Loss of epigenetic information as a cause of mammalian aging.

All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.

NKp46 Receptor-Mediated Interferon-γ Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis.

Natural killer (NK) cells are innate lymphoid cells, and their presence within human tumors correlates with better prognosis. However, the mechanisms by which NK cells control tumors in vivo are unclear. Here, we used reflectance confocal microscopy (RCM) imaging in humans and in mice to visualize tumor architecture in vivo. We demonstrated that signaling via the NK cell receptor NKp46 (human) and Ncr1 (mouse) induced interferon-γ (IFN-γ) secretion from intratumoral NK cells. NKp46- and Ncr1-mediated IFN-γ production led to the increased expression of the extracellular matrix protein fibronectin 1 (FN1) in the tumors, which altered primary tumor architecture and resulted in decreased metastases formation. Injection of IFN-γ into tumor-bearing mice or transgenic overexpression of Ncr1 in NK cells in mice resulted in decreased metastasis formation. Thus, we have defined a mechanism of NK cell-mediated control of metastases in vivo that may help develop NK cell-dependent cancer therapies.

Dermoscopic characteristics of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous tumour with high mortality and frequently delayed diagnosis. Clinically, it often manifests as a rapidly growing erythematous to purple nodule usually located on the lower extremities or face and scalp of elderly patients. There is limited available data on the dermoscopic findings of MCC, and there are no specific features that can be used to definitively diagnose MCC. AIM OF THE STUDY: Here, we aimed to summarize existing published literature on dermatoscopic and reflectance confocal microscopy (RCM) features of MCC. MATERIALS AND METHODS: To find relevant studies, we searched the PubMed and Scopus databases from inception to April 12, 2023. Our goal was to identify all pertinent research that had been written in English. The following search strategy was employed: (" dermoscopy" OR " dermatoscopy" OR " videodermoscopy" OR " videodermatoscopy" OR " reflectance confocal microscopy") AND " Merkel cell carcinoma". Two dermatologists, DK and GE, evaluated the titles and abstracts separately for eligibility. For inclusion, only works written in English were taken into account. RESULTS: In total 16 articles were retrieved (68 cases). The main dermoscopic findings of MCC are a polymorphous vascular pattern including linear irregular, arborizing, glomerular, and dotted vessels on a milky red background, with shiny or non-shiny white areas. Pigmentation was lacking in all cases. The RCM images showed a thin and disarranged epidermis, and small hypo-reflective cells that resembled lymphocytes arranged in solid aggregates outlined by fibrous tissue in the dermis. Additionally, there were larger polymorphic hyper-reflective cells that likely represented highly proliferative cells. CONCLUSION: Dermoscopic findings of MCC may play a valuable role in evaluating MCC, aiding in the early detection and differentiation from other skin lesions. Further prospective case-control studies are needed to validate these results.

Melanoma clinicopathological groups characterized and compared with dermoscopy and reflectance confocal microscopy.

BACKGROUND: Dermoscopic and reflectance confocal microscopy (RCM) correlations between morphologic groups of melanoma have not yet been described. OBJECTIVE: Describe and compare dermoscopic and RCM features of cutaneous melanomas with histopathological confirmation. METHODS: Single center, retrospective analysis of consecutive melanomas evaluated with RCM (2015-2019). Lesions were clinically classified as typical, nevus-like, amelanotic/nonmelanoma skin cancer (NMSC)-like, seborrheic keratosis (SK)-like and lentigo/lentigo maligna (LM)-like. Presence or absence of common facial and nonfacial melanoma dermoscopic and RCM patterns were recorded. Clusters were compared with typical lesions by multivariate logistic regression. RESULTS: Among 583 melanoma lesions, significant differences between clusters were evident (compared to typical lesions). Observation of dermoscopic features (>50% of lesions) in amelanotic/NMSC-like lesions consistently displayed 3 patterns (atypical network, atypical vascular pattern + regression structures), and nevus-like and SK-like lesions and lentigo/LM-like lesions consistently displayed 2 patterns (atypical network + regression structures, and nonevident follicles + heavy pigmentation intensity). Differences were less evident with RCM, as almost all lesions were consistent with melanoma diagnosis. LIMITATIONS: Small SK-like lesions sample, single RCM analyses (no reproduction of outcome). CONCLUSION: RCM has the potential to augment our ability to consistently and accurately diagnose melanoma independently of clinical and dermoscopic features.

