Recent Advances in Metal Complexes for Antimicrobial Photodynamic Therapy

Antimicrobial resistance (AMR) is a growing global problem with more than 1 million deaths due to AMR infection in 2019 alone. New and innovative therapeutics are required to overcome this challenge. Antimicrobial photodynamic therapy (aPDT) is a rapidly growing area of research poised to provide much needed help in the fight against AMR. aPDT works by administering a photosensitizer (PS) that is activated only when irradiated with light, allowing high spatiotemporal control and selectivity. The PS typically generates reactive oxygen species (ROS), which can damage a variety of key biological targets, potentially circumventing existing resistance mechanisms. Metal complexes are well known to display excellent optoelectronic properties, and recent focus has begun to shift towards their application in tackling microbial infections. Herein, we review the last five years of progress in the emerging field of small-molecule metal complex PSs for aPDT.     

Acceleration of changes in session impact during contrasting time-limited psychotherapies.

Following the suggestion that therapeutic change is accelerated in time-limited psychotherapy, this study investigated the across-session patterns of session impact in the treatments of 117 depressed clients who were randomly allocated to 8 or 16 sessions of cognitive-behavioral (CB) or psychodynamic-interpersonal (PI) therapy. After each session, all clients completed the Session Evaluation Questionnaire and 75 of the clients completed the Session Impacts Scale. Session ratings indicated that sessions were perceived increasingly positively on most impact dimensions (e.g., session depth and smoothness, relationship with the therapist, feelings of understanding and problem solving, postsession positive mood) as treatment progressed. Early in treatment, PI therapy sessions were less smooth (i.e., more tense and uncomfortable) and less focused on problem solving, but PI sessions changed more rapidly than CB sessions on these dimensions, so that later in treatment, sessions of both treatments were equivalently positive. In both treatments, the trend toward more positive sessions was more rapid (i.e., the across-session slope was steeper) in 8-session treatments than in 16 session treatments. Such accelerated changes in session impact may reflect the suggested acceleration … (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Murine Oral‐Exposure Model for Nano‐ and Micro‐Particulates: Demonstrating Human Relevance with Food‐Grade Titanium Dioxide

Human exposure to persistent, nonbiological nanoparticles and microparticles via the oral route is continuous and large scale (10¹²–10¹³ particles per day per adult in Europe). Whether this matters or not is unknown but confirmed health risks with airborne particle exposure warns against complacency. Murine models of oral exposure will help to identify risk but, to date, lack validation or relevance to humans. This work addresses that gap. It reports i) on a murine diet, modified with differing concentrations of the common dietary particle, food grade titanium dioxide (fgTiO₂), an additive of polydisperse form that contains micro‐ and nano‐particles, ii) that these diets deliver particles to basal cells of intestinal lymphoid follicles, exactly as is reported as a “normal occurrence” in humans, iii) that confocal reflectance microscopy is the method of analytical choice to determine this, and iv) that food intake, weight gain, and Peyer's patch immune cell profiles, up to 18 weeks of feeding, do not differ between fgTiO₂‐fed groups or controls. These findings afford a human‐relevant and validated oral dosing protocol for fgTiO₂ risk assessment as well as provide a generalized platform for application to oral exposure studies with nano‐ and micro‐particles.     

Resources for research: the 1991 census of population

The author discusses population censuses in general and describes their utility for research, with a focus on the arrangements under which researchers at institutes of higher education are being provided with data sets from the census. "Although much of the discussion will be specific to the United Kingdom, many of the issues raised will be important in other countries."     

Chronic inhibition of NOS does not prevent plasticity of rat somatosensory (S1) cortex following deafferentation

