Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

The dual role of striatal interneurons:circuit modulation and trophic support for the basal ganglia

Striatal interneurons play a key role in modulating striatal-dependent behaviors,including motor activity and reward and emotional processing.Interneurons not only provide modulation to the basal ganglia circuitry under homeostasis but are also involved in changes to plasticity and adaptation during disease conditions such as Parkinson's or Huntington's disease.This review aims to summarize recent findings regarding the role of striatal cholinergic and GABAergic interneurons in providing circuit modulation to the basal ganglia in both homeostatic and disease conditions.In addition to direct circuit modulation,striatal interneurons have also been shown to provide trophic support to maintain neuron populations in adulthood.We discuss this interesting and novel role of striatal interneurons,with a focus on the maintenance of adult dopaminergic neurons from interneuronderived sonic-hedgehog.

Making the case for the evolving role of social media in health professions education and a literature review on the application of some in ophthalmology

Background and Objective:Social media(SoMe)has emerged as a tool in health professions education(HPE),particularly amidst the challenges posed by the coronavirus disease 2019(COVID-19)pandemic.Despite the academia’s initial skepticism SoMe has been gaining traction in supporting learning communities,and offering opportunities for innovation in HPE.Our study aims to explore the integration of SoMe in HPE.Four key components were outlined as necessary for a successful integration,and include designing learning experiences,defining educator roles,selecting appropriate platforms,and establishing educational objectives.Methods:This article stemmed from the online Teaching Skills Series module on SoMe in education from the Ophthalmology Foundation,and drew upon evidence supporting learning theories relevant to SoMe integration and models of education.Additionally,we conducted a literature review considering Englishlanguage articles on the application of SoMe in ophthalmology from PubMed over the past decade.Key Content and Findings:Early adopters of SoMe platforms in HPE have leveraged these tools to enhance learning experiences through interaction,dialogue,content sharing,and active learning strategies.By integrating SoMe into educational programs,both online and in-person,educators can overcome time and geographical constraints,fostering more diverse and inclusive learning communities.Careful consideration is,however,necessary to address potential limitations within HPE.Conclusions:This article lays groundwork for expanding SoMe integration in HPE design,emphasizing the supportive scaffold of various learning theories,and the need of furthering robust research on examining its advantages over traditional educational formats.Our literature review underscores an ongoing multifaceted,random application of SoMe platforms in ophthalmology education.We advocate for an effective incorporation of SoMe in HPE education,with the need to comply with good educational practice.

Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

Improving the training abilities of ophthalmic educators: the Ophthalmology Foundation’s initiatives

Our goal as medical educators is for our students to learn what they need to know and competently perform ophthalmic procedures.In addition,the students need to have good communication skills and behave professionally and ethically(1,2).Most medical educators are not taught how to teach but rather learn by role-modeling their mentors.This can be good or bad depending on the mentor!In addition,the amount of knowledge and numbers of surgical procedures is ever increasing and yet,in most countries,the amount of time to train and become competent is not changing.Thus,our goal of creating competent ophthalmologists is ever more challenging.

Prediction of seismic-induced bending moment and lateral displacement in closed and open-ended pipe piles:A genetic programming approach

Ensuring the reliability of pipe pile designs under earthquake loading necessitates an accurate determination of lateral displacement and bending moment,typically achieved through complex numerical modeling to address the intricacies of soil-pile interaction.Despite recent advancements in machine learning techniques,there is a persistent need to establish data-driven models that can predict these parameters without using numerical simulations due to the difficulties in conducting correct numerical simulations and the need for constitutive modelling parameters that are not readily available.This research presents novel lateral displacement and bending moment predictive models for closed and open-ended pipe piles,employing a Genetic Programming(GP)approach.Utilizing a soil dataset extracted from existing literature,comprising 392 data points for both pile types embedded in cohesionless soil and subjected to earthquake loading,the study intentionally limited input parameters to three features to enhance model simplicity:Standard Penetration Test(SPT)corrected blow count(N60),Peak Ground Acceleration(PGA),and pile slenderness ratio(L/D).Model performance was assessed via coefficient of determination(R^(2)),Root Mean Squared Error(RMSE),and Mean Absolute Error(MAE),with R^(2) values ranging from 0.95 to 0.99 for the training set,and from 0.92 to 0.98 for the testing set,which indicate of high accuracy of prediction.Finally,the study concludes with a sensitivity analysis,evaluating the influence of each input parameter across different pile types.

