Platelet mechanosensing as key to understanding platelet function.

PURPOSE OF REVIEW: This review highlights how the perception of platelet function is evolving based on recent insights into platelet mechanobiology. RECENT FINDINGS: The mechanosensitive ion channel Piezo1 mediates activation of free-flowing platelets under conditions of flow acceleration through mechanisms independent of adhesion receptors and classical activation pathways. Interference with the initiation of platelet migration or with the phenotypic switch of migrating platelets to a procoagulant state aggravates inflammatory bleeding. Mechanosensing of biochemical and biophysical microenvironmental cues during thrombus formation feed into platelet contractile force generation. Measurements of single platelet contraction and bulk clot retraction show promise to identify individuals at risk for hemorrhage. SUMMARY: New findings unravel novel mechanotransduction pathways and effector functions in platelets, establishing mechanobiology as a pivotal component of platelet function. These insights highlight limitations of existing treatments and offer new potential therapeutic approaches and diagnostic avenues based on mechanobiological principles. Further extensive research is required to distinguish between core hemostatic and pathological mechanisms influenced by platelet mechanosensing.

Environmental tobacco smoke and children's health: a bibliometric and altmetric analysis of 100 most cited articles.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is arguably the most ubiquitous and hazardous, even at very low levels, starting in early life. The objective of this study was to describe the state of research and future trends on ETS exposure and Children's Health (CH) topics with bibliometrics and altmetrics. METHODS: An electronic search was performed in Scopus database on January 31, 2023. Consensus was arrived on 100 most-cited articles by two reviewers. These papers were then cross matched with citations harvested from Web of Science (WoS) and Google Scholar. Altmetric Attention Score (AAS) and Dimension counts were also collected. Analysis and network visualization of authors, countries, and keywords were generated using VOSviewer software. RESULTS: Among a total of 1107 articles published on ETS and CH, the 100 top-cited articles appeared in 54 journals, with Pediatrics (n = 12) contributing a maximum number of articles. The time period between 2000 and 2009 accounted for 44% of all publications. With respect to the research design employed across these studies, cross-sectional design took precedence over others accounting for approximately 40%. Predominantly, articles focused on childhood asthma; however, current research trends have shifted towards emerging fields such as children's oral health and DNA methylation. Twitter, policy documents, and news outlets were the main platforms where outputs were discussed. The AAS was not associated with journal impact factor or access type. Weak correlations were observed between AAS and citation count in Scopus, WoS, and Google Scholar (r = 0.17 to 0.27) while a positive association existed between dimension count and the number of citations across all three databases (r = 0.84 to 0.98). CONCLUSION: This study demonstrates the evolution, digital dissemination and research hotspots in the field of ETS and CH, predicting the possible future research directions. High-quality studies with more specific exposure classification are warranted to better understand the relationship between ETS and CH.

Year-round sustainable biomass production potential of Nannochloris sp. in outdoor raceway pond enabled through strategic photobiological screening.

Microalgae cultivation utilizes the energy of sunlight to reduce carbon dioxide (CO2) for producing renewable energy feedstock. The commercial success of the biological fixation of carbon in a consistent manner depends upon the availability of a robust microalgae strain. In the present work, we report the identification of a novel marine Nannochloris sp. through multiparametric photosynthetic evaluation. Detailed photobiological analysis of this strain has revealed a smaller functional antenna, faster relaxation kinetics of non-photochemical quenching, and a high photosynthetic rate with increasing light and temperatures. Furthermore, laboratory scale growth assessment demonstrated a broad range halotolerance of 10-70 parts per thousand (PPT) and high-temperature tolerance up to 45 °C. Such traits led to the translation of biomass productivity potential from the laboratory scale (0.2-3.0 L) to the outdoor 50,000 L raceway pond scale (500-m2) without any pond crashes. The current investigation revealed outdoor single-day peak areal biomass productivity of 43 g m-2 d-1 in summer with an annual (March 2019-February 2020) average productivity of 20 g m-2 d-1 in seawater. From a sustainability perspective, this is the first report of successful round-the-year (> 347 days) multi-season (summer, monsoon, and winter) outdoor cultivation of Nannochloris sp. in broad seawater salinity (1-57 PPT), wide temperature ranges (15-40 °C), and in fluctuating light conditions. Concurrently, outdoor cultivation of this strain demonstrated conducive fatty acid distribution, including increased unsaturated fatty acids in winter. This inherent characteristic might play a role in protecting photosynthesis machinery at low temperatures and in high light stress. Altogether, our marine Nannochloris sp. showed tremendous potential for commercial scale cultivation to produce biofuels, food ingredients, and a sustainable source for vegetarian protein.

