Enhanced Recovery After Surgery in Laparoscopic Cholecystectomy - A Systematic Review.

BACKGROUND AND AIM: Enhanced Recovery After Surgery (ERAS) is a modern concept that aims to improve the perioperative patient care by implementing an evidence-based, patient-centered team approach. This paper aims to analyze the outcome, variations and limits of the ERAS-protocols used for laparoscopic cholecystectomy. Methods: We performed a systematic review on PubMed, Google Scholar, Web of Science to document the outcomes of applying various ERAS protocols in laparoscopic cholecystectomy (LC). After applying the inclusion and exclusion criteria, 8 papers, totaling 1453 patients that underwent LC, were included in the qualitative analysis. ERAS-protocols applied in those studies include various pre-, intra- and postoperative measures intended to boost the surgical recovery of the patients and shorten their hospital stay, without exposing them to hazardous encounters. Results: Patients undergoing laparoscopic cholecystectomy within an ERAS-specific protocol are proven to have lower levels of postoperative pain, nausea and vomiting, with no statistically significant risk of postoperative complications. The postoperative results show that ERAS-laparoscopic cholecystectomy is a feasible and safe procedure, that may shorten the postoperative recovery after LC. Conclusions: Further studies are needed to establish a consensus regarding the perioperative protocol, before implementing ERAS for LC in clinical routine.

Clinical outcomes of total hip arthroplasty after femoral neck fractures vs. osteoarthritis at one year follow up-A comparative, retrospective study.

PURPOSE: The objective of the study is to determine if there was a difference in medical complications and in-hospital mortality among the patients who underwent THA for femoral neck fracture relative to same procedure for elective patients with coxarthrosis. METHODS: We compared characteristics and short-term outcomes during the rehabilitative postsurgical period. We included all patients older than 45 years who underwent THA for primary/secondary hip arthritis and displaced femoral neck fractures type Garden III and IV. Clinical examination, functional outcome and radiographic evaluation were performed during follow-up. Patients were evaluated at the following time points: preoperatively, postoperatively at three days, six weeks, 12 weeks and one year and we registered Visual Analogue Scale (VAS) pain score, Harris Hip Score (HHS), the Western Ontario McMaster Osteoarthritis Index (WOMAC), internal and external rotation of the hip and operated limb length compared with the opposite. RESULTS: There is no significant statistically differences between the two groups regarding the preoperative comorbidities. The frequencies of patients experiencing in-hospital and 30-day postoperative complications were generally low and same in groups we studied. The mean quantity of surgical blood loos during the operation was significantly higher in the hip fracture group compared with elective patient group with OA (340.09 ± 86.03 vs 309.43 ± 102.52). With respect to postoperative recovery the patients with THA after FNF were mobilized by active walking a little bit faster as the patient with OA (2.77 ± 1.18 days vs 3.1 ± 1.14 days). The average inpatient hospital length of stay after THA for OA was 11.07 days compared to 13.41 days following a THA for FNF. CONCLUSION: Our study showed that THA for treatment of an acute fracture of the femoral neck in an elderly patient can provide results comparable to those of patients who received THA for OA and we found that the results are similar.

Beta vulgaris L.-A Source with a Great Potential in the Extraction of Natural Dyes Intended for the Sustainable Dyeing of Wool.

Beta vulgaris L. is a biennial plant easily accessible all over the world, rich in various biologically active compounds, especially a class of extremely bioactive pigments known as betalains. These dyes predominate in the pulp and peels of beetroot, which is why they can be valorized in food, medicine or in the textile industry. In this work, betalains extractions were carried out applying 3 sustainable options: (1) dissolving/solubilizing betalains in water; (2) extraction under pressure; (3) extraction assisted by an enzyme/pectinase. The obtained extracts were analyzed in the UV-Vis domain, which allowed their characterization by determining the total monomeric anthocyanins, color density (control), polymeric density and browning index. The HPLC-MS analysis highlighted the extracts composition. The colors characteristics were determined through CIELab measurements. The performances of these 3 extracts, during green dyeing (without mordants), were evaluated according to the color characteristics (L*, a*, b* and K/S) of the dyed wool samples under different conditions: pH, temperature, duration of dyeing and volume of extract and stabilizers (Vitamin E and EDTA). Betalains can be considered acid dyes, with a low affinity for wool, which in a pronounced acidic environment dye the wool in an intense, uniform way and with good resistance to washing and rubbing.

