Zinc in gut-brain interaction in autism and neurological disorders.

A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life.

Integrated high quality factor lithium niobate microdisk resonators.

Lithium Niobate (LN) is an important nonlinear optical material. Here we demonstrate LN microdisk resonators that feature optical quality factor ~10(5), realized using robust and scalable fabrication techniques, that operate over a wide wavelength range spanning visible and near infrared. Using our resonators, and leveraging LN's large second order optical nonlinearity, we demonstrate on-chip second harmonic generation with a conversion efficiency of 0.109 W(-1).

Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15.

BACKGROUND: Quality of recovery (QoR) after anesthesia is an important measure of the early postoperative health status of patients. The aim was to develop a short-form postoperative QoR score, and test its validity, reliability, responsiveness, and clinical acceptability and feasibility. METHODS: Based on extensive clinical and research experience with the 40-item QoR-40, the strongest psychometrically performing items from each of the five dimensions of the QoR-40 were selected to create a short-form version, the QoR-15. This was then evaluated in 127 adult patients after general anesthesia and surgery. RESULTS: There was good convergent validity between the QoR-15 and a global QoR visual analog scale (r = 0.68, P < 0.0005). Construct validity was supported by a negative correlation with duration of surgery (r = -0.49, P < 0.0005), time spent in the postanesthesia care unit (r = -0.41, P < 0.0005), and duration of hospital stay (r = -0.53, P < 0.0005). There was also excellent internal consistency (0.85), split-half reliability (0.78), and test-retest reliability (ri = 0.99), all P < 0.0005. Responsiveness was excellent with an effect size of 1.35 and a standardized response mean of 1.04. The mean ± SD time to complete the QoR-15 was 2.4 ± 0.8 min. CONCLUSIONS: The QoR-15 provides a valid, extensive, and yet efficient evaluation of postoperative QoR.

Perioperative outcomes in intermediate and high-risk patients after major surgery following introduction of a dedicated perioperative medicine team: A single centre cohort study.

Intermediate and high-risk patients undergoing surgery are often managed on a surgical ward in the absence of haemodynamic or ventilatory support requirements necessitating intensive care unit or high dependency unit admission. We describe a model of care for the multidisciplinary management of selected postoperative patients and the epidemiology of patients managed using this model at a tertiary Australian hospital.Of 25,139 patients undergoing inpatient surgery at our institution over a two-year period, 506 (2%) were referred to the Perioperative Medicine team. The median age of patients referred was 74 years; 85% had an American Society of Anesthesiologists physical status ≥3, and 44% underwent emergency surgery. Major complication or death within 30 days was 44.2% (213/482). The most common complications, as defined by the American College of Surgeons National Surgical Quality Improvement Program were transfusion within 72 h (17.4%), pneumonia/aspiration pneumonitis (11.3%), and acute renal failure (10.6%); median time to Medical Emergency Team call was 146 (interquartile range 77-279) h.Sixty-six percent of referred patients (280/423) required an intervention during their time under the service. This high incidence indicates that this population of patients merits closer attention, including routine measurement and reporting of postoperative outcomes to monitor and improve quality of care at our institution as part of an integrated perioperative service. We believe that with so much current focus on perioperative medicine, it is important we translate this to clinical care by evolving traditional models of management into more innovative strategies to meet the complex demands of today's surgical patients.

Breaking the diffraction barrier outside of the optical near-field with bright, collimated light from nanometric apertures.

The optical diffraction limit has been the dominant barrier to achieving higher optical resolution in the fields of microscopy, photolithography, and optical data storage. We present here an approach toward imaging below the diffraction barrier. Through the exposure of photosensitive films placed a finite and known distance away from nanoscale, zero-mode apertures in thin metallic films, we show convincing, physical evidence that the propagating component of light emerging from these apertures shows a very strong degree of collimation well past the maximum extent of the near-field (lambda(0)/4n-lambda(0)/2n). Up to at least 2.5 wavelengths away from the apertures, the transmitted light exhibits subdiffraction limit irradiance patterns. These unexpected results are not explained by standard diffraction theory or nanohole-based "beaming" rationalizations. This method overcomes the diffraction barrier and makes super-resolution fluorescence imaging practical.

Zinc Deficiency in Men Over 50 and Its Implications in Prostate Disorders.

Research has been consistently showing the role of zinc (Zn) in prostate function. In this article, we review the current literature on the anatomy and main functions of the prostate, highlighting the role of zinc. In particular, we will review the etiology of benign prostate enlargement (BPH), its prevalence in men over 50, the likelihood of BPH becoming prostate cancer (PCa), and explain the relationship of zinc and apoptosis in the prostate cells and the implications for BPH and PCa. We present a model that explains how endogenous factors provoke excretion of zinc or limit zinc absorption, and how exogenous factors like nutrition and drugs regularly used in men over 50 can significantly decrease zinc status and thereby increase the risk of BPH. Finally, we explain how Zn amino acid (AA) complexes may be capable of avoiding antagonists and inhibitors of zinc absorption, thereby increasing the bioavailability of zinc for the necessary biological processes in the prostate.