Efficacy of Infrazygomatic Crest Implants for Full-arch Distalization of Maxilla and Reduction of Gummy Smile in Class II Malocclusion.

AIM: The purpose of the study was to evaluate the efficacy of infrazygomatic (IZ) implants along with mini-implants for full-arch distalization of maxilla and reduction of gummy smile in patients with class II division I malocclusion. MATERIALS AND METHODS: Ten orthodontic patients were taken from the department of orthodontics and dentofacial orthopedics. Each patient required distalization and intrusion of the complete maxillary arch as a part of the treatment plan. Patients were of class II malocclusion with gummy smile. Initial leveling and alignment were done by using 0.22″ slot Mclaughlin Bennett Trevisi (MBT) prescription. Fav Anchor infrazygomatic crest (IZC) implants of 2 mm of head diameter and 14 mm length were inserted between first and second molar and 2 mm above the mucogingival junction in the alveolar mucosa and in the anterior region, two titanium mini-implants of 1.4 mm head diameter and 6 mm length. The screws were loaded immediately with e-chain with a minimal force from mini-implants in the anterior region to crimpable hook placed between lateral and canine and continuing the same till the IZ implants. To measure the amount of distalization and reduction of gummy smile, pre- and postlateral cephalograms were taken and assessed. Pre- and postdistalization and intrusion readings of all patients were obtained and calculated statistically for quantifying the amount of distalization of maxillary arch and intrusion for reduction of gummy smile. RESULTS: The distalization of the maxillary arch achieved was 4.6 mm which is clinically and statistically significant. The anterior teeth in the study were intruded with a minimum of 3.8 mm which is clinically and statistically significant; the gingival smile line was reduced with a mean of 3.4 mm which is clinically and statistically significant. Overbite correction of 4 mm was done with the mean difference of 4 mm which is also statistically significant. CONCLUSION: The IZ bone screws can be effectively used as an absolute anchorage to correct class II skeletal discrepancy with gummy smile devoid of premolar extraction with noninvasive procedure. CLINICAL SIGNIFICANCE: The use of IZC implants along with anterior implants, a biomechanical approach is effective in achieving full-arch distalization of maxilla and intrusion as the force vectors allow that the line of action passes through the center of resistance (Cr) of the entire maxillary arch, facilitates the distalization and intrusion of the maxillary arch, establishes ideal occlusion, and improves the smile esthetics.

Assessment of Correlation between Craniofacial Proportions and Genetic Indicators.

AIM AND OBJECTIVE: To assess correlation among craniofacial proportions and genetic indicators using estrogen receptors (ESR1 and ESR2). MATERIALS AND METHODS: A total of 128 patients undergoing orthodontic treatment with age range 12-18 years of both genders were included. Lateral cephalogram of all subjects were taken. Vertical and sagittal parameters were studied on these cephalogram. Saliva was used for DNA extraction. Real-time polymerase chain reaction was performed for assessment of genetic indicators in ESR1 (rs9340799 and rs2234693) and in ESR2 (rs4986938 and rs1256049). RESULTS: The mean SN cranial base was 68.4 mm, ANB (sagittal jaw relationship) was 2.8°, Ptm-A maxillary length was 46.2 mm, Go-Pg (mandibular body length) was 68.2 mm, Co-Gn (total mandibular length) was 112.8 mm, lower anterior facial height (ANS-Me) was 58.4 mm, N-Me (total anterior facial height) was 108.4 mm, lower posterior facial height (Co-Go) was 58.7 mm, and S-Go (total posterior facial height) was 72.4 mm. It was found that rs4986938 in ESR2 was linked with S-N dimension, with patients having CC genotype possessing negative correlation values (p value 0.05). Similarly, CC genotype possessed minimum mandibular body dimension, and it was found that rs4986938 in ESR2 was also linked with Go-Pg dimension (p value = 0.02). We found reduction in the ANS-Me values in patients with CC genotype in ESR1 rs2234693 (p value = 0.02), whereas there was no correlation of rest genotype with other craniofacial measurements (p value > 0.05). CONCLUSION: Evaluation of ESR1 and ESR2 may show role of genetic markers in disparity of craniofacial dimensions in individuals. CLINICAL SIGNIFICANCE: This study provides an outlay and supports the concept of possible correlation between genetic markers and craniofacial measurements.