Line-field confocal optical coherence tomography: Characteristic hints for the diagnosis of scarring alopecia due to lupus erythematodes: A preliminary study.

INTRODUCTION: Lupus erythematosus (LE) is an inflammatory autoimmune disease, that can affect the skin to varying degree. In particular, discoid LE (DLE) and the rare form of lupus panniculitis/profundus are associated with scarring alopecia. The heterogeneity of the clinical, dermatoscopic, and histologic presentation poses a major challenge to the clinician in the diagnosis and differential diagnosis of other forms of scarring alopecia. OBJECTIVE: While noninvasive imaging techniques using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) have proven to be helpful in the diagnosis of scarring alopecia in the context of LE, this study aimed to investigate line-field confocal OCT (LC-OCT) to identify characteristic features of cicatricial alopecia in LE. METHODS: Fifteen patients with cicatricial alopecia in LE were included and the most affected/inflamed areas of the scalp were prospectively examined. In analogy to histopathology and previously reported criteria in RCM, all images were evaluated according to seven established criteria and underwent descriptive analyses. RESULTS: LC-OCT revealed characteristic features of cicatricial alopecia, such as lymphocytic interface dermatitis (14/15; 93.3%) and basal cell vacuolization (13/15; 86.7%). The most impressive feature was the occurrence of prominent hyperreflective fibers in 14/15 patients (93.3%). CONCLUSION: LC-OCT imaging can noninvasively detect morphologic criteria such as lymphocytic and vacuolar interface dermatitis of cicatricial alopecia due to LE. In particular, the presence of hyperreflective collagen fibers appears to be a characteristic easily recognizable feature that may facilitate differential diagnosis with other forms of cicatricial alopecia. Further studies are mandatory to differentiate other forms of scarring alopecia.

Microneedle fractional radiofrequency associated with drug delivery for facial atrophic acne scars and skin rejuvenation.

Microneedle fractional radiofrequency (MFRF) has been used to improve photoaging and scars. This study aimed to evaluate the efficacy and safety of MFRF with basic fibroblast growth factor (bFGF) for facial atrophic acne scars and skin rejuvenation by blinded visual evaluation, self-report, and reflective confocal microscopy (RCM). Fifteen subjects were randomized to the MFRF with bFGF group and fifteen to the MFRF group. All subjects underwent three-session therapy and a follow-up period. Significant group differences were in ECCA, global improvement score, satisfaction, and downtime before and after treatment. Combination therapy could be more effective than monotherapy for acne scars and facial rejuvenation. In addition, RCM can be used to observe the changes in skin collagen before and after treatment in evaluating cosmetic efficacy.

Features of tattoo-associated cutaneous lymphoid hyperplasia on reflectance confocal microscopy and line-field confocal optical coherence tomography.

The popularity of tattoos has led to an increase in associated skin reactions, including complications such as infection, allergic reactions and rare conditions such as tattoo-induced cutaneous lymphoid hyperplasia (CLH). CLH is a benign lymphoproliferative reaction with clinical features resembling malignant cutaneous lymphomas. Non-invasive diagnostic tools like reflectance confocal microscopy (RCM) and the new line-field confocal optical coherence tomography (LC-OCT) are being studied in dermatology better to understand the morphological patterns of many dermatological diseases. Between September 2021 and May 2023, patients with suspicious lesions for tattoo-related CLH were analysed using RCM and LC-OCT before confirming the diagnosis of CLH through skin biopsy and histopathological examination. The study included five cases of CLH. It focused on the analysis of high-quality LC-OCT images/videos and RCM images to investigate the features of CLH in tattooed individuals. Most (80%) cases exhibited a mixed T and B lymphocyte infiltration subtype, while 20% showed a predominant T infiltration subtype. RCM and LC-OCT revealed characteristic features, including architectural disarray, fibrosis, lymphoid infiltrates, and pigment deposits in the epidermis and dermis. Non-invasive tools such as RCM and LC-OCT are valuable in diagnosing tattoo-related CLH. While skin biopsy remains the current standard for diagnosis, RCM and LC-OCT can serve as helpful adjuncts in identifying the most representative area for biopsy. They may potentially become alternative diagnostic options in the future, offering benefits in terms of cost, diagnostic efficiency, aesthetics and patient satisfaction as the prevalence of tattoo-related adverse reactions continues to rise.