Non-Destructive X-ray Characterization of a Novel Joining Method Based on Laser-Melting Deposition for AISI 304 Stainless Steel.

In this study, an application of the laser-melting deposition additive manufacturing technique as a welding method has been studied for the laser welding (LW) of AISI 304 stainless steel, specifically 0.4 mm and 0.5 mm thick sheets. The welding was carried out without and with filler material. Inconel 718 powder particles were used as filler material in the second case. A series of experiments were designed by changing the process parameters to identify the effect of operating conditions on the weld width, depth, and height. The welds were examined through metallographic experiments performed at various cross-sections to identify the defects and pores. All the deposited welds were passed through a customized mini-focus X-ray system to analyze the weld uniformities. The optimal operating conditions were determined for 0.4 mm and 0.5 mm sheets for the LW with and without filler material. It was found that laser power, laser scanning speed, powder flow rate, and helium to argon gases mixture-control the weld bead dimensions and quality. X-ray analyses showed that the optimal operating conditions gave the least peak value of non-uniformity in the laser welds. This study opens a new window for laser welding via additive manufacturing with X-ray monitoring.

Keyhole Formation by Laser Drilling in Laser Powder Bed Fusion of Ti6Al4V Biomedical Alloy: Mesoscopic Computational Fluid Dynamics Simulation versus Mathematical Modelling Using Empirical Validation.

In the laser powder bed fusion (LPBF) process, the operating conditions are essential in determining laser-induced keyhole regimes based on the thermal distribution. These regimes, classified into shallow and deep keyholes, control the probability and defects formation intensity in the LPBF process. To study and control the keyhole in the LPBF process, mathematical and computational fluid dynamics (CFD) models are presented. For CFD, the volume of fluid method with the discrete element modeling technique was used, while a mathematical model was developed by including the laser beam absorption by the powder bed voids and surface. The dynamic melt pool behavior is explored in detail. Quantitative comparisons are made among experimental, CFD simulation and analytical computing results leading to a good correspondence. In LPBF, the temperature around the laser irradiation zone rises rapidly compared to the surroundings in the powder layer due to the high thermal resistance and the air between the powder particles, resulting in a slow travel of laser transverse heat waves. In LPBF, the keyhole can be classified into shallow and deep keyhole mode, controlled by the energy density. Increasing the energy density, the shallow keyhole mode transforms into the deep keyhole mode. The energy density in a deep keyhole is higher due to the multiple reflections and concentrations of secondary reflected beams within the keyhole, causing the material to vaporize quickly. Due to an elevated temperature distribution in deep keyhole mode, the probability of pores forming is much higher than in a shallow keyhole as the liquid material is close to the vaporization temperature. When the temperature increases rapidly, the material density drops quickly, thus, raising the fluid volume due to the specific heat and fusion latent heat. In return, this lowers the surface tension and affects the melt pool uniformity.

Green Chemistry in the Extraction of Natural Dyes from Colored Food Waste, for Dyeing Protein Textile Materials.

The beetroot peels can be a sustainable source of betalains that can dye the wool materials through green processes based on low water and energy consumption. Green chemistry in the extraction of betalains from colored food waste/peels from red beetroot involved the use of water as a solvent, without other additives. In order for the extract obtained to be able to dye the wool, it was necessary to functionalize betalains or even the wool. Three types of sustainable functionalizations were performed, with (1) acetic acid; (2) ethanol; and (3) arginine. For each functionalization, the mechanism that can justify dyeing the wool in intense colors was elucidated. The characterization of the extract was performed with the data provided by UV-VIS and HPLC-MS analyses. The characterization of the wool dyed with the extract obtained from the red beetroot peels was possible due to the information resulting from the FTIR and CIELab analyses. The functionalizations of betalains and wool in acid environments lead to the most intense red colors. The color varies depending on the pH and the concentration of betalains.

Sustainable Functionalization of PAN to Improve Tinctorial Capacity.