Membrane-initiated estrogen signaling in prostate cancer: A route to epithelial-to-mesenchymal transition.

The plasma membrane (PM) is considered as a major druggable site. More than 50% of the existing drugs target PM proteins. In the wake of emerging data indicating a key role of estrogens in prostate cancer (PCa) pathogenesis, the study was undertaken to explore whether the estrogen binding sites exist on the PM and if such sites are functionally relevant in PCa. Estradiol (E2) binding to the PM was detected in androgen-dependent (LNCaP), androgen-independent (PC3, DU145) PCa cell lines, nontumorigenic (RWPE1) prostate epithelial cell line, and rat prostate cells. Conventional estrogen receptors (nuclear estrogen receptors), known for their nuclear localization, were detected in the PM enriched extracts. This was indirectly confirmed by reduced localization of ERs on the PM of cells, silenced for the expression of their cognate genes. Further, unlike cell-permeable E2, stimulation with cell-impermeable estradiol (E2-BSA) did not induce proliferation in LNCaP cells. However, stimulation with E2-BSA led to alterations in the phosphorylation status of several kinases including GSK3 and AKT, along with the hyperphosphorylation of cytoskeletal proteins such as ß-actin and cytokeratin 8 in LNCaP. This was accompanied by epithelial-to-mesenchymal (EMT) features such as increased migration and invasion; higher vimentin expression, and a concomitant decrease in the E-cadherin expression. These effects were not observed in RWPE1 cells. Interestingly, cell-permeable E2 failed to induce EMT in PCa cells. This in vitro study is the first to suggest that the PM-initiated estrogen signaling contributes to higher invasiveness in PCa cells. Plasma membrane ERs may act as novel targets for PCa therapeutics.

Modulation in light utilization by a microalga Asteracys sp. under mixotrophic growth regimes.

This study is the first to explore the influence of incident light intensity on the photosynthetic responses under mixotrophic growth of microalga Asteracys sp. When grown mixotrophically, there was an enhanced regulation of non-photochemical quenching (NPQ) of the excited state of chlorophyll (Chl) a within the cells in response to white cool fluorescent high light (HL; 600 µmol photons m-2 s-1). Simultaneous measurement of reactive oxygen species (ROS) production as malondialdehyde (MDA) and ascorbate peroxidase (APX), an ROS scavenger, showed improved management of stress within mixotrophic cells under HL. Despite the observed decrease in quantum yield of photosynthesis measured through the Chl a fluorescence transient, no reduction in biomass accumulation was observed under HL for mixotrophy. However, biomass loss owing to photoinhibition was observed in cells grown phototrophically under the same irradiance. The measurements of dark recovery of NPQ suggested that "state transitions" may be partly responsible for regulating overall photosynthesis in Asteracys sp. The partitioning of photochemical and non-photochemical processes to sustain HL stress was analysed. Collectively, this study proposes that mixotrophy using glucose leads to a change in the photosynthetic abilities of Asteracys sp. while enhancing the adaptability of the alga to high irradiances.

Influence of nitrogen source on photochemistry and antenna size of the photosystems in marine green macroalgae, Ulva lactuca.