Towards a national perioperative clinical quality registry: The diagnostic accuracy of administrative data in identifying major postoperative complications.

Accurately measuring the incidence of major postoperative complications is essential for funding and reimbursement of healthcare providers, for internal and external benchmarking of hospital performance and for valid and reliable public reporting of outcomes. Actual or surrogate outcomes data are typically obtained by one of three methods: clinical quality registries, clinical audit, or administrative data. In 2017 a perioperative registry was developed at the Alfred Hospital and mapped to administrative and clinical data. This study investigated the statistical agreement between administrative data (International Statistical Classification of Diseases and Related Health Problems (10th edition) Australian Modification codes) and clinical audit by anaesthetists in identifying major postoperative complications. The study population included 482 high-risk surgical patients referred to the Alfred Hospital anaesthesia postoperative service over two years. Clinical audit was conducted to determine the presence of major complications and these data were compared to administrative data. The main outcome was statistical agreement between the two methods, as defined by Cohen's kappa statistic. Substantial agreement was observed for five major complications, moderate agreement for three, fair agreement for six and poor agreement for two. Sensitivity and positive predictive value ranged from 0 to 100%. Specificity was above 90% for all complications. There was important variation in inter-rater agreement. For four of the five complications with substantial agreement between administrative data and clinical audit, sensitivity was only moderate (61.5%-75%). Using International Statistical Classification of Diseases and Related Health Problems (10th edition) Australian Modification codes to identify postoperative complications at our hospital has high specificity but is likely to underestimate the incidence compared to clinical audit. Further, retrospective clinical audit itself is not a highly reliable method of identifying complications. We believe a perioperative clinical quality registry is necessary to validly and reliably measure major postoperative complications in Australia for benchmarking of hospital performance and before public reporting of outcomes should be considered.

Competitive metal binding to a silicate-immobilized humic material.

The investigation of the competitive binding of metal ions to a biogenic material comprised of organic peat immobilized in a polysilicate matrix was undertaken. This material was packed into 5.0mL bed-volume columns using 40-60mesh size particles. Two separate mixtures of metal ions were studied by monitoring the solution pH and the concentration of each metal in the effluent as a function of the volume of influent introduced to the material. These mixtures contained either the metal ions Ca(2+), Mg(2+), and Cu(2+) or the ions Cu(2+), Hg(2+), and Pb(2+). A general order of binding affinities was determined to be Mg(2+)

Emerging tools for real-time label-free detection of interactions on functional protein microarrays.

The availability of extensive genomic information and content has spawned an era of high-throughput screening that is generating large sets of functional genomic data. In particular, the need to understand the biochemical wiring within a cell has introduced novel approaches to map the intricate networks of biological interactions arising from the interactions of proteins. The current technologies for assaying protein interactions--yeast two-hybrid and immunoprecipitation with mass spectrometric detection--have met with considerable success. However, the parallel use of these approaches has identified only a small fraction of physiologically relevant interactions among proteins, neglecting all nonprotein interactions, such as with metabolites, lipids, DNA and small molecules. This highlights the need for further development of proteome scale technologies that enable the study of protein function. Here we discuss recent advances in high-throughput technologies for displaying proteins on functional protein microarrays and the real-time label-free detection of interactions using probes of the local index of refraction, carbon nanotubes and nanowires, or microelectromechanical systems cantilevers. The combination of these technologies will facilitate the large-scale study of protein interactions with proteins as well as with other biomolecules.

Cell differentiation by mechanical stress.

Growth factors, hormones, and other regulatory molecules are traditionally required in tissue engineering studies to direct the differentiation of progenitor cells along specific lineages. We demonstrate that mechanical stimulation in vitro, without ligament-selective exogenous growth and differentiation factors, induces the differentiation of mesenchymal progenitor cells from the bone marrow into a ligament cell lineage in preference to alternative paths (i.e., bone or cartilage cell lineages). A bioreactor was designed to permit the controlled application of ligament-like multidimensional mechanical strains (translational and rotational strain) to the undifferentiated cells embedded in a collagen gel. The application of mechanical stress over a period of 21 days up-regulated ligament fibroblast markers, including collagen types I and III and tenascin-C, fostered statistically significant cell alignment and density and resulted in the formation of oriented collagen fibers, all features characteristic of ligament cells. At the same time, no up-regulation of bone or cartilage-specific cell markers was observed.

Functionalization-dependent induction of cellular survival pathways by CdSe quantum dots in primary normal human bronchial epithelial cells.