A Bicyclic Analog of the Linear Peptide Arodyn Is a Potent and Selective Kappa Opioid Receptor Antagonist.

Kappa opioid receptor (KOR) antagonists have potential therapeutic applications in the treatment of stress-induced relapse to substance abuse and mood disorders. The dynorphin A analog arodyn (Ac[Phe1,2,3,Arg4,D-Ala8]dynorphin A-(1-11)-NH2) exhibits potent and selective kappa opioid receptor antagonism. Multiple cyclizations in longer peptides, such as dynorphin and its analogs, can extend the conformational constraint to additional regions of the peptide beyond what is typically constrained by a single cyclization. Here, we report the design, synthesis, and pharmacological evaluation of a bicyclic arodyn analog with two constraints in the opioid peptide sequence. The peptide, designed based on structure-activity relationships of monocyclic arodyn analogs, was synthesized by solid-phase peptide synthesis and cyclized by sequential ring-closing metathesis (RCM) in the C- and N-terminal sequences. Molecular modeling studies suggest similar interactions of key aromatic and basic residues in the bicyclic peptide with KOR as found in the cryoEM structure of KOR-bound dynorphin, despite substantial differences in the backbone conformations of the two peptides. The bicyclic peptide's affinities at KOR and mu opioid receptors (MOR) were determined in radioligand binding assays, and its KOR antagonism was determined in the [35S]GTPγS assay in KOR-expressing cells. The bicyclic analog retains KOR affinity and selectivity (Ki = 26 nM, 97-fold selectivity over MOR) similar to arodyn and exhibits potent KOR antagonism in the dynorphin-stimulated [35S]GTPγS assay. This bicyclic peptide represents a promising advance in preparing cyclic opioid peptide ligands and opens avenues for the rational design of additional bicyclic opioid peptide analogs.

Dermoscopy and reflectance confocal microscopy-augmented characterization of pigmented micro-basal cell carcinoma (less than 2 mm diameter).

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer, accounting for approximately 80% of nonmelanoma skin cancer diagnoses each year. Among other factors, the staging of BCC is influenced by its measured diameter. Stage 1 BCC is defined as a lesion measuring 2 cm across or less. Of note, there have been increasing publications reporting features of "small-sized" BCCs, which can present smaller than 1 mm. However, few of these studies have characterized features of pigmented small-sized BCC. The application of in-vivo imaging such as dermoscopy and reflectance confocal microscopy (RCM) allows for the non-invasive distinction of these lesions from benign and malignant melanocytic neoplasms, thereby reducing unnecessary biopsies. METHODS: Within one year, three patients presented to Oregon Health and Science University's dermatology clinic with pigmented lesions of concern measuring less than 2 mm that were histologically confirmed as pigmented BCC. We sought to characterize the features of these lesions in a case series with the non-invasive imaging modalities of dermoscopy and RCM. RESULTS: All cases presented clinically as a small, brown, macule on the face. Each of the three cases exhibited differing features on dermoscopy. With the application of RCM, we were able to visualize characteristic BCC features, prompting removal by shave biopsy. CONCLUSION: To our knowledge, no other study has reported dermoscopic and RCM features of a cohort of pigmented BCCs 2 mm in diameter or smaller. We propose to define BCCs of this size as micro-BCCs. The variability of dermoscopic findings observed in our study, combined with the small size of these pigmented lesions, shows the utility of RCM as a non-invasive diagnostic tool for pigmented micro-BCCs.

Reflectance confocal microscopic visualization of melanocytic bodies in the stratum corneum overlying acral lentiginous melanoma.