This study may open a new way to obtain the coloration of a polymer during functionalization. Two polyacrylonitrile (PAN) polymers in the form of textile fibers (Melana and Dralon L) were subjected to functionalization treatments in order to improve the dyeing capacity. The functionalizations determined by an organo-hypervalent iodine reagent developed in situ led to fiber coloration without using dyes. KIO3 was formed in situ from the interaction of aqueous solutions of 3-9% KOH with 3-9% I2, at 120 °C. The yellow-orange coloration appeared as a result of the transformations in the chemical structure of each functionalized polymer, with the formation of iodinehydrin groups. The degree of functionalization directly influenced the obtained color. The results of the Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), Map and Temogravimetric Analysis (TG) plus Differential Thermal (DTA) analyses indicated the presence of new functional groups, such as iodine-oxime. The X-ray diffraction (XRD) analysis confirmed the change of the crystalline/amorphous ratio in favor of the former. The new groups introduced by functionalization make it possible to dye with classes of dyes specific to these groups, but not specific to PAN fibers, thus improving their dyeing capacity.

A State-of-the-Art Review on Integral Transform Technique in Laser-Material Interaction: Fourier and Non-Fourier Heat Equations.

Heat equations can estimate the thermal distribution and phase transformation in real-time based on the operating conditions and material properties. Such wonderful features have enabled heat equations in various fields, including laser and electron beam processing. The integral transform technique (ITT) is a powerful general-purpose semi-analytical/numerical method that transforms partial differential equations into a coupled system of ordinary differential equations. Under this category, Fourier and non-Fourier heat equations can be implemented on both equilibrium and non-equilibrium thermo-dynamical processes, including a wide range of processes such as the Two-Temperature Model, ultra-fast laser irradiation, and biological processes. This review article focuses on heat equation models, including Fourier and non-Fourier heat equations. A comparison between Fourier and non-Fourier heat equations and their generalized solutions have been discussed. Various components of heat equations and their implementation in multiple processes have been illustrated. Besides, literature has been collected based on ITT implementation in various materials. Furthermore, a future outlook has been provided for Fourier and non-Fourier heat equations. It was found that the Fourier heat equation is simple to use but involves infinite speed heat propagation in comparison to the non-Fourier heat equation and can be linked with the Two-Temperature Model in a natural way. On the other hand, the non-Fourier heat equation is complex and involves various unknowns compared to the Fourier heat equation. Fourier and Non-Fourier heat equations have proved their reliability in the case of laser-metallic materials, electron beam-biological and -inorganic materials, laser-semiconducting materials, and laser-graphene material interactions. It has been identified that the material properties, electron-phonon relaxation time, and Eigen Values play an essential role in defining the precise results of Fourier and non-Fourier heat equations. In the case of laser-graphene interaction, a restriction has been identified from ITT. When computations are carried out for attosecond pulse durations, the laser wavelength approaches the nucleus-first electron separation distance, resulting in meaningless results.

3D Printing at Micro-Level: Laser-Induced Forward Transfer and Two-Photon Polymerization.

Laser-induced forward transfer (LIFT) and two-photon polymerization (TPP) have proven their abilities to produce 3D complex microstructures at an extraordinary level of sophistication. Indeed, LIFT and TPP have supported the vision of providing a whole functional laboratory at a scale that can fit in the palm of a hand. This is only possible due to the developments in manufacturing at micro- and nano-scales. In a short time, LIFT and TPP have gained popularity, from being a microfabrication innovation utilized by laser experts to become a valuable instrument in the hands of researchers and technologists performing in various research and development areas, such as electronics, medicine, and micro-fluidics. In comparison with conventional micro-manufacturing methods, LIFT and TPP can produce exceptional 3D components. To gain benefits from LIFT and TPP, in-detail comprehension of the process and the manufactured parts' mechanical-chemical characteristics is required. This review article discusses the 3D printing perspectives by LIFT and TPP. In the case of the LIFT technique, the principle, classification of derivative methods, the importance of flyer velocity and shock wave formation, printed materials, and their properties, as well as various applications, have been discussed. For TPP, involved mechanisms, the difference between TPP and single-photon polymerization, proximity effect, printing resolution, printed material properties, and different applications have been analyzed. Besides this, future research directions for the 3D printing community are reviewed and summarized.

Thermal Nonlinear Klein-Gordon Equation for Nano-/Micro-Sized Metallic Particle-Attosecond Laser Pulse Interaction.