Quantum dots (QDs) are semiconductor nanocrystals exhibiting unique optical properties that can be exploited for many practical applications ranging from photovoltaics to biomedical imaging and drug delivery. A significant number of studies have alluded to the cytotoxic potential of these materials, implicating Cd-leaching as the causal factor. Here, we investigated the role of heavy metals in biological responses and the potential of CdSe-induced genotoxicity. Our results indicate that, while negatively charged QDs are relatively noncytotoxic compared to positively charged QDs, the same does not hold true for their genotoxic potential. Keeping QD core composition and size constant, 3 nm CdSe QD cores were functionalized with mercaptopropionic acid (MPA) or cysteamine (CYST), resulting in negatively or positively charged surfaces, respectively. CYST-QDs were found to induce significant cytotoxicity accompanied by DNA strand breakage. However, MPA-QDs, even in the absence of cytotoxicity and reactive oxygen species formation, also induced a high number of DNA strand breaks. QD-induced DNA damage was confirmed by identifying the presence of p53 binding protein 1 (53BP1) in the nuclei of exposed cells and subsequent diminishment of p53 from cytoplasmic cellular extracts. Further, high-throughput real-time PCR analyses revealed upregulation of DNA damage and response genes and several proinflammatory cytokine genes. Most importantly, transcriptome sequencing revealed upregulation of the metallothionein family of genes in cells exposed to MPA-QDs but not CYST-QDs. These data indicate that cytotoxic assays must be supplemented with genotoxic analyses to better understand cellular responses and the full impact of nanoparticle exposure when making recommendations with regard to risk assessment.

Liquid core waveguide for full imaging of electrophoretic separations.

We employed a liquid core waveguide to image both DNA electrophoresis separations and isoelectric focusing of proteins. The utility of the system is demonstrated for DNA fragment sizing and protein separations. The system utilizes the liquid-core waveguide as an efficient window for both the excitation of separated samples and the collection of light through total internal reflectance, with an ability to detect target molecules in the zeptomolar range. Scanning the excitation laser along the length of the electrophoresis capillary excites individually separated analyte bands, while the fluorescence is collected end-on by an optical fiber coupled to a photomultiplier, thus, creating an image of the separation along the length of the capillary.

Application of wavelet transforms and an approximate deconvolution method for the resolution of noisy overlapped peaks in DNA capillary electrophoresis.

A new procedure for resolving noisy overlapped peaks in DNA separations by capillary electrophoresis (CE) is developed. The procedure combines both a wavelet-based denoising method that effectively denoises the signal and a novel approximate deconvolution technique that resolves the fragment peaks and improves the ability to separate highly overlapped peaks early in the electrophoresis process. Different kinds of overlapped peaks with and without noise simulated by computer as well as some DNA experimental electropherograms were submitted to the new procedure. A second order differential operator with variable coefficients is applied to the entire electrophoresis signal at any given time and approximate deconvolutions of the individual Gaussian peaks are performed. The operator incorporates the effect of the superposition and gives exact annihilation in the neighborhood of each peak. Overlapped peaks with a resolution higher than 0.46 can be resolved directly. Also, the method can determine the peak components of signals with a signal to noise ratio higher than 1.4

Advanced bioreactor with controlled application of multi-dimensional strain for tissue engineering.

Advanced bioreactors are essential for meeting the complex requirements of in vitro engineering functional skeletal tissues. To address this need, we have developed a computer controlled bench-top bioreactor system with capability to apply complex concurrent mechanical strains to three-dimensional matrices independently housed in 24 reactor vessels, in conjunction with enhanced environmental and fluidic control. We demonstrate the potential of this new system to address needs in tissue engineering, specifically toward the development of a tissue engineered anterior cruciate ligament from human bone-marrow stromal cells (hBMSC), where complex mechanical and biochemical environment control is essential to tissue function. Well-controlled mechanical strains (resolution of < 0.1 micron for translational and < 0.1 degree for rotational strain) and dissolved oxygen tension (between 0%-95% +/- 1%) could be applied to the developing tissue, while maintaining temperature at 37 +/- 0.2 degrees C about developing tissue over prolonged periods of operation. A total of 48 reactor vessels containing cell culture medium and silk fiber matrices were run for up to 21 days under 90 degrees rotational and 2 mm translational deformations at 0.0167 Hz with only one succumbing to contamination due to a leak at an medium outlet port. Twenty-four silk fiber matrices seeded with human bone marrow stromal cells (hBMSCs) housed within reactor vessels were maintained at constant temperature (37 +/- 0.2 degrees C), pH (7.4 +/- 0.02), and pO2 (20 +/- 0.5%) over 14 days in culture. The system supported cell spreading and growth on the silk fiber matrices based on SEM characterization, as well as the differentiation of the cells into ligament-like cells and tissue (Altman et al., 2001).