BACKGROUND: We present a case of RCM evaluation of ALM surgical margins demonstrating intracorneal melanocytic bodies overlying subsequently confirmed melanoma in situ by histopathology. CASE PRESENTATION: A 73-year-old male with a history of acral lentiginous melanoma (ALM) of the right great toe presented to our clinic for evaluation of positive surgical margins. The positive margin was localized for examination and subsequent biopsy with reflectance confocal microscopy (RCM) which allowed targeted re-resection of the area of concern. Three punch biopsies were obtained in the area of concern, which confirmed residual melanoma in situ. Immunostains confirmed the cellular remnants in the stratum corneum were melanocytic. To correlate the intra stratum corneum findings seen with confocal to the histopathology, a 3D rendering of a stack of images was used to demonstrate the location. DISCUSSION: Typically, acral surfaces are challenging to examine with RCM due to the limited ability of light to penetrate thickened stratum corneum; however, we observed unique cellular features with confocal. Scattered hyper-reflective pleomorphic cells consistent with melanocytes were observed in the stratum corneum, although the visualized underlying epidermis appeared normal. Confocal microscopy may aid in diagnosis and management of ALM, especially in the context of positive surgical margins.

Restrictive cardiomyopathy: definition and diagnosis.

Restrictive cardiomyopathy (RCM) is a heterogeneous group of diseases characterized by restrictive left ventricular pathophysiology, i.e. a rapid rise in ventricular pressure with only small increases in filling volume due to increased myocardial stiffness. More precisely, the defining feature of RCM is the coexistence of persistent restrictive pathophysiology, diastolic dysfunction, non-dilated ventricles, and atrial dilatation, regardless of ventricular wall thickness and systolic function. Beyond this shared haemodynamic hallmark, the phenotypic spectrum of RCM is wide. The disorders manifesting as RCM may be classified according to four main disease mechanisms: (i) interstitial fibrosis and intrinsic myocardial dysfunction, (ii) infiltration of extracellular spaces, (iii) accumulation of storage material within cardiomyocytes, or (iv) endomyocardial fibrosis. Many disorders do not show restrictive pathophysiology throughout their natural history, but only at an initial stage (with an evolution towards a hypokinetic and dilated phenotype) or at a terminal stage (often progressing from a hypertrophic phenotype). Furthermore, elements of both hypertrophic and restrictive phenotypes may coexist in some patients, making the classification challenge. Restrictive pathophysiology can be demonstrated by cardiac catheterization or Doppler echocardiography. The specific conditions may usually be diagnosed based on clinical data, 12-lead electrocardiogram, echocardiography, nuclear medicine, or cardiovascular magnetic resonance, but further investigations may be needed, up to endomyocardial biopsy and genetic evaluation. The spectrum of therapies is also wide and heterogeneous, but disease-modifying treatments are available only for cardiac amyloidosis and, partially, for iron overload cardiomyopathy.

Influence of Substituents in a Six-Membered Chelate Ring of HG-Type Complexes Containing an N→Ru Bond on Their Stability and Catalytic Activity.

An efficient approach to the synthesis of olefin metathesis HG-type catalysts containing an N→Ru bond in a six-membered chelate ring was proposed. For the most part, these ruthenium chelates can be prepared easily and in high yields based on the interaction between 2-vinylbenzylamines and Ind II (the common precursor for Ru-complex synthesis). It was demonstrated that the increase of the steric volume of substituents attached to the nitrogen atom and in the α-position of the benzylidene fragment leads to a dramatic decrease in the stability of the target ruthenium complexes. The bulkiest iPr substituent bonded to the nitrogen atom or to the α-position does not allow the closing of the chelate cycle. N,N-Diethyl-1-(2-vinylphenyl)propan-1-amine is a limiting case; its interaction with Ind II makes it possible to isolate the corresponding ruthenium chelate in a low yield (5%). Catalytic activity of the synthesized complexes was tested in RCM reactions and compared with α-unsubstituted catalysts obtained previously. The structural peculiarities of the final ruthenium complexes were thoroughly investigated using XRD and NMR analysis, which allowed making a reliable correlation between the structure of the complexes and their catalytic properties.

Performance evaluation of multiple regional climate models to simulate rainfall in the Central Rift Valley Lakes Basin of Ethiopia and their selection criteria for the best climate model.

