Introduction The general term for non-carious loss of dental tissue (non-carious cervical lesion (NCCL)) is tooth wear which describes the loss of hard dental tissue due to various etiological factors, including chemical and mechanical processes(1). According to Loomans et al., tooth wear, when abnormal for the age of the patient, causes pain and discomfort, functional issues, or decline in aesthetic appearance, and if progressing, may result in complex undesirable complications. Tooth wear can be classified as erosion, abrasion, attrition, and abfraction (2). The clinical observations have shown that the wear mechanisms do not act alone but interact with each other and usually with synergic effect on each other to cause the destruction of dental surfaces(3). The increased occurrence of erosive wear has been reported in young populations due to dietary habits, a growing tendency to consume soft and energy drinks, and the impact of stress. Regardless of the causative factors, tooth wear may affect oral health, personal comfort, loss of vertical dimension of occlusion (VDO), tooth sensitivity, hyperactive muscles, temporomandibular joint problems and pulpal involvement(4). However, aesthetic complaints exist, particularly in young adult patients. The incisal edges may also show signs of wear, shortening due to the loss of enamel support, and subsequent fracture, depending on the progression. A high prevalence of tooth wear has been reported in the young population, which can be reflective of the future dental problems in this generation. Also, in elderly population complete loss of dentition is now second to severe tooth wears as dental problem. For successful treatment of the above cases, paying close attention to the anterior guidance ,posterior contacts and TMJ is essential(5).The significance of anterior guidanceFollowing centric relation (CR), anterior guidance is the most significant factor that must be determined when restoring an occlusion. Aside from its key role in aesthetics, anterior guidance is a crucial factor in protecting the posterior teeth. This protective role of anterior guidance is so important that if the posterior teeth are not protected from lateral and protrusive stresses by the separating effect of the anterior teeth, they will be subjected to high and non-vertical stress over time which can lead to worn dentition. Patient comfort is determined by how accurately the anterior guidance is coordinated with the functional pattern of other parts of masticatory system (6).Posterior-anterior contactsThe following formula should be kept in mind when analyzing the anterior guidance: “Lines in the front and dots in the back. ” The dots in the back merely show the contact points on posterior teeth which means maximum Intercuspation (MI) contacts are coincide with CR. The lines in the front demonstrate the role of anterior teeth in separating the posterior teeth during all eccentric movements. Thus, the stable contacts of anterior teeth in CR and sliding contacts in lateral movements are fundamental issues in extensive restorations (7). This is why this scheme is called “mutually protected system”.Treatment optionsThe biggest problem with restoring worn dentition is there is no space for restorative material to provide optimum resistance and retention form. A variety of treatment options have been proposed, including elective endodontic treatment, surgical crown lengthening for restoration of worn teeth with insufficient restorative space, and prosthetic treatments(8). However, these conventional methods are very costly, time-consuming, and invasive. They destroy a considerable amount of tooth structure and are accounted as an irreversible path for both the patient and dentist. Another problem with these invasive treatment plans is they are heavily dependent on laboratory precision, in fact if dentist has no access to a skillful laboratory whole treatment can lead to a failure. With advances in adhesion and dental bonding agents, minimally invasive restorations have been introduced to preserve the residual tooth structure. More invasive approaches as the treatment options can be postponed until more advanced ages.An alternative treatment option is occlusal veneers which are considered a conservative approach to increase the VDO in cases with severely worn teeth. The durability of these restorations and their ease of construction make them an appropriate conservative treatment option(9). But they are costly and still needs a skillful ceramist.An ultra-conservative and simple treatment is proposed using a combination of composite resin and the Dahl principle to resolve the anterior teeth wear. The Dahl approach involves the creation of inter-occlusal space through axial movement of the teeth via an appliance or the restorations placed in the supra-occlusion and subsequently re-creating the occlusal contacts of the full arch over a time span. The primary Dahl appliance is based on a metal cobalt-chromium appliance cemented on the palatal surfaces of the upper anterior teeth(10). However, the quality and long-term esthetical properties of directly bonded restorations are more dependent on the operator, they have been used recently to create the proper space with low to moderate durability compared to indirect restorations (11). Concerning the directly bonded restorations, as stated by Craig, while using the composites for the restoration of worn teeth is superior to using ceramics due to their lower modulus of elasticity and seemingly satisfactory clinical performance, they require maintenance owing to their limited mechanical and physical properties(12).