In this study, a rigorous analytical solution to the thermal nonlinear Klein-Gordon equation in the Kozlowski version is provided. The Klein-Gordon heat equation is solved via the Zhukovsky "state-of-the-art" mathematical techniques. Our study can be regarded as an initial approximation of attosecond laser-particle interaction when the prevalent phenomenon is photon-electron interaction. The electrons interact with the laser beam, which means that the nucleus does not play a significant role in temperature distribution. The particle is supposed to be homogenous with respect to thermophysical properties. This theoretical approach could prove useful for the study of metallic nano-/micro-particles interacting with attosecond laser pulses. Specific applications for Au "nano" particles with a 50 nm radius and "micro" particles with 110, 130, 150, and 1000 nm radii under 100 attosecond laser pulse irradiation are considered. First, the cross-section is supposed to be proportional to the area of the particle, which is assumed to be a perfect sphere of radius R or a rotation ellipsoid. Second, the absorption coefficient is calculated using a semiclassical approach, taking into account the number of atoms per unit volume, the classical electron radius, the laser wavelength, and the atomic scattering factor (10 in case of Au), which cover all the basic aspects for the interaction between the attosecond laser and a nanoparticle. The model is applicable within the 100-2000 nm range. The main conclusion of the model is that for a range inferior to 1000 nm, a competition between ballistic and thermal phenomena occurs. For values in excess of 1000 nm, our study suggests that the thermal phenomena are dominant. Contrastingly, during the irradiation with fs pulses, this value is of the order of 100 nm. This theoretical model's predictions could be soon confirmed with the new EU-ELI facilities in progress, which will generate pulses of 100 as at a 30 nm wavelength.

Multifunctional Finishing of Cotton with Compounds Derived from MCT-ß-CD and Quantification of Effects Using MLR Statistical Analysis.

Multifunctionalization of cotton using a single product has not been made until now. Such a product was synthesized using compounds with multiple functions (glyoxal, ethylenediamine (ED) and monochlorotriazinyl-ß-cyclodextrin (MCT-ß-CD)), under different mass ratios. Obtaining this multifunctional derivative has been confirmed by spectroscopic analyses (1H-NMR and FTIR) and a scanning electron microscope (SEM). Treatment of cotton with the MCT-ß-CD derivative (D-CD) has been realized with the pad dry-cure technology. The presence of this multifunctional derivative on cotton was highlighted with spectroscopic (FTIR, EDAX, XRD) and thermoanalytical (DSC) methods. The objective of treating cotton with D-CD was to achieve four simultaneous effects: large wrinkle recovery angle (WRA), hydrophilicity, antibacterial capacity and a good breaking resistance. This objective has been achieved, so the garments that will be manufactured with such multifunctional cotton will be more comfortable. The efficiency of treatments with D-CD was marked out by multiple linear regression (MLR) and certain quality indices. Using MLR, the behavior of the treated cotton was mathematically modeled and the stationary/optimal points corresponding to each effect were calculated. Quality indices have been calculated and all final samples had values higher than 1, which confirmed the positive effects exerted by D-CDs on cotton.

Metal Matrix Composites Synthesized by Laser-Melting Deposition: A Review.

Metal matrix composites (MMCs) present extraordinary characteristics, including high wear resistance, excellent operational properties at elevated temperature, and better chemical inertness as compared to traditional alloys. These properties make them prospective candidates in the fields of aerospace, automotive, heavy goods vehicles, electrical, and biomedical industries. MMCs are challenging to process via traditional manufacturing techniques, requiring high cost and energy. The laser-melting deposition (LMD) has recently been used to manufacture MMCs via rapid prototyping, thus, solving these drawbacks. Besides the benefits mentioned above, the issues such as lower ultimate tensile strength, yield strength, weak bonding between matrix and reinforcements, and cracking are still prevalent in parts produced by LMD. In this article, a detailed analysis is made on the MMCs manufactured via LMD. An illustration is presented on the LMD working principle, its classification, and dependent and independent process parameters. Moreover, a brief comparison between the wire and powder-based LMDs has been summarized. Ex- and in-situ MMCs and their preparation techniques are discussed. Besides this, various matrices available for MMCs manufacturing, properties of MMCs after printing, possible complications and future research directions are reviewed and summarized.

Prototype Orthopedic Bone Plates 3D Printed by Laser Melting Deposition.