Nitric oxide (NO) has been proposed as an intercellular messenger mediating postsynaptic to presynaptic information transfer in the induction of long-term potentiation. A number of studies support the possible involvement of NO in synaptic plasticity. NO may have a role in synaptogenesis and synaptic plasticity in developing rat brain and may play a fundamental part in the process of regeneration, plasticity, and retargeting of axons following injury. We examined the possible role of NO on plasticity in the rat first somatosensory cortex with [14C]2-deoxyglucose (2-DG) autoradiography in rats treated daily with l-nitroarginine (l-NA) following neonatal unilateral vibrissae deafferentation. After 6 weeks of l-NA treatment, the local cerebral glucose utilization (LCGU) and the spatial extent of the metabolic activation following stimulation of the spared whisker was measured. NOS catalytic activity exhibited significant inhibition throughout the treatment period. Vibrissae deafferentation produced a small but not statistically significant increase of LCGU in the vibrissa activated C3 barrel, and l-NA treatment did not alter the activation of LCGU in the deafferented cortex following whisker stimulation. Additionally, l-NA treatment did not alter the area of metabolic activation on either the non-deafferented side or the deafferented side. Deafferentation produced a 298% increase in the metabolic representation of the spared C3 barrel following stimulation in the saline treated animals, a 257% increase in the chronically l-NA treated animals, and a 256% increase in the short-term treated animals, all with respect to the response in the non-deafferented cortex. Metabolic plasticity in the barrel cortex was not attenuated by l-NA treatment. These results show that nitric oxide does not play a major role on developmental cortical plasticity induced by vibrissae deafferentation in the rat.     

Analysis and design of fuzzy control systems using dynamicfuzzy-state space models

A discrete-time fuzzy control system which is composed of a dynamic fuzzy model and a fuzzy-state feedback controller is proposed. Stability of the fuzzy control system is discussed and two sufficient conditions to guarantee the stability of the system are given in terms of uncertain linear system theory. An algorithm is developed to check the stability condition. The controller design method is divided into two procedures, one is to get the state feedback matrix by linear system theory in every local rule map; the other is to determine conditions of global stability by using a nonlinear analysis method. Two examples are used to show the design method     

Covariation of activity in visual and prefrontal cortex associated with subjective visual perception

Visual areas of the occipitotemporal pathway are thought to be essential for the conscious perception of objects, but the contribution of other cortical regions and the neural mechanisms leading to the awareness of a visual stimulus remain unclear. By using functional MRI in humans exposed to bistable viewing conditions, subjective visual perception was related to covariation of activity in multiple extrastriate ventral, parietal, and prefrontal cortical areas. The coordination of activity among these regions was not linked to external sensory or motor events; rather, it reflected internal changes in perception and varied in strength with the frequency of perceptual events, suggesting that functional interactions between visual and prefrontal cortex may contribute to conscious vision. Because similar cortical systems have been implicated in short-term memory and motor planning, the results also imply that related neural processes may underlie visual awareness and the organization of voluntary behavior contingent on sensory cues.     

Ionic mechanisms of action of neurotensin in acutely dissociated neurons from the diagonal band of Broca of the rat

Whole cell recordings were performed on acutely dissociated neurons from the horizontal limb of the diagonal band of Broca (hDBB) from rats to elucidate the ionic mechanisms of action of neurotensin. Neurotensin caused a decrease in whole cell voltage-activated outward currents and failed to elicit a response when Ca2+ influx was blocked by changing the external solution to the one containing 0 mM Ca2+ and 50 microM Cd2+, suggesting the involvement of Ca2+-dependent conductances. Charybdotoxin, a specific blocker of voltage-sensitive calcium-activated K+ channels (IC), caused a decrease in outward currents comparable with that caused by blocking calcium influx and occluded the neurotensin-induced decrease in outward currents. Similarly, 50 microM tetraethylammonium ions also blocked the neurotensin response. Also neurotensin reduced whole cell barium currents (IBa) and calcium currents (ICa). Amiloride and omega-conotoxin GVIA, but not nimodipine, were able to eliminate the neurotensin-induced decrease in IBa. Thus T- and N- but not L-type calcium channels are subject to modulation by neurotensin, and this may account for its effects on IC. The predicted changes in action potential as a result of the blockade of currents through calcium channels culminating into changes in IC were confirmed in the bridge current-clamp recordings. Specifically, neurotensin application led to depolarization of the resting membrane potential, broadening of spike and a decrease in afterhyperpolarization and accommodation. These alterations in action potential characteristics that resulted in increased firing rate and excitability of the hDBB neurons also were produced by application of charybdotoxin. Neurotensin effects on these properties were occluded by 2 - [(1 - 7 - chloro - 4 - quinolinyl) - 5 - (2, 6 - di - methoxyphenyl) pyrazol-3-yl) carbonylamino] tricyclo (3.3.1.1.)decan-2-carboxylic acid, a nonpeptide high-affinity neurotensin receptor antagonist. Neurotensin blockade of IC, possibly through ICa, is a potential physiological mechanism whereby this peptide may evoke alterations in the cortical arousal, sleep-wake cycle, and theta rhythm.