Massive circulating metastatic cells: a case of carcinocythemiaCarine Farkh1, Jérome Debus1, Valérie Andrieu1, Juliette Gay11Laboratoire Hématologie, AP-HP, Hôpital Bichat-Claude Bernard, F-75018 Paris, France.

Climate change and shifting environmental conditions can allow pathogens to spread into previously unburdened areas. For plant pathogens, this dynamic has the potential to disrupt natural ecosystem equilibria and human agriculture, making predicting plant pathogen range shifts an increasingly important enterprise. Although such predictions will hinge on an accurate understanding of the determinants of pathogen range – namely the environmental, geographical, and host range characteristics that modulate local pathogen habitation – few studies to date have probed these in natural plant populations. Here, we characterize range determinants for the model system of Lewis flax (Linum Lewisii) and its pathogen, flax rust (Melamspora lini), in the Rocky Mountains. Transect surveys were performed to assess three relationships: i) the effect of geographical features – elevation, slope aspect, slope grade, and land-cover – on flax presence and density, ii) the effect of geographical features on flax rust presence and prevalence, and iii) the effects of flax’s local population density and metapopulation structure on flax rust presence and prevalence. We found that flax population density, but not host metapopulation structure, influences the distribution of flax rust. Additionally, we showed that, while the distribution of flax was broadly constrained to a relatively narrow range of geographical and resulting environmental features, flax rust was evenly distributed across the full range of settings measured. These results indicate that a warming environment, which is expected to modulate such features, may restrict the optimal range of the plant more so than that of its pathogen. Importantly, our results also suggest that even if flax shifts its spatial range to escape increasing climatic pressures, flax rust will not face any significant barriers to track this movement.

Statins as a lipid-lowering drug can selectively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and decrease cholesterol synthesis effectively. With the improvement of nutritional conditions, the demand for statins is increasing in global market. Due to the rapid development of modern biotechnologies, the biosynthesis of stains by microbial cell factory appears great advantages. It has the advantages of simple operation and easy separation of products. This review summarized the strategies on statins production via microbial cell factory, including both traditional fermentation culture and modern synthetic biology manufacture. Firstly, the complex fermentation parameters and process control technology on submerged fermentation (SmF) and solid-state fermentation (SSF) were introduced in detail. Especially, the possibility of recoverable agricultural wastes/(Biomass) as fermentation substrate on solid-state fermentation to produce statins was emphasized. Besides, metabolic engineering strategies to construct robust engineering strains and strains evolution were also discussed. The review highlights the potential and challenge of microbial cell factory to yield the statins. Thus, it will facilitate the production of statins in more green production mode.

A Case of Trichotillomania (TTM) and Bulimia Nervosa (BN) in a Patient with Adult-Onset Attention-Deficit/Hyperactivity Disorder (ADHD)

Imaging findings of succinate dehydrogenase-deficient renal cell carcinoma

The chance for the development of right AFL is strictly related to changes in functional conduction properties of the atrial myocardium which are greatly influenced by fibrotic/scar tissue and increased atrial volume. If these circumstances take place, reduction in conduction velocity can favor a macro-reentry circuit with the wavefront that does not meet its refractory tail and perpetuate the arrhythmia. Therefore, the time required to traverse the entire circuit is related to the circuit’s functional properties. With pacing from the coronary sinus os the right atrial collision time (RACT) of the two wavefronts traveling the circuit in counterclockwise and clockwise direction is calculated. in this prospective study, a cut-off of 115.5 ms of RACT showed a sensitivity and specificity of 92.7% and 93.0% respectively for diagnosis of AFL and an ROC curve indicated an AUC of 0.96 (95% CI: 0.93-1.0, p<0.01). Based on these premises, RACT could be utilized as new marker for the propensity of developing typical AFL.