Tilting homeostatic and dyshomeostatic microglial balance in health and disease:transforming growth factor-beta1 as a critical protagonist

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the brain.In the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).

Indirect traumatic optic neuropathy:modeling optic nerve injury in the context of closed head trauma

Traumatic optic neuropathy:Traumatic brain injury is one of the leading causes of disability and mortality in the United States.It impacts people of all ages and demographics,particularly younger males and members of the military.Vision loss is commonly associated with traumatic brain injuries of all severities and can leave patients permanently disabled.This vision loss can be caused by injury to the visual system at multiple levels,including the eyes,optic nerves,and many different sites in the brain and brainstem(Sen,2017).Despite the far-reaching effects of visual impairment after traumatic brain injury,its incidence after traumatic brain injury is not well measured,and few successful treatments have been identified or implemented.

Recent evidence for activity-dependent initiation of sympathetic sprouting and neuropathic pain

Traumatic injury or inflammatory irritation of the peripheral nervous system often leads to persistent pathophysiological pain states.It has been well-documented that,after peripheral nerve injury or inflammation,functional and anatomical alterations sweep over the entire peripheral nervous system including the peripheral nerve endings,the injured or inflamed afferent fibers,the dorsal root ganglion(DRG),and the central afferent terminals in the spinal cord.Among all the changes,ectopic discharge or spontaneous activity of primary sensory neurons is of great clinical interest,as such discharges doubtless contribute to the develop-ment of pathological pain states such as neuropathic pain.Two key sources of abnormal spontaneous activity have been identified following peripheral nerve injury:the injured afferent fibers(neuroma) leading to the DRG,and the DRG somata.The purpose of this review is to provide a global account of the abnormal spontaneous activity in various animal models of pain.Particular attention is focused on the consequence of peripheral nerve injury and localized inflammation.Further,mechanisms involved in the generation of spontaneous activity are also reviewed;evidence of spontaneous activity in contributing to abnormal sympathetic sprouting in the axotomized DRG and to the initiation of neuropathic pain based on new findings from our research group are discussed.An improved understanding of the causes of spontaneous activity and the origins of neuropathic pain should facilitate the development of novel strategies for effective treatment of pathological pain.

Role of Sonic Hedgehog signaling during progression from inflammation to cancer in the stomach

Despite advances in treatment and the declining incidence,gastric cancer remains the second leading cause of cancer-related deaths in the world.Understanding the progression from inflammation to cancer in the stomach is crucial in the development of novel therapies and strategies for treating this disease.Chronic inflammation of the stomach is typically caused by Helicobacter pylori(H.pylori)and resulting lesions may lead to gastric cancer.During the progression from inflammation to cancer,the stomach epithelium changes with evidence of the disruption of normal epithelial cell differentiation and infiltrating inflammatory cells.Coincident with the development of atrophic gastritis and metaplasia,is the loss of the gastric morphogen Sonic Hedgehog(Shh).Given its critical role as a regulator of gastric tissue homeostasis,the disruption of Shh expression during inflammation correlates with the loss of normal epithelial cell differentiation,but this has only recently been rigorously tested in vivo using a unique mouse model of targeted gastric Shh deletion.While pre-neoplastic lesions such as atrophic gastritis and in-testinal metaplasia are associated with the loss of Shh within the acid-secreting glands of the stomach,there is a clear link between elevated Shh and signaling to gastric cancers.The current review focuses on the effects of aberrant Shh expression and its role in the development of gastric cancer,specifically in response to H.pylori infection.

Effect of 5-FU on modulation of disarrangement of immune-associated cytokines in experimental acute pancreatitis