Laser melting deposition is a 3D printing method usually studied for the manufacturing of machine parts in the industry. However, for the medical sector, although feasible, applications and actual products taking advantage of this technique are only scarcely reported. Therefore, in this study, Ti6Al4V orthopedic implants in the form of plates were 3D printed by laser melting deposition. Tuning of the laser power, scanning speed and powder feed rate was conducted, in order to obtain a continuous deposition after a single laser pass and to diminish unwanted blown powder, stuck in the vicinity of the printed elements. The fabrication of bone plates is presented in detail, putting emphasis on the scanning direction, which had a decisive role in the 3D printing resolution. The printed material was investigated by optical microscopy and was found to be dense, with no visible pores or cracks. The metallographic investigations and X-ray diffraction data exposed an unusual biphasic α+ß structure. The energy dispersive X-ray spectroscopy revealed a composition very similar to the one of the starting powder material. The mapping of the surface showed a uniform distribution of elements, with no segregations or areas with deficient elemental distribution. The in vitro tests performed on the 3D printed Ti6Al4V samples in osteoblast-like cell cultures up to 7 days showed that the material deposited by laser melting is cytocompatible.

OSF-Builder: A New Tool for Constructing and Representing Evolutionary Histories Involving Introgression.

Introgression is an evolutionary process which provides an important source of innovation for evolution. Although various methods have been used to detect introgression, very few methods are currently available for constructing evolutionary histories involving introgression. In this article, we propose a new method for constructing such evolutionary histories whose starting point is a species forest (consisting of a collection of lineage trees, usually arising as a collection of clades or monophyletic groups in a species tree), and a gene tree for a specific allele of interest, or allele tree for short. Our method is based on representing introgression in terms of a certain "overlay" of the allele tree over the lineage trees, called an overlaid species forest (OSF). OSFs are similar to phylogenetic networks although a key difference is that they typically have multiple roots because each monophyletic group in the species tree has a different point of origin. Employing a new model for introgression, we derive an efficient algorithm for building OSFs called OSF-Builder that is guaranteed to return an optimal OSF in the sense that the number of potential introgression events is minimized. As well as using simulations to assess the performance of OSF-Builder, we illustrate its use on a butterfly data set in which introgression has been previously inferred. The OSF-Builder software is available for download from https://www.uea.ac.uk/computing/software/OSF-Builder.

Difficulties in histopathology diagnosis and treatment of depressive disorder of breast cancer in male - clinical case presentation.

Breast cancer is less common among men than among women (about 1 in 100) and it is considered a rare disease but the evolution is significantly influenced by depression and distress. We present the case of a 63-year-old patient that was diagnosed in another Clinic with squamous skin carcinoma, but, after complete resection in our Hospital, it was proven to be breast cancer. At diagnosis, computed tomography (CT) scan showed local disease. Adjuvant treatment, consisting in chemotherapy and radiotherapy, was administered. At the beginning of hormonal therapy, the patient had a new CT scan that showed liver and bone metastases. The patient started palliative hormonal treatment with bisphosphonates. The aim of the study was to highlight both the importance of early diagnosis and treatment and the aggressiveness of male breast cancer compared with female. Depressive disorder and social distress worsens the prognosis and quality of life. Male with breast cancer has identity difficulties, body image disturbances and secondary distress.

Laser-direct writing by two-photon polymerization of 3D honeycomb-like structures for bone regeneration.

A major limitation of existing 3D implantable structures for bone tissue engineering is that most of the cells rapidly attach on the outer edges of the structure, restricting the cells penetration into the inner parts and causing the formation of a necrotic core. Furthermore, these structures generally possess a random spatial arrangement and do not preserve the isotropy on the whole volume. Here, we report on the fabrication and testing of an innovative 3D hierarchical, honeycomb-like structure (HS), with reproducible and isotropic arhitecture, that allows in 'volume' migration of osteoblasts. In particular, we demonstrate the possibility to control the 3D spatial cells growth inside these complex architectures by adjusting the free spaces inside the structures. The structures were made of vertical microtubes arranged in a mulitlayered configuration, fabricated via laser direct writing by two photons polymerization of the IP-L780 photopolymer. In vitro tests performed in MG-63 osteoblast-like cells demonstrated that the cells migration inside the 3D structures is conducted by the separation space between the microtubes layers. Specifically, for layers separation between 2 and 10 µm, the cells gradually penetrated between the microtubes. Furthermore, these structures induced the strongest cells osteogenic differentiation and mineralization, with ALP activity 1.5 times stronger, amount of calcified minerals 1.3 times higher and osteocalcin secretion increased by 2.3 times compared to the other structures. On the opposite, for layers separation less than 2 µm and above 10 µm, the cells were not able to make interconnections and exhibited poor mineralization ability.

