Modulation of synaptic plasticity in the cortex needs to understand all the players

The prefrontal cortex (PFC) is involved in cognitive tasks such as working memory, decision making, risk assessment and regulation of attention. These functions performed by the PFC are supposed to rely on rhythmic electrical activity generated by neuronal network oscillations determined by a precise balance between excitation and inhibition balance (E/I balance) resulting from the coordinated activities of recurrent excitation and feedback and feedforward inhibition. Functional alterations in PFC functions have been associated with cognitive deficits in several pathologies such as major depression, anxiety and schizophrenia. These pathological situations are correlated with alterations of different neurotransmitter systems (i.e., serotonin (5-HT), dopamine (DA), acetylcholine...) that result in alterations of the E/I balance. The aim of this review article is to cover the basic aspects of the regulation of the E/I balance as well as to highlight the importance of the complementarity role of several neurotransmitters in the modulation of the plasticity of excitatory and inhibitory synapses. We illustrate our purpose by recent findings that demonstrate that 5-HT and DA cooperate to regulate the plasticity of excitatory and inhibitory synapses targeting layer 5 pyramidal neurons (L5PyNs) of the PFC and to fine tune the E/I balance. Using a method based on the decomposition of the synaptic conductance into its excitatory and inhibitory components, we show that concomitant activation of D1-like receptors (D1Rs) and 5-HT1ARs, through a modulation of NMDA receptors, favors long term potentiation (LTP) of both excitation and inhibition and consequently does not modify the E/I balance. We also demonstrate that activation of D2-receptors requires functional 5-HT1ARs to shift the E-I balance towards more inhibition and to favor long term depression (LTD) of excitatory synapses through the activation of glycogen synthase kinase 3β (GSK3β). This cooperation between different neurotransmitters is particularly relevant in view of pathological situations in which alterations of one neurotransmitter system will also have consequences on the regulation of synaptic efficacy by other neurotransmitters. This opens up new perspectives in the development of therapeutic strategies for the pharmacological treatment of neuronal disorders

Risks and risk mitigation in waste-work: A qualitative study of informal waste workers in Nepal

Objectives To explore how informal waste workers (IWWs) working in Kathmandu Valley perceive risks associated with waste work and what they do to mitigate them. Study design Qualitative Study Design. Methods A mix of one-to-one semi-structured interviews (n ​= ​18) and focus group discussions (n ​= ​4) with IWWs were undertaken. Participants were recruited purposively using snowball sampling. All interviews and discussions were audio-recorded, transcribed verbatim, translated and subsequently analysed thematically. Results The IWWs perceived discrimination and health risks as the main risks associated with waste work. IWWs reported considerable stigma and discrimination not only from the wider society but also from family members and within their own profession. Similarly, the occupational risks most frequently recognized were physical injuries and cuts from working with waste. However, the potential risks from hazardous chemicals present in or generated from waste were not articulated by participants. Mitigation strategies to combat the risks included avoidance, greater care and the use of informal means of “protection”. Awareness of the importance of personal protective equipment (PPE) was limited. The key barriers to the use of PPE identified included costs, the lack of easy availability of PPE and the inconvenience of working with PPE. Conclusions The vulnerability of informal waste workers in Nepal is multifaceted. A range of policy and regulatory measures, along with interventions that promote greater social inclusion and occupational support are needed to promote IWW’s health and safety

Improvement of continuous-variable quantum key distribution systems by using optical preamplifiers

Continuous-variable quantum key distribution protocols, based on Gaussian modulation of the quadratures of coherent states, have been implemented in recent experiments. A present limitation of such systems is the finite efficiency of the detectors, which can in principle be compensated for by the use of classical optical preamplifiers. Here we study this possibility in detail, by deriving the modified secret key generation rates when an optical parametric amplifier is placed at the output of the quantum channel. After presenting a general set of security proofs, we show that the use of preamplifiers does compensate for all the imperfections of the detectors when the amplifier is optimal in terms of gain and noise. Imperfect amplifiers can also enhance the system performance, under conditions which are generally satisfied in practice.Comment: 11 pages, 7 figures, submitted to J. Phys. B (special issue on Few Atoms Optics

Field test of a continuous-variable quantum key distribution prototype

We have designed and realized a prototype that implements a continuous-variable quantum key distribution protocol based on coherent states and reverse reconciliation. The system uses time and polarization multiplexing for optimal transmission and detection of the signal and phase reference, and employs sophisticated error-correction codes for reconciliation. The security of the system is guaranteed against general coherent eavesdropping attacks. The performance of the prototype was tested over preinstalled optical fibres as part of a quantum cryptography network combining different quantum key distribution technologies. The stable and automatic operation of the prototype over 57 hours yielded an average secret key distribution rate of 8 kbit/s over a 3 dB loss optical fibre, including the key extraction process and all quantum and classical communication. This system is therefore ideal for securing communications in metropolitan size networks with high speed requirements.Comment: 15 pages, 6 figures, submitted to New Journal of Physics (Special issue on Quantum Cryptography

Feasibility of quantum key distribution through dense wavelength division multiplexing network

In this paper, we study the feasibility of conducting quantum key distribution (QKD) together with classical communication through the same optical fiber by employing dense-wavelength-division-multiplexing (DWDM) technology at telecom wavelength. The impact of the classical channels to the quantum channel has been investigated for both QKD based on single photon detection and QKD based on homodyne detection. Our studies show that the latter can tolerate a much higher level of contamination from the classical channels than the former. This is because the local oscillator used in the homodyne detector acts as a "mode selector" which can suppress noise photons effectively. We have performed simulations based on both the decoy BB84 QKD protocol and the Gaussian modulated coherent state (GMCS) QKD protocol. While the former cannot tolerate even one classical channel (with a power of 0dBm), the latter can be multiplexed with 38 classical channels (0dBm power each channel) and still has a secure distance around 10km. Preliminary experiment has been conducted based on a 100MHz bandwidth homodyne detector.Comment: 18 pages, 5 figure