The historical datasets of five regional climate models (RCMs) available in the Coordinated Regional Downscaling Experiment (CORDEX)-Africa database are evaluated against ground-based observed rainfall in the Central Rift Valley Lakes Basin of Ethiopia. The evaluation is aimed at determining how well the RCMs reproduce monthly, seasonal, and annual cycles of rainfall and quantify the uncertainty between the RCMs in downscaling the same global climate model outputs. Root mean square, bias, and correlation coefficient are used to evaluate the ability of the RCM output. The multicriteria decision method of compromise programming was used to choose the best climate models for the climate condition of the Central Rift Valley Lakes subbasin. The Rossby Center Regional Atmospheric Model (RCA4) has downscaled ten global climate models (GCMs) and reproduces the monthly rainfall with a complex spatial distribution of bias and root mean square errors. The monthly bias varies in the range of - 35.8 to 189%. The summer (wet), spring, winter (dry), and annual rainfall varied within the range of 1.44 to 23.66%, - 7.08 to 20.04%, - 7.35 to 57%, and - 3.11 to 16.5%, respectively. To find the source of uncertainty, the same GCMs but downscaled by different RCMs were analyzed. The test results showed that each RCM differently downscaled the same GCM, and there was no single RCM model that consistently simulated the climate conditions over the stations in the study regions. However, the evaluation finds reasonable model skill in representing the temporal cycles of rainfall and suggests the use of RCMs where climate data is scarce after bias correction.

Molecular Dynamic Simulation Analysis of a Novel Missense Variant in CYB5R3 Gene in Patients with Methemoglobinemia.

Background and Objective: Mutations in the CYB5R3 gene cause reduced NADH-dependent cytochrome b5 reductase enzyme function and consequently lead to recessive congenital methemoglobinemia (RCM). RCM exists as RCM type I (RCM1) and RCM type II (RCM2). RCM1 leads to higher methemoglobin levels causing only cyanosis, while in RCM2, neurological complications are also present along with cyanosis. Materials and Methods: In the current study, a consanguineous Pakistani family with three individuals showing clinical manifestations of cyanosis, chest pain radiating to the left arm, dyspnea, orthopnea, and hemoptysis was studied. Following clinical assessment, a search for the causative gene was performed using whole exome sequencing (WES) and Sanger sequencing. Various variant effect prediction tools and ACMG criteria were applied to interpret the pathogenicity of the prioritized variants. Molecular dynamic simulation studies of wild and mutant systems were performed to determine the stability of the mutant CYB5R3 protein. Results: Data analysis of WES revealed a novel homozygous missense variant NM_001171660.2: c.670A > T: NP_001165131.1: p.(Ile224Phe) in exon 8 of the CYB5R3 gene located on chromosome 22q13.2. Sanger sequencing validated the segregation of the identified variant with the disease phenotype within the family. Bioinformatics prediction tools and ACMG guidelines predicted the identified variant p.(Ile224Phe) as disease-causing and likely pathogenic, respectively. Molecular dynamics study revealed that the variant p.(Ile224Phe) in the CYB5R3 resides in the NADH domain of the protein, the aberrant function of which is detrimental. Conclusions: The present study expanded the variant spectrum of the CYB5R3 gene. This will facilitate genetic counselling of the same and other similar families carrying mutations in the CYB5R3 gene.

A NOVEL AND HYBRID WHALE OPTIMIZATION WITH RESTRICTED CROSSOVER AND MUTATION BASED FEATURE SELECTION METHOD FOR ANXIETY AND DEPRESSION.

BACKGROUND: Anxiety and depression are two leading human psychological disorders. In this work, several swarm intelligence-based metaheuristic techniques have been employed to find an optimal feature set for the diagnosis of these two human psychological disorders. SUBJECTS AND METHODS: To diagnose depression and anxiety among people, a random dataset comprising 1128 instances and 46 attributes has been considered and examined. The dataset was collected and compiled manually by visiting the number of clinics situated in different cities of Haryana (one of the states of India). Afterwards, nine emerging meta-heuristic techniques (Genetic algorithm, binary Grey Wolf Optimizer, Ant Colony Optimization, Particle Swarm Optimization, Artificial Bee Colony, Firefly Algorithm, Dragonfly Algorithm, Bat Algorithm and Whale Optimization Algorithm) have been employed to find the optimal feature set used to diagnose depression and anxiety among humans. To avoid local optima and to maintain the balance between exploration and exploitation, a new hybrid feature selection technique called Restricted Crossover Mutation based Whale Optimization Algorithm (RCM-WOA) has been designed. RESULTS: The swarm intelligence-based meta-heuristic algorithms have been applied to the datasets. The performance of these algorithms has been evaluated using different performance metrics such as accuracy, sensitivity, specificity, precision, recall, f-measure, error rate, execution time and convergence curve. The rate of accuracy reached utilizing the proposed method RCM-WOA is 91.4%. CONCLUSION: Depression and Anxiety are two critical psychological disorders that may lead to other chronic and life-threatening human disorders. The proposed algorithm (RCM-WOA) was found to be more suitable compared to the other state of art methods.