AIM： To investigate the effects of 5-Fluorouracil （5-FU） on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis. METHODS： Male Sprague Dawley rats were assigned to 3 Groups： Group A, sham operated rats as controls （n = 7）; Group B, acute pancreatitis induced by ductal injection with 5% sodium cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the pancreatitis was induced as in Group B, the rats were injected intravenously with 5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after operation （n = 7）, and blood samples were taken for measurement of tumor necrosis factor-α （TNF-α）, interleukin-1 （IL-1）, interleukin-6 （IL-6） （by bioassay）, and interleukin-10 （IL-10）, transforming growth factor-β （TGF-β） （by ELISA）. The wet weight of pancreatic tissue, serum amylase levels and white blood cells were also measured. RESULTS： Four rats in Group B and one in Group C died after pancreatitis was induced. Both pro-inflammatory cytokines （TNF-α, IL-1, IL-6） at the 2 and 6 h period and the anti-inflammatory cytokines （IL-10, TGF-β） at 24 h increased significantly （P 〈 0.05） in rats of Group B. After treatment with 5-FU, TNF-α, IL-1, and IL-6 in serum of rats of Group C were inhibited at 2 and 6 h after operation （P 〈 0.05）, and IL-IO, TGF-13 were inhibited at 24 h compared to Group B （P 〈 0.05）. Obvious improvements in the severity of the acute pancreatitis, including the amylase levels, wet weight of pancreatic tissue and neutrophil counts, were also observed after treatment with 5-FU. CONCLUSION： 5-FU is an anti-metabolic and immunosuppressive agent which can minimize the abnormal immune o/tokine response and relieve the pathophysiological disorders associated with experimental acute pancreatitis.

Geometry Design and Tooth Contact Analysis of Crossed Beveloid Gears for Marine Transmissions

Beveloid gears,also known as conical gears,gain more and more importance in industry practice due to their abilities for power transmission between parallel,intersected and crossed axis.However,this type of gearing with crossed axes has no common plane of action which results in a point contact and low tooth durability.Therefore,a geometry design approach assuming line contact is developed to analyze the tooth engagement process of crossed beveloid gears with small shaft angle for marine transmission applications.The loaded gear tooth contact behavior is simulated by applying a quasi-static analysis to study the effects of gearing parameters on mesh characteristics.Using the proposed method,a series of sensitivity analyses to examine the effects of critical gearing parameters such as shaft angle,cone angle,helix angle and profile-shift coefficient on the theoretical gear mesh is performed.The parametric analysis of pitch cone design shows that the dominant design parameters represented by the angle between the first principle directions（FPD） and normal angular factor are more sensitive to the shaft and cone angles than they are to the helix angle.The theoretical contact path is highly sensitive to the profile-shift coefficient,which is determined from the theoretical tooth contact analysis.The FPD angle is found to change the distribution of contact pattern,contact pressure and root stress as well as the translational transmission error and the variation of the mesh stiffness significantly.The contact pattern is clearly different between the drive and coast sides due to different designed FPD angles.Finally,a practical experimental setup for marine transmission is performed and tooth bearing test is conducted to demonstrate the proposed design procedure.The experimental result compared well with the simulation.Results of this study yield a better understanding of the geometry design and loaded gear mesh characteristics for crossed beveloid gears used in marine transmission.

Ron receptor-dependent gene regulation of Kupffer cells during endotoxemia

BACKGROUND: Ron receptor tyrosine kinase signaling in macrophages, including Kupffer cells and alveolar macrophages,suppresses endotoxin-induced proinflammatory cytokine/chemokine production. Further, we have also identified genes from Ron replete and Ron deplete livers that were differentially expressed during the progression of liver inflammation associated with acute liver failure in mice by microarray analyses.While important genes and signaling pathways have been identified downstream of Ron signaling during progression of inflammation by this approach, the precise role that Ron receptor plays in regulating the transcriptional landscape in macrophages, and particular in isolated Kupffer cells, has still not been investigated.METHODS: Kupffer cells were isolated from wild-type(TK+/+)and Ron tyrosine kinase deficient(TK-/-) mice. Ex vivo, the cells were treated with lipopolysaccharide(LPS) in the presence or absence of the Ron ligand, hepatocyte growth factor-like protein(HGFL). Microarray and qRT-PCR analyses were utilized to identify alterations in gene expression between genotypes.RESULTS: Microarray analyses identified genes expressed differentially in TK+/+ and TK-/- Kupffer cells basally as well as after HGFL and LPS treatment. Interestingly, our studies identified Mefv, a gene that codes for the anti-inflammatory protein pyrin, as an HGFL-stimulated Ron-dependent gene.Moreover, lipocalin 2, a proinflammatory gene, which is induced by LPS, was significantly suppressed by HGFL treatment.Microarray results were validated by qRT-PCR studies on Kupffer cells treated with LPS and HGFL.CONCLUSION: The studies herein suggest a novel mechanism whereby HGFL-induced Ron receptor activation promotes the expression of anti-inflammatory genes while inhibiting genes involved in inflammation with a net effect of diminished inflammation in macrophages.