Gut microbiota andLactobacillus species maintain the small intestine stem cell niche and ameliorate the severity of necrotizing enterocolitis Svabova Tereza1*, Jelinkova Anna1, Gautam Umesh Kumar11Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, 54922 Novy Hradek, Czech Republic.*corresponding author: [email protected] microbiota plays an undisputed role in mammalian development and physiology. It enhances energy extraction from ingested food, protects against harmful pathogens, regulates immune function, and strengthens biochemical signaling. In mammals, including humans, colonization of the gut by microbes begins at birth1, and several recent studies have shown that the microbiome contributes to postnatal host development in early childhood. In this sense, microbial dysbiosis in infancy has been associated with certain diseases such as inflammatory bowel disease, cardiometabolic disorders, cancer, and neuropsychiatric disorders2.The intestinal epithelial cells are in direct contact with a large number of bacteria and the external environment, forming a barrier between inside and outside while fulfilling a critical role in the absorption of nutrients. The small intestine crypt-villus architecture is a unique structure that provides a microenvironment in which intestinal stem cells (ISCs) differentiate into a variety of different epithelial subtypes. These subtypes include enterocytes, also known as intestinal epithelial cells (IECs), Paneth cells, goblet cells, enteroendocrine cells, tuft cells, and microfold cells (M cells)3.Kim et al. demonstrated that early life gut microbiota exposure promotes the differentiation of intestinal stem cells into Paneth cells by regulating numbers of CD206+macrophages associated with epithelial Wnt signaling, which maintains mesenchymal niche cell proliferation (Figure 1). They suggested that the maintenance of this stem cell niche is critical for small intestinal homeostasis and its disruption (e.g., by antibiotic administration) can lead to inflammatory conditions, which can manifest as necrotizing enterocolitis (NEC). NEC is a severe inflammatory disease affecting the small intestine, especially in preterm infants, and is the leading cause of death in this group.To investigate the role of the microbiota and intestinal stem cell differentiation in the pathogenesis of NEC, Kim et al. induced NEC-like phenotypes in neonatal mice by exposing them to hypoxia and gavage feeding of hyperosmolar formula and LPS. ATB-induced dysbiosis resulted in further impaired stem cell niche in the small intestine and led to severe NEC manifestation. They also confirmed previous findings that microbial dysbiosis in NEC is associated with an increased abundance ofProteobacteria and a concomitant underrepresentation ofFirmicutes and Lactobacillus 4. To determine whether members of genus Lactobacillus affect Paneth cell formation during NEC onset, Kim et al. treated pregnant females and their pups with selected Lacticaseibacillus rhamnosus (Lr) strain in the presence or absence of NEC experimental conditions. They found that Lr transplantation corrected the impaired development of the mesenchymal niche and Paneth cell differentiation and consequently partially rescued the NEC-like phenotypes (Figure 1)4.Previous studies in germ-free mice and mice with Toll-like receptor knockout have highlighted the key relationship between the microbiome and NEC development5. Probiotic administration has been suggested as a potential strategy to prevent NEC. In general, probiotic bacteria, including Lactobacillus species, modulate microbiota composition, intestinal epithelial barrier function, and cytokine secretion. Kim et al. showed that transplantation of Lr restored the amount of Lactobacilli resulting in an improvement of NEC-like phenotypes. We have recently shown that administration ofLactiplantibacillus plantarum WJL also increased the proliferation of intestinal epithelial stem cells in chronically undernourished juvenile mice, resulting in improved growth of the young. This effect was strictly bacterial strain-dependent, and NOD2 signaling in intestinal epithelial cells was essential for the bacteria-mediated beneficial effect6. A growing body of evidence suggests that the strain specificity of probiotic microbes and their efficacy in alleviating specific diseases are crucial aspects that are often overlooked when selecting the best probiotic microbes7. Therefore, it would be important to determine whether all probiotic bacterial species or even different Lr strains promote the stem cell niche development by the same mechanism. Further, as it has been shown that NOD2 signaling plays a crucial role in epithelial stem cell proliferation, the role of this receptor in the NEC prevention and development should be probed.To sum up, the study by Kim et al. provides another important contribution to the understanding of the mechanism of NEC pathogenesis. However, more research is needed to fully understand the role ofLactobacilli and other probiotic bacteria in the prevention of NEC and to strengthen their potential as therapeutic agents to combat this serious disease.

