay was performed and genetic characterization with MLVA (multi-locus variable number tandem repeat analysis) was done to determine relatedness. We used PCR cycle threshold (Ct) of detection as surrogate marker for bacterial burden in stool. Results: Overall, 54 cases of CDI were detected during the study period. 42 were concurrently tested by CYT and characterized by MLVA. MLVA analysis revealed marked genetic diversity with no ongoing outbreaks; four cases were due to NAP1 strain. CYT-/PCR + cases had a higher median Ct value of detection compared to CYT+/PCR + cases (28.2 vs 22.5; p = 0.01). Among 25 strains that were genetically related, 9/11 isolates in this dominant cluster were positive by CYT compared to 4/14 in non-dominant clusters (p = 0.02). Conclusion: CYT-/PCR+ cases contribute to hospital based transmission. However, the risk of transmission of C. difficile from CYT +/PCR+ cases may be higher than those that are CYT-/PCR+. © 2014 Kamboj et al

Mucormycosis infection associated with global COVID-19 pandemic - an institutional histopathological study

Coronavirus disease 2019 (COVID-19) in the recent times have instilled signs of immunosuppression globally which has further precipitated increasing range of opportunistic infections. Mucormycosis is a distressing opportunistic fungal infection with a high incidence and is the third commonest acute invasive infection following candidiasis and aspergillosis. The aim of the present observational study is to delineate the enigmatic histopathological profile between mucormycosis cases seen prior to pandemic (PPM) and pandemic associated mucormycosis (PAM). Tissue archives of 105 histopathologically diagnosed cases of mucormycosis were included and analysed for demographical details and histopathological parameters like fungal load and localization, granuloma formation, necrosis, inflammatory infiltrate and tissue invasion. 0ut of 105 included cases, 11/105 (10.48%) were reported PPM and 94/105 (89.52%) PAM. Among 94 cases of PAM, 51/94 (54%) cases also showed COVID-19 positivity, while 43/94 (46%) did not. Of all the histological variables, increased fungal load and necrosis were observed in PAM relative to PPM cases. The histopathological variables like fungal load, necrosis, granuloma formation and tissue invasion, could help the clinician in assessing the clinical status at the time of tissue diagnosis and improve the treatment accordingly

A process for reducing the licensing burden for new products containing depleted uranium.

This report is intended to provide guidance on the process for petitioning the U.S. Nuclear Regulatory Commission (NRC) to initiate a rulemaking that could reduce the licensing burden for new products containing depleted uranium (DU), which are being investigated by the DU Uses Research and Development (R&D) Program at Oak Ridge National Laboratory (ORNL). The focus is on requirements of the NRC rulemaking process applicable to establishing new exemptions or general licenses for products and devices containing source material. NRC policies and guidance regarding such requirements are described, including a 1965 policy statement on approval of new exemptions for products containing radionuclides (''Federal Register'', Volume 30, page 3462 [30 FR 3462]; March 16, 1965) and Regulatory Guide 6.7, which addresses the contents of environmental reports that support rulemaking petitions seeking exemptions for radionuclide-containing products. Methodologies for calculating radiological and nonradiological impacts on human health (i.e., risks) associated with distributing, using, and disposing of DU-containing products are presented. Also, methodologies for completing assessments of the potential effects of accidents involving new DU-containing products and of product misuse are described. The report recommends that the U.S. Department of Energy formulate a regulatory plan for deployment of DU-containing products in areas that are not already radiologically controlled. Such a plan is needed because deployment of new DU-containing products may be difficult under existing NRC licensing requirements. To provide a basis for the regulatory plan, it is recommended that detailed assessments of the radiological and nonradiological risks of distributing, using, and disposing of DU-containing products be conducted. Such assessments should be initiated as soon as sufficient data are available from the ongoing DU Uses R&D Program at ORNL to support the analyses

All-epitaxial guided-mode resonance mid-wave infrared detectors

We demonstrate all-epitaxial guided-mode resonance mid-wave infrared (MWIR) type-II superlattice nBn photodetectors. Our detectors consist of a high-index absorber/waveguide layer grown above a heavily doped (n þþ), and thus, low-index, semiconductor layer, and below a high-index and wide-bandgap grating-patterned layer. Polarization- and angle-dependent detector response is measured experimentally and simulated numerically, showing strongly enhanced absorption, compared to unpatterned detectors, at wavelengths associated with coupling to guided-mode resonances in our fabricated detectors. The detectors show high operating temperature (T ¼ 200 K) external quantum effi- ciencies over 50% for TE-polarized light with absorber thickness of only 250 nm ( ko=20). We calculate T ¼ 200 K estimated specific detec- tivity for our detectors, on resonance, of 4 10 10 cm Hz1=2 W 1, comparable with state-of-the-art MWIR detectors. The presented results offer an approach to monolithic, all-epitaxial integration of IR detector architectures with resonant optical cavities for enhanced detector response across the mid-wave infrared.This material was based upon work supported by the United States Army under Prime Contract No. W909MY-20-P-0010. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the U.S. Army. The authors gratefully acknowledge support from the National Science Foundation (No. ECCS-1926187 and MRSEC Program No. DMR-1720595). Part of the work was done at the University of Texas Microelectronics Research Center (The Texas Nanofabrication Facility), a member of the National Nanotechnology Coordinated Infrastructure (NNCI), supported by the National Science Foundation (No. ECCS- 2025227).Center for Dynamics and Control of Material

Using Transmissive Photonic Band Edge Shift to Detect Explosives: A Study with 2,4,6-Trinitrotoluene (TNT)