Ulva lactuca is regarded as a prospective energy crop for biorefinery owing to its affluent biochemical composition and high growth rate. In fast-growing macroalgae, biomass development strictly depends on external nitrogen pools. Additionally, nitrogen uptake rates and photosynthetic pigment content vary with type of nitrogen source and light conditions. However, the combined influence of nitrogen source and light intensity on photosynthesis is not widely studied. In present study, pale green phenotype of U. lactuca was obtained under high light (HL) condition when inorganic nitrogen (nitrate) in the media was substituted with organic nitrogen (urea). Further, pale green phenotype survived the saturating light intensities in contrast to the normal pigmented control which bleached in HL. Detailed analysis of biochemical composition and photosynthesis was performed to understand functional antenna size and photoprotection in pale green phenotype. Under HL, urea-grown cultures exhibited increased growth rate, carbohydrate and lipid content while substantial reduction in protein, chlorophyll content and PSII antenna size was observed. Further, in vivo slow and polyphasic chlorophyll a (Chl a) fluorescence studies revealed reduction in excitation pressure on PSII along with low non-photochemical quenching thus, transmitting most of the absorbed energy into photochemistry. The results obtained could be correlated to previous report on cultivation of U. lactuca through saturating summer intensities (1000 µmole photons m-2 s-1) in urea based: poultry litter extract (PLE). Having proved critical role of urea in conforming photoprotection, the application PLE was authenticated for futuristic, sustainable and year-round biomass cultivation.

Modified Activation Technique for Nasal Stent of Nasoalveolar Molding Appliance for Columellar Lengthening in Bilateral Cleft Lip/Palate.

Bilateral cleft lip/cleft palate is associated with nasal deformities typified by a short columella. The presurgical nasoalveolar molding (NAM) therapy approach includes reduction of the size of the intraoral alveolar cleft as well as positioning of the surrounding deformed soft tissues and cartilages. In a bilateral cleft patient, NAM, along with columellar elongation, eliminates the need for columellar lengthening surgery. Thus the frequent surgical intervention to achieve the desired esthetic results can be avoided. This article proposes a modified activation technique of the nasal stent for a NAM appliance for columellar lengthening in bilateral cleft lip/palate patients. The design highlights relining of the columellar portion of the nasal stent and the wire-bending of the nasal stent to achieve desirable results within the limited span of plasticity of the nasal cartilages. With this technique the vertical taping of the premaxilla to the oral plate can be avoided.

Simple Technique to Reorient Different Casts of Same Patient on a Dental Surveyor.

Accurate planning for the framework design of removable partial dentures requires careful analysis of the diagnostic cast with a dental surveyor to determine the optimal path of placement. Some techniques described in the literature are helpful in reorienting the same cast on the surveyor, including the tripod marking method; however, there is a possibility of introducing human errors during marking and repositioning of the tripod points on to the different casts at the same location. Other techniques, which do not require markings on the cast to reorient different casts of the same patient, need specific devices or trays. This article suggests the direct use of a putty-elastomeric orientation index that can be preserved and used multiple times while reorienting different casts of the same patients at various laboratory steps. A putty elastomeric impression material is mixed and adapted on to the diagnostic cast, covering key teeth areas of the cast and incorporating the analyzing rod of the surveyor. Thus there is no need to use a special device or the tray to reorient different casts.

Two-Colored Dental Surveying Tool as an Alternative for Carbon Marker.

Various tools are used with a dental surveyor, including analyzing rods, carbon markers, undercut gauges, and protective sheaths for a specific function. A carbon marker is a parallel-sided carbon rod used to mark the survey line on a cast or a crown on a cast. The carbon marker (with or without protective sheath) cannot differentiate more than one survey line on the cast if needed. The wear of the carbon marker along the parallel walls after repeated use may give an incorrect survey line. We suggest a simple modification in the analyzing rod to prepare a two-colored surveying tool. An analyzing rod is a parallel-sided rod used to analyze the relative parallelism of two or more surfaces of a cast and to mark survey lines on wax patterns. With the modified analyzing rod, the survey lines can be marked with two colors, and the problem of breaking of the carbon marker also can be eliminated.

Lost wax-bolus technique to process closed hollow obturator with uniform wall thickness using single flasking procedure.