Three novel mutations in CYB5R3 gene causing NADH-cytochrome b5 reductase enzyme deficiency leads to recessive congenital methaemoglobinemia.

BACKGROUND: Methemoglobin is the reduced form of haemoglobin that is normally found in the blood in levels < 1%. Methemoglobinemia can occur as a congenital or acquired disease. Two types of recessive congenital methaemoglobinemia (RCM) are caused by the NADH-dependent cytochrome b5 reductase enzyme deficiency of the CYB5R3 gene. RCM-I is characterized by higher methaemoglobin levels (> 2 g/dL), causing only cyanosis, whereas RCM-II is associated with cyanosis with neurological impairment. METHODS: Routine haematological investigations were done by standard method. The methaemoglobin level was evaluated by the potassium ferricyanide assay. NADH-cytochrome b5 reductase (cytb5r) enzyme activities were measured by standard methods, and molecular analysis was performed by polymerase chain reaction (PCR) followed by DNA sequencing. The interpretation of mutation effect and the molecular modeling were performed by using specific software DEEP VIEW SWISS-PDB VIEWER and Pymol molecular graphics program. RESULTS: The present study discovered three novel homozygous pathogenic variants of CYB5R3 causing RCM I and II in four unrelated Indian patients. In patient-1 and patient-2 of RCM type I caused due to novel c.175C>T (p.Arg59Cys) and other reported c.469T>C (p.Phe157Ser) missense pathogenic variants respectively, whereas patient-3 and patient-4 presented with the RCM type II are related to developmental delay with cyanosis since birth due to a novel homozygous (g.25679_25679delA) splice-site deletion and novel homozygous c.824_825insC (p.Pro278ThrfsTer367) single nucleotide insertion. The CYB5R3 transcript levels were estimated by qRT-PCR in the splice-site deletion, which was 0.33fold of normal healthy control. The insertion of nucleotide C resulted in a frameshift of termination codon are associated with neurological impairment. CONCLUSIONS: Molecular diagnosis of RCM can help to conduct genetic counselling for novel mutations and, subsequently, prenatal diagnosis of high-risk genetic disorders.

Improving dermal level images from reflectance confocal microscopy using wavelet-based transformations and adaptive histogram equalization.

OBJECTIVES: Reflectance confocal microscopy (RCM) generates scalar image data from serial depths in the skin, allowing in vivo examination of cellular features. The maximum imaging depth of RCM is approximately 250 µm, to the papillary dermis, or upper reticular dermis. Frequently, important diagnostic features are present in the dermis, hence improved visualization of deeper levels is advantageous. METHODS: Low contrast and noise in dermal images were improved by employing a combination of wavelet-based transformations and contrast-limited adaptive histogram equalization. RESULTS: Preserved details, noise reduction, increased contrast, and feature enhancement were observed in the resulting processed images. CONCLUSIONS: Complex and combined wavelet-based enhancement approaches for dermal level images yielded reconstructions of higher quality than less sophisticated histogram-based strategies. Image optimization may improve the diagnostic accuracy of RCM, especially for entities with dermal findings.

A New Robotic Endoscope Holder for Ear and Sinus Surgery with an Integrated Safety Device.