The health risks of informal waste workers in the Kathmandu Valley: a cross-sectional survey

Objective: To describe the health and occupational risks of informal waste workers (IWWs) in the Kathmandu Valley and explore the factors associated with not using personal protective equipment (PPE). Study design: This is a cross-sectional survey of IWWs. Methods: Data were collected on the health and occupational risks of adult IWWs working on waste sites in the Kathmandu Valley and in the adjacent Nuwakot district, Nepal, in November 2017, through convenience sampling. Using a standardized health assessment questionnaire, face-to-face interviews were undertaken to record sociodemographic data, indicators of general and occupational health, data on healthcare access and use, physical risks, perception of occupational risks and use of PPE. Associations between use of PPE and gender, age, education, country of origin, injury and perception of occupational risks were examined using multivariate logistic regression analyses. Results: In 1278 surveyed IWWs, prevalent physical risks included injuries (66.2% in the previous 12 months), and the main reported symptoms were respiratory in nature (69.9% in the previous 3 months). Most prevalent injuries were glass cuts (44.4%) and metal cuts (43.9%). Less than half of the IWWs (46.8%) had been vaccinated against tetanus and 7.5% against hepatitis B. The work was considered as ‘risky’ by 72.5% of IWWs, but 67.6% did not use PPE. Non-use of PPE was independently associated with male gender (odds ratio [OR] 2.19; P < 0.001), Indian origin (OR 1.35; P = 0.018), older age (OR 2.97 for more than the age of 55 years; P = 0.007) and low perception of occupational risks (OR 2.41; P < 0.001). Low perception of occupational risk was associated with older age (55 + years) and the lack of receipt of information on the risks. Conclusions: IWWs are at increased risk of injury in their work, yet are poorly protected in relation to vaccine-preventable infections and workwear. The results suggest that information is important in relation to perception of occupational risk, which in turn is associated with the use of PPE. There is a need for policymakers and public health practitioners to have a robust understanding of the needs and vulnerabilities of this group, as well as identify effective interventions that can be taken to safeguard the health and welfare of IWWs

Mental health risks among informal waste workers in Kathmandu Valley, Nepal

Informal waste workers are a vulnerable population group who are often socio-economically marginalized and disadvantaged, with more likelihood of experiencing ill health than the general population. To explore the determinants of mental ill health in this group, we conducted a cross-sectional survey of 1278 informal waste-workers in Nepal in 2017, using a demographic health assessment questionnaire and a modified Patient Health Questionnaire (PHQ-9). We looked at the potential associations between various exposure factors and mental health outcomes and found that 27.4% of waste-workers had depressive symptoms, more likely to be reported by female (OR 2.290), older person (OR 7.757), divorced/separated (5.859), and those with ill health (OR 2.030), or disability (OR 3.562). Waste-workers with access to social protection (OR 0.538) and financial savings (OR 0.280) were less likely to have depressive symptoms. There are key risk factors that may enable identification of particularly vulnerable persons within this group and also protective factors that may help improve their mental health resilience

Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides

BACKGROUND: The alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment derived from the C-terminal region of the enzyme acetylcholinesterase. This investigation was undertaken to determine if the functional changes observed could be attributed to peptide binding interaction with the alpha7-nAChR, or peptide modulation of receptor expression. METHODOLOGY/PRINCIPAL FINDINGS: This study provides evidence that two peptides derived from the C-terminus of acetylcholinesterase, not only selectively displace specific bungarotoxin binding at the alpha7-nAChR, but also alter receptor binding properties for its familiar ligands, including the alternative endogenous agonist choline. Of more long-term significance, these peptides also induce upregulation of alpha7-nAChR mRNA and protein expression, as well as enhancing receptor trafficking to the plasma membrane. CONCLUSIONS/SIGNIFICANCE: The results reported here demonstrate a hitherto unknown relationship between the alpha7-nAChR and the non-enzymatic functions of acetylcholinesterase, mediated independently by its C-terminal domain. Such an interaction may prove valuable as a pharmacological tool, prompting new approaches for understanding, and combating, the process of neurodegeneration

Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides

BACKGROUND: The alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment derived from the C-terminal region of the enzyme acetylcholinesterase. This investigation was undertaken to determine if the functional changes observed could be attributed to peptide binding interaction with the alpha7-nAChR, or peptide modulation of receptor expression. METHODOLOGY/PRINCIPAL FINDINGS: This study provides evidence that two peptides derived from the C-terminus of acetylcholinesterase, not only selectively displace specific bungarotoxin binding at the alpha7-nAChR, but also alter receptor binding properties for its familiar ligands, including the alternative endogenous agonist choline. Of more long-term significance, these peptides also induce upregulation of alpha7-nAChR mRNA and protein expression, as well as enhancing receptor trafficking to the plasma membrane. CONCLUSIONS/SIGNIFICANCE: The results reported here demonstrate a hitherto unknown relationship between the alpha7-nAChR and the non-enzymatic functions of acetylcholinesterase, mediated independently by its C-terminal domain. Such an interaction may prove valuable as a pharmacological tool, prompting new approaches for understanding, and combating, the process of neurodegeneration