INTRODUCTION: Maxillary obturator prosthesis is more frequent treatment modality than surgical reconstruction for maxillectomy in patients suffering from oral cancer. The obturators often become heavy and hence are hollowed out in the defect portion to reduce its weight as a standard practice. MATERIALS AND METHODS: The processing technique described the incorporation of the preshaped "wax-bolus" during packing procedure of the Obturtor prosthesis and eliminated later by melting it once the curing procedure is completed. RESULTS: This article is a single step procedure resulting into the closed-hollow obturator as single unit with uniform wall thickness around the hollow space ensuring the least possible weight of the hollow obturator. CONCLUSION: This processing technique achieves predictable internal dimension of the hollow space providing uniform wall thickness of the obturator.

A novel phthalazine based highly selective chromogenic and fluorogenic chemosensor for Co(2+) in semi-aqueous medium: application in cancer cell imaging.

A new phthalazine based chemosensor was developed for the highly selective and sensitive detection of Co(2+) in the mixed solvent system, CH3CN-H2O (1 : 1, v/v). In the presence of Co(2+), the colour of the solution changed from yellow to green; the absorption maxima of was red-shifted from 383 nm to 435 nm, and the fluorescence of at 550 nm was significantly enhanced. The sensor showed a detection limit down to 25 nM by forming a complex species with Co(2+) in 1 : 1 stoichiometry. Furthermore, by means of confocal laser scanning microscopy experiments, it has demonstrated that it can be used as a fluorescent probe for monitoring Co(2+) in living cells.

Maxillomandibular relationship record for implant complete mouth rehabilitation with elastomeric material and facial surface index of existing denture.

INTRODUCTION: The maxillomandibular relationship (MMR) record is a critical step to establish the new occlusion in implant supported complete mouth rehabilitation. Using patients existing denture for recording the MMR requires implant definitive cast to be modified extensively to completely seat the denture (with unaltered flanges) on it. This may influence the correct seating of the denture on the implant definitive cast causing faulty recording of the MMR. MATERIALS AND METHOD: Elastomeric record bases, reinforced with the resin framework, are fabricated and relined with the light body elastomeric material when all the healing abutments are in place. The MMR is recorded with these elastomeric record bases using vacuum formed facial surface index of the occluded existing dentures as a guideline. RESULTS: The elastomeric record bases with facial surface index of the existing dentures can allow clinicians to record MMR records without removing the healing abutments from the mouth with acceptable accuracy. This can save chair-side time of the procedure. The record of facial surfaces of existing complete denture in the form of vacuum formed sheet helps to set the occlusal vertical dimension. CONCLUSION: Use of facial surface index together with the elastomeric record bases can be the useful alternative technique to record the MMR in patients with implant supported full mouth rehabilitation. Further study is required to prove its routine clinical utility.

Highly sensitive ratiometric chemosensor for selective 'naked-eye' nanomolar detection of Co(2+) in semi-aqueous media.

An easy-to-prepare chemosensor, (E)-1-(phthalazine-4-yl)-2-(1-(pyridine-2-yl)ethylidene) hydrazine (3), structurally characterized by single X-ray crystallography, is developed for the selective and sensitive detection of Co(2+) in aqueous media. Chemosensor 3 shows both absorption and fluorescence responses to Co(2+) by forming a 1:1 complex (among the surveyed metal ions) with a detection limit down to 50 nM. It can also be used as a 'naked-eye' sensor due to the outstanding visible and emission color changes from yellow to red and blue to orange, respectively.

Amelogenesis imperfecta with multiple impacted teeth and skeletal class III malocclusion: complete mouth rehabilitation of a young adult.

Amelogenesis imperfecta is an autosomal dominant disorder. It is a group of hereditary diseases showing abnormal enamel density and crown malformation. This clinical report describes the oral rehabilitation of a young adult diagnosed with a variant of hypoplastic amelogenesis imperfecta with multiple impacted teeth and skeletal class III malocclusion. The treatment procedures of teeth extractions, endodontic treatment of remaining teeth followed by post and core restorations, esthetic and functional crown lengthening, and metal ceramic fixed dental prostheses were performed sequentially in the maxillary arch. The mandibular arch was restored with an overdenture. One-year follow-up revealed satisfactory results.

Multidisciplinary treatment approach to restore deep horizontally fractured maxillary central incisor.