Photonic crystals (PhCs) possess outstanding optical properties that can be exploited for chemical sensing. We utilized a three-dimensional close-packed PhC structure made of functionalized silica nanoparticles. They consist of alternating high and low refractive index regions and have optical properties, such as photonic band structures, that are very sensitive to the change of physical structures. This study used 2,4,6-trinitrotoluene (TNT) to illustrate a detection method based on the transmissive photonic band edge shift (TPBES) due to the binding of TNT with amine anchored on particle surfaces to form Meisenheimer (amine-TNT) complexes. PhCs are exceptionally sensitive to a small change in refractive index caused by surface modification. As a result, they are suitable for sensing specific reactions between an amine and TNT. This method achieved a wide detection range of TNT concentrations from 10$^{-12}$ to 10$^{-4}$ M. 2,4-Dinitrotoluene (DNT) and toluene were used as a control and blank, respectively. Because of gravitational sedimentation, the TNT-functionalized particles were self-assembled in pure ethanol. They were measured by UV–visible transmission spectroscopy. A three-dimensional model to simulate the detection system was built using the particles’ center-to-center distance (a) and effective dielectric constant (ε) as a function of the TNT concentrations. Two sets of simulations were performed: the first set involved a parametric sweep of the center-to-center distance of TNT-functionalized crystals using ε = 2.015. The second set involved a parametric sweep of the dielectric constant with a = 263.1 nm. These perturbations yield a TPBES response that is in agreement with our experimental results

Release process for non-real property containing residual radioactive material

It is DOE`s objective to operate its facilities and to conduct its activities so that radiation exposures to members of the public are maintained within acceptable limits and exposures to residual radioactive materials are controlled. To accomplish this, DOE has adopted Order DOE 5400.51 `Radiation Protection of the Public and the Environment`, and will be promulgating IO CR Part 834 to codify and clarify the requirements of DOE 5400.5. Under both DOE 5400.5 and 10 CR Part 834, radioactively contaminated DOE property is prohibited from release unless specific actions have been completed prior to the release. This paper outlines a ten-step process that, if followed, will assist DOE Operations and contractor personnel in ensuring that the required actions established by Order DOE 5400.5 and 10 CR Part 834 have been appropriately completed prior to the release for reuse or recycle of non-real property (e.g., office furniture, computers, hand tools, machinery, vehicles and scrap metal). Following the process will assist in ensuring that radiological doses to the public from the released materials will meet applicable regulatory standards and be as low as reasonably achievable (ALARA)

Estimating risk of c. difficile transmission from pcr positive but cytotoxin negative cases

Abstract Background: The use of molecular methods to diagnose Clostridium difficile infection (CDI) has improved diagnostic yield compared to conventional methods. However, PCR testing can detect colonization and has introduced several practical challenges pertaining to need for treatment and isolation of cases

Q/R site interactions with the M3 helix in GluK2 kainate receptor channels revealed by thermodynamic mutant cycles

RNA editing at the Q/R site near the apex of the pore loop of AMPA and kainate receptors controls a diverse array of channel properties, including ion selectivity and unitary conductance and susceptibility to inhibition by polyamines and cis-unsaturated fatty acids, as well as subunit assembly into tetramers and regulation by auxiliary subunits. How these different aspects of channel function are all determined by a single amino acid substitution remains poorly understood; however, several lines of evidence suggest that interaction between the pore helix (M2) and adjacent segments of the transmembrane inner (M3) and outer (M1) helices may be involved. In the present study, we have used double mutant cycle analysis to test for energetic coupling between the Q/R site residue and amino acid side chains along the M3 helix. Our results demonstrate interaction with several M3 locations and particularly strong coupling to substitution for L614 at the level of the central cavity. In this location, replacement with smaller side chains completely and selectively reverses the effect of fatty acids on gating of edited channels, converting strong inhibition of wild-type GluK2(R) to nearly 10-fold potentiation of GluK2(R) L614A

Echinocandin Treatment of Pneumocystis Pneumonia in Rodent Models Depletes Cysts Leaving Trophic Burdens That Cannot Transmit the Infection

Fungi in the genus Pneumocystis cause pneumonia (PCP) in hosts with debilitated immune systems and are emerging as co-morbidity factors associated with chronic diseases such as COPD. Limited therapeutic choices and poor understanding of the life cycle are a result of the inability of these fungi to grow outside the mammalian lung. Within the alveolar lumen, Pneumocystis spp., appear to have a bi-phasic life cycle consisting of an asexual phase characterized by binary fission of trophic forms and a sexual cycle resulting in formation of cysts, but the life cycle stage that transmits the infection is not known. The cysts, but not the trophic forms, express β -1,3-D-glucan synthetase and contain abundant β -1,3-D-glucan. Here we show that therapeutic and prophylactic treatment of PCP with echinocandins, compounds which inhibit the synthesis of β -1,3-D-glucan, depleted cysts in rodent models of PCP, while sparing the trophic forms which remained in significant numbers. Survival was enhanced in the echincandin treated mice, likely due to the decreased β -1,3-D-glucan content in the lungs of treated mice and rats which coincided with reductions of cyst numbers, and dramatic remodeling of organism morphology. Strong evidence for the cyst as the agent of transmission was provided by the failure of anidulafungin-treated mice to transmit the infection. We show for the first time that withdrawal of anidulafungin treatment with continued immunosuppression permitted the repopulation of cyst forms. Treatment of PCP with an echinocandin alone will not likely result in eradication of infection and cessation of echinocandin treatment while the patient remains immunosuppressed could result in relapse. Importantly, the echinocandins provide novel and powerful chemical tools to probe the still poorly understood bi-phasic life cycle of this genus of fungal pathogens