Ralstonia solanacearum is a rod-shaped phytopathogenic bacterium that causes lethal wilt disease in many plants. On solid agar growth medium, in the early hour of the growth of the bacterial colony, the type IV pili-mediated twitching motility, which is important for its virulence and biofilm formation, is prominently observed under the microscope. In this study, we have done a detailed observation of twitching motility in R. solanacearum colony. In the beginning, twitching motility in microcolonies was observed as a density-dependent phenomenon that influences the shape and sizes of the microcolonies. No such phenomenon was observed in Escherichia coli, where twitching motility is absent. In the early phase of colony growth, twitching motility exhibited by the cells at the peripheral region of the colony was more prominent than the cells towards the centre of the colony. Using a time scale photography and merging those into a video, twitching motility was observed as an intermittent phenomenon that progresses in layers in all directions as finger-like projections at the peripheral region of a bacterial colony. Each layer of bacteria twitches on top of the other and produces a multi-layered film-like appearance. We found that the duration between the emergence of each layer diminishes progressively as the colony becomes older. This study on twitching motility demonstrates distinctly heterogeneity among the cells within a colony regarding their dynamics and the influence of microcolonies on each other regarding colony shape and size.

Background: There is considerable variation in recommendations from clinical practice guidelines on when and how to screen for glucose intolerance in people with cystic fibrosis (CF). In terms of glucose tolerance, the Australian Standards of Care state that blood glucose monitoring should be performed to exclude hyperglycaemia on a regular basis. Annual oral glucose tolerance test (OGTT) in patients 10 years or older should be considered and performed in patients with symptoms suggestive of glucose impairment or unexplained weight loss, growth failure or worsening respiratory disease.   In 2018, 13 (14%) of the eligible 99 patients with CF ≥10 years old had an OGTT.  Aims: To evaluate the added benefit of enhanced screening to children and adolescents with CF by improving screening to 50% by the end of 2020.  Methods:  A prospective cross-sectional quality improvement cycles was performed on patients in the CF clinic, ≥11 years for OGTT. Patients were excluded from OGTTs if they were prescribed insulin or prolonged oral/parenteral steroids.  Multiple quality improvement initiatives were tried. Each intervention was done as a plan-do-study-act cycles with refinement between each.  Results:  Screening for CF related diabetes (CFRD) increased in 2020 to 60% of >10 year olds. Four patients had new results suggestive of CFRD and ten had new impaired glucose tolerance.  The most successful strategy was sending letters to families.  Conclusion:  The Australian Standards of Care may require revision, as there may be a benefit of routine screening of all children at certain ages as opposed to waiting for symptoms.

The understanding of radiation-induced non-cancer effects on the central nervous system (CNS) is essential for the medical setting (e.g., radiotherapy), and occupational exposures, such as nuclear workers or astronauts. Herein, the adverse outcome pathway (AOP) approach was used to consolidate relevant studies in the area of cognitive decline for identification of research gaps, countermeasure development, and for eventual use in risk assessments. AOPs are an analytical construct describing critical events to an adverse outcome (AO) in a simplified form beginning with a molecular initiating event (MIE). An AOP was constructed utilizing mechanistic information to build empirical support for the key event relationships (KERs) between the MIE of deposition of energy to the AO of learning and memory impairment through multiple key events (KEs). The evidence for the AOP was developed through a scoping review of the literature. In this AOP, the MIE is connected to the AO via six KEs of increased oxidative stress, increased deoxyribonucleic acid (DNA) strand breaks, altered signaling pathways, tissue resident cell activation, increased pro-inflammatory mediators and neural remodeling. Deposition of energy directly leads to oxidative stress, increased DNA strand breaks, an increase of pro-inflammatory mediators and tissue resident cell activation. These KEs, which are themselves interconnected, converge through increased DNA strand breaks, altered signaling pathways and pro-inflammatory routes and directly lead to neural remodeling. Broadly, it is envisioned that the outcome of these efforts could be applied to other cognitive disorders and support ongoing work by international authorities to review the system of radiological protection.

Anthropogenic activities expose many ecosystems to multiple novel disturbances simultaneously. Despite this, how biodiversity responds to simultaneous disturbances remains unclear, with conflicting empirical results on their interactive effects. Here, we experimentally test how one disturbance (an invasive species) affects the diversity of a community over multiple levels of another disturbance regime (pulse mortality). Specifically, we invade stably coexisting bacterial communities under four different pulse frequencies, and compare their final resident diversity to uninvaded communities under the same pulse mortality regimes. Our experiment shows that the disturbances synergistically interact, such that the invader significantly reduces resident diversity at high pulse frequency, but not at low. This work therefore highlights the need to study simultaneous disturbance effects over multiple disturbance regimes as well as to carefully document unmanipulated disturbances, and may help explain the conflicting results seen in previous multiple-disturbance work.