This case report demonstrates sequential periodontic, orthodontic and prosthodontic treatment modalities to save and restore deep horizontally fractured maxillary central incisor. The location of fracture was deep in the mucosa which reveals less than 2 mm of tooth structure to receive the crown. The procedures like surgical crown lengthening, endodontic post placement, orthodontic forced eruption, core build-up and metal-ceramic crown restoration were sequentially performed to conserve the fractured tooth. Forced eruption is preferred to surgical removal of supporting alveolar bone, since forced eruption preserves the biologic width, maintains esthetics, and at the same time exposes sound tooth structure for the placement of restorative margins.

Corrigendum to Contractility defects hinder glycoprotein VI-mediated platelet activation and affect platelet functions beyond clot contraction [Research and Practice in Thrombosis and Haemostasis Volume 8, Issue 1, January 2024, 102322].

[This corrects the article DOI: 10.1016/j.rpth.2024.102322.].

Contractility defects hinder glycoprotein VI-mediated platelet activation and affect platelet functions beyond clot contraction.

Background: Active and passive biomechanical properties of platelets contribute substantially to thrombus formation. Actomyosin contractility drives clot contraction required for stabilizing the hemostatic plug. Impaired contractility results in bleeding but is difficult to detect using platelet function tests. Objectives: To determine how diminished myosin activity affects platelet functions, including and beyond clot contraction. Methods: Using the myosin IIA-specific pharmacologic inhibitor blebbistatin, we modulated myosin activity in platelets from healthy donors and systematically characterized platelet responses at various levels of inhibition by interrogating distinct platelet functions at each stage of thrombus formation using a range of complementary assays. Results: Partial myosin IIA inhibition neither affected platelet von Willebrand factor interactions under arterial shear nor platelet spreading and cytoskeletal rearrangements on fibrinogen. However, it impacted stress fiber formation and the nanoarchitecture of cell-matrix adhesions, drastically reducing and limiting traction forces. Higher blebbistatin concentrations impaired platelet adhesion under flow, altered mechanosensing at lamellipodia edges, and eliminated traction forces without affecting platelet spreading, α-granule secretion, or procoagulant platelet formation. Unexpectedly, myosin IIA inhibition reduced calcium influx, dense granule secretion, and platelet aggregation downstream of glycoprotein (GP)VI and limited the redistribution of GPVI on the cell membrane, whereas aggregation induced by adenosine diphosphate or arachidonic acid was unaffected. Conclusion: Our findings highlight the importance of both active contractile and passive crosslinking roles of myosin IIA in the platelet cytoskeleton. They support the hypothesis that highly contractile platelets are needed for hemostasis and further suggest a supportive role for myosin IIA in GPVI signaling.

Electrical impedance measurements can identify red blood cell-rich content in acute ischemic stroke clots ex vivo associated with first-pass successful recanalization.

Background: Electrochemical impedance spectroscopy can determine characteristics such as cell density, size, and shape. The development of an electrical impedance-based medical device to estimate acute ischemic stroke (AIS) clot characteristics could improve stroke patient outcomes by informing clinical decision making. Objectives: To assess how well electrical impedance combined with machine learning identified red blood cell (RBC)-rich composition of AIS clots ex vivo, which is associated with a successfully modified first-pass effect. Methods: A total of 253 clots from 231 patients who underwent thrombectomy in 5 hospitals in France, Japan, Serbia, and Spain between February 2021 and October 2023 were analyzed in the Clotbase International Registry. Electrical impedance measurements were taken following clot retrieval by thrombectomy, followed by Martius Scarlet Blue staining. The clot components were quantified via Orbit Image Analysis, and RBC percentages were correlated with the RBC estimations made by the electrical impedance machine learning model. Results: Quantification by Martius Scarlet Blue staining identified RBCs as the major component in clots (RBCs, 37.6%; white blood cells, 5.7%; fibrin, 25.5%; platelets/other, 30.3%; and collagen, 1%). The impedance-based RBC estimation correlated well with the RBC content determined by histology, with a slope of 0.9 and Spearman's correlation of r = 0.7. Clots removed in 1 pass were significantly richer in RBCs and clots with successful recanalization in 1 pass (modified first-pass effect) were richer in RBCs as assessed using histology and impedance signature. Conclusion: Electrical impedance estimations of RBC content in AIS clots are consistent with histologic findings and may have potential for clinically relevant parameters.