Treating malignant melanoma when a rare BRAF V600M mutation is present: case report and literature review.

Recent years have brought major advances in the treatment of malignant melanoma. One such an advance is the treatment with BRAF tyrosine-kinase inhibitors in metastatic malignant melanomas that harbor mutations in the BRAF gene. The trials that have been performed in this setting have demonstrated superior response rates and increased overall survival, however, they mostly included patients with melanomas carrying the more common V600E and V600K mutations, not being able to assess the benefit of these treatments in situations where more rare mutations of the BRAF gene are present. We present the evolution of a patient with malignant melanoma with a rare V600M mutation in the BRAF gene, that was eventually treated with vemurafenib. Also we present a brief review of the major phase III trials that showed benefit with tyrosine-kinase inhibitors in BRAF mutated melanoma, with respect to the BRAF mutations included.

Tyrosine-kinase Inhibitors Treatment in Advanced Malignant Melanoma.

OBJECTIVE: To put in perspective recent advances in the treatment of malignant melanoma with novel tyrosine-kinase inhibitors. METHODS: We reviewed the largest trials that support the treatment with tyrosine-kinase inhibitors (TKIs) in cutaneous malignant melanoma, the base of the current guideline recommendations. CONCLUSIONS: Mitogen-activated protein-kinase (MAPK) pathway inhibition via modern TKIs is a major breakthrough in the treatment of melanoma, with a very high benefit for patients with disease harboring BRAF-gene mutations, in terms of rates of response and survival.

Phasic dopamine release in the medial prefrontal cortex enhances stimulus discrimination.

Phasic dopamine (DA) release is believed to guide associative learning. Most studies have focused on projections from the ventral tegmental area (VTA) to the striatum, and the action of DA in other VTA target regions remains unclear. Using optogenetic activation of VTA projections, we examined DA function in the medial prefrontal cortex (mPFC). We found that mice perceived optogenetically induced DA release in mPFC as neither rewarding nor aversive, and did not change their previously learned behavior in response to DA transients. However, repetitive temporal pairing of an auditory conditioned stimulus (CS) with mPFC DA release resulted in faster learning of a subsequent task involving discrimination of the same CS against unpaired stimuli. Similar results were obtained using both appetitive and aversive unconditioned stimuli, supporting the notion that DA transients in mPFC do not represent valence. Using extracellular recordings, we found that CS-DA pairings increased firing of mPFC neurons in response to CSs, and administration of D1 or D2 DA-receptor antagonists in mPFC during learning impaired stimulus discrimination. We conclude that DA transients tune mPFC neurons for the recognition of behaviorally relevant events during learning.

A Toolkit for Orthogonal and in vivo Optical Manipulation of Ionotropic Glutamate Receptors.

The ability to optically manipulate specific neuronal signaling proteins with genetic precision paves the way for the dissection of their roles in brain function, behavior, and disease. Chemical optogenetic control with photoswitchable tethered ligands (PTLs) enables rapid, reversible and reproducible activation or block of specific neurotransmitter-gated receptors and ion channels in specific cells. In this study, we further engineered and characterized the light-activated GluK2 kainate receptor, LiGluR, to develop a toolbox of LiGluR variants. Low-affinity LiGluRs allow for efficient optical control of GluK2 while removing activation by native glutamate, whereas variant RNA edited versions enable the synaptic role of receptors with high and low Ca(2+) permeability to be assessed and spectral variant photoswitches provide flexibility in illumination. Importantly, we establish that LiGluR works efficiently in the cortex of awake, adult mice using standard optogenetic techniques, thus opening the door to probing the role of specific synaptic receptors and cellular signals in the neural circuit operations of the mammalian brain in normal conditions and in disease. The principals developed in this study are widely relevant to the engineering and in vivo use of optically controllable proteins, including other neurotransmitter receptors.