In the field of sinus and ear surgery, and more generally in microsurgery, the surgeon is faced with several challenges. The operations are traditionally carried out under binocular loupes, which allows for the surgeon to use both hands for a microinstrument and an aspiration tool. More recently, the development of endoscopic otological surgery allowed for seeing areas that are difficult to access. However, the need to handle the endoscope reduces the surgeon's ability to use only one instrument at a time. Thus, despite anaesthesia, patient motions during surgery can be very risky and are not that rare. Because the insertion zone in the middle ear or in the sinus cavity is very small, the mobility of the endoscope is limited to a rotation around a virtual point and a translation for the insertion of the camera. A mechanism with remote center motion (RCM) is a good candidate to achieve this movement and allow for the surgeon to access the ear or sinus. Since only the translational motion along the main insertion axis is enabled, the ejection motion along the same axis is safe for the patient. A specific mechanism allows for inserting and ejecting the endoscope. In a sense, the position is controlled, and the velocity is limited. In the opposite sense, the energy stored in the spring allows for very quick ejection if the patient moves. A prototype robot is presented using these new concepts. Commercially available components are used to enable initial tests to be carried out on synthetic bones to validate the mobility of the robot and its safety functions.

Specifying Inputs for the Computational Structure of a Surgical System via Optical Method and DLT Algorithm Based on In Vitro Experiments on Cardiovascular Tissue in Minimally Invasive and Robotic Surgery.

With the application of four optical CMOS sensors, it was possible to capture the trajectory of an endoscopic tool during an in vitro surgical experiment on a cardiovascular preparation. This was due to the possibility of obtaining a path when a reflective marker was attached. In the work, APAS (Ariel Performance Analysis System) software and DLT (direct linear transformation) algorithm were used. This made it possible to acquire kinematic inputs to the computational model of dynamics, which enabled, regardless of the type of surgical robot structure, derivation of the analogous motion of an endoscopic effector due to the mathematical transformation of the trajectory to joints coordinates. Experiments were carried out with the participation of a practiced cardiac surgeon employing classic endoscopic instruments and robot surgical systems. The results indicated by the experiment showed that the inverse task of kinematics of position for the surgical robot with RCM (remote center of motion) structure was solved. The achieved results from the experiment were used as inputs for deriving a numerical dynamics model of surgical robot during transient states that was obtained by applying the finite element method and by driving dynamics moments acquired through the block diagrams method using a steering system with DC (direct current) motor and PID (proportional-integral-derivative) controller. The results section illustrates the course of kinematic values of endoscopic tools which were employed to apply numerical models as inputs, the course of the driving torque of the model of the surgical robot that enabled the selection of the drive system and the strength values, stresses and displacements according to von Mises hypothesis in its structure during the analysis of transient states that made it possible to establish the strength safety of the surgical robot. For the conducted experiments, the accuracy was ±2 [mm]. In the paper, the employment of optical CMOS sensors in surgical robotics and endoscopy is discussed. The paper concludes that the usage of optical sensors for determining inputs for numerical models of dynamics of surgical robots provides the basis for setting the course of physical quantities that appear in their real object structure, in manners close to reality.

Ring-Opening Metathesis Polymerization and Related Olefin Metathesis Reactions in Benzotrifluoride as an Environmentally Advantageous Medium.

A tremendous number of solvents, either as liquids or vapors, contaminate the environment on a daily basis worldwide. Olefin metathesis, which has been widely used as high-yielding protocols for ring-opening metathesis polymerization (ROMP), ring-closing metathesis (RCM), and isomerization reactions, is typically performed in toxic and volatile solvents such as dichloromethane. In this study, the results of our systematic experiments with the Grubbs G1, G2, and Hoveyda-Grubbs HG2 catalysts proved that benzotrifluoride (BTF) can replace dichloromethane (DCM) in these reactions, providing high yields and similar or even higher reaction rates in certain cases. The ROMP of norbornene resulted not only in high yields but also in polynorbornenes with a high molecular weight at low catalyst loadings. Ring-closing metathesis (RCM) experiments proved that, with the exception of the G1 catalyst, RCM occurs with similar high efficiencies in BTF as in DCM. It was found that isomerization of (Z)-but-2-ene-1,4-diyl diacetate with the G2 and HG2 catalysts proceeds at significantly higher initial rates in BTF than in DCM, leading to rapid isomerization with high yields in a short time. Overall, BTF is a suitable solvent for olefin metathesis, such as polymer syntheses by ROMP and the ring-closing and isomerization reactions.