Evaluating the level of green development of cultivated land (GDCL) and its influence mechanism can provide important support for better promoting agricultural green development and rural revitalization. According to the concept of green development, we construct the evaluation system of “adaptability-vitality-resistance (A-V-R)” and explore the spatial and temporal differentiation characteristics and influence mechanism of China’s GDCL in 2000, 2005, 2010, 2015, and 2020 by using the methods of the Comprehensive Evaluation Model, Standard Deviation Ellipse, Theil Index, and Geographic Detector. The results show that: (1) From 2000 to 2020, the level of GDCL in China was low and improved slowly, increasing from 0.264 to 0.293, showing the characteristics of “W” fluctuation, and the focus shifted from Southwest to Northeast. (2) The GDCL in China has obvious spatial dependence, and the evolution of different types of regions has significant path dependence and spatial and temporal inertia. (3) The regional difference in the level of GDCL in China is greater than that among regions. The hierarchical structure characteristics of Northeast Region > Western Region > Central Region > Eastern Region is prominent, and show an overall increasing trend. (4) Human factors greatly impact the level of GDCL. The interaction of driving factors forms a complex multi-resultant force to jointly build a comprehensive action mechanism of GDCL level driven by demand, economy, science and technology, and ecological block.

Staphylococcal scalded skin syndrome (SSSS) in premature infants is a rare condition. We present SSSS in a preterm infant, who developed all signs and symptoms of SSSS at birth, with a fatal outcome due to fungemia caused by Candida parapsilosis. The clinical presentation was challenging to differential diagnosis. SSSS diagnosis was

IntroductionIBD is a chronic systemic inflammatory disease that predominantly involves the gastrointestinal tract. At the same time, it exerts numerous cardiovascular manifestations, like atherosclerotic cardiovascular disease and thromboembolic events, due to a hypercoagulable state. Although the disease mechanism is unclear, factors responsible, like the disruption of the normal coagulation cascade, hyperhomocysteinemia, abnormalities in platelet-endothelial cell interactions, and increased fibrinolysis, are implicated.

Adoptive regulatory T cell (Treg) trasfer represents a potential therapeutic option to control immune responses in organ transplantation, graft vs host disease, and autoimmunity, including type 1 diabetes. Treg for adoptive therapy are traditionally sorted and expanded in vitro with high doses of IL-2, showing stability and suppressive capacity, but with some limitations in terms of long-term survival once infused in patients. Here, we tested a novel expansion protocol in which we added IL-7 (IL-7 method, IL-7M) to the traditional standard method (StM) using IL-2. We showed that naïve Treg express significant levels of CD127 and robustly respond to IL-7 by phosphorylating STAT-5. Naive Treg expanded with the IL-7M were highly enriched in CD45RA +CD62L +CD95 + showing a reduction in the final cell yield and suppressive function. Treg expanded with the IL-7M preserved telomere length and were more resistant to cytokine withdrawal and fas-mediated apoptosis. Overall our data indicate that it is possible to expand naïve Treg in the presence of IL-7 to generate a final Treg product enriched in poorly differentiated CD45RA + cells and with better resistance to stress and apoptosis, potentially improving the long-term survival of Treg in adoptive transfer protocols.

Castleman Disease Presenting as Lymphadenopathy in a Female with Systemic Lupus Erythematosus: A rare case report

The core metabolic reactions of life drive electrons through a class of redox protein enzymes, the oxidoreductases. The energetics of electron flow is determined by the redox potentials of organic and inorganic cofactors as tuned by the protein environment. Understanding how protein structure affects oxidation-reduction energetics is crucial for studying metabolism, creating bioelectronic systems, and tracing the history of biological energy utilization on Earth. We constructed ProtReDox ([https://protein-redox-potential.web.app](https://protein-redox-potential.web.app)), a manually curated database of experimentally determined redox potentials. With over 500 measurements, we can begin to identify how proteins modulate oxidation-reduction energetics across the tree of life. By mapping redox potentials onto networks of oxidoreductase fold evolution, we can infer the evolution of electron transfer energetics over deep-time. ProtReDox is designed to include user-contributed submissions with the intention of making it a valuable resource for researchers in this field.