Mechanical and tribological behaviors of graphene/Inconel 718 composites

Graphene/Inconel 718 composites were innovatively synthesized through selective laser melting,and the mechanical and tribological performances of the grapheme-reinforced Inconel 718 matrix composites were evaluated.The composite microstructures were characterized by XRD,SEM and Raman spectroscopy.The results show that selective laser melting is a viable method to fabricate Inconel 718 matrix composite and the addition of graphene nanoplatelets leads to a significant strengthening of Inconel 718 alloy,as well as the improvement of tribological performance.The yield strength and ultimate tensile strength of 1.0%graphene/Inconel 718 composites(mass fraction)are 42%and 53%higher than those of pure material,and the friction coefficient and wear rate are 22.4%and 66.8%lower than those of pure material.The decrease of fraction coefficient and wear rate is attributed to the improved hardness of composites and the formation of graphene nanoplatelet protective layer on the worn surfaces.

Fabrication and study of supercapacitor electrodes based on oxygen plasma functionalized carbon nanotube fibers

Dry-spun Carbon Nanotube(CNT)fibers were surface-modified by atmospheric pressure oxygen plasma functionalization using a well controlled and continuous process.The fibers were characterized by scanning electron microscopy(SEM),Raman spectroscopy,and X-ray Photoelectron Spectroscopy(XPS).It was found from the conducted electrochemical measurements that the functionalized fibers showed a 132.8% increase in specific capacitance compared to non-functionalized fibers.Dye-adsorption test and the obtained Randles-Sevcik plot demonstrated that the oxygen plasma functionalized fibers exhibited increased surface area.It was further established by Brunauer-Emmett-Teller(BET)measurements that the surface area of the CNT fibers was increased from 168.22 m^2/g to 208.01 m^2/g after plasma functionalization.The pore size distribution of the fibers was also altered by this processing.The improved electrochemical data was attributed to enhanced wettability,increased surface area,and the presence of oxygen functional groups,which promoted the capacitance of the fibers.Fiber supercapacitors were fabricated from the oxygen plasma functionalized CNT fiber electrodes using different electrolyte systems.The devices with functionalized electrodes exhibited excellent cyclic stability(93.2% after 4000 cycles),flexibility,bendability,and good energy densities.At 0.5 m A/cm^2,the EMIMBF4 device revealed a specific capacitance,which is 27% and 65%greater than the specific capacitances of devices using EMIMTFSI and H2SO4 electrolytes,respectively.The practiced in this work plasma surface processing can be employed in other applications where fibers,yarns,ribbons,and sheets need to be chemically modified.

Effects of Honghua preserved amniotic membrane on scar healing in experimental glaucoma surgery

AIM:To investigate the efficacy and safety of Honghua preserved amniotic membrane(AM)for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery.METHODS:Totally 36 rabbits(36 eyes)were randomly divided into 3 groups:the experimental group(ocular trabeculectomy in combination with Honghua preserved AM transplantation),the control group(ocular trabeculectomy surgery in combination with AM implantation),and the blank group(single trabeculectomy).Clinical observations[including intraocular pressure(IOP),filtering blebs and complications],MassonTrichrome staining,real-time quantitative reverse transcription-polymerase chain reaction(real-time PCR),Western blot were performed on different time points(D1,D7,D14,D21 and D56)after the surgery.RESULTS:After operated for 14d,there were statistically significant differences in the filtering blebs compared to the situation before operation(P【0.05),whereas no statistically difference on that among three groups(P】0.05).After 21d,the IOP of experimental group was lowest(P【0.05).There was significant difference between control group and blank group(P【0.05).On postoperative D14,the mean number of fibroblasts in the experimental group was significantlylower(40.6±10.2)compared to those in the control group(54.4±10.8)and blank group(68.2±11.6)(P【0.05,respectively).The mean numbers of the macrophage in the experimental and control groups were respcitively significantly lower versus the blank group(P【0.05,P【0.05,respectively).Compared to that in blank group,the level of transforming growth factor-β(TGF-β1)expression in sclera and conjunctival areas was reduced in the experimental and control groups on protein and mRNA level(P【0.05),but not significant difference between these two groups(P】0.05).CONCLUSION:The trabeculectory surgery with Honghua preserved AM can control IOP,sustain the functional filtration bleb,inhibit the proliferation of fibroblasts and open the filtrating pathway on the rabbit glaucoma models.

The effect of minimal shoes on arch structure and intrinsic foot muscle strength

Background:This prospective study explored the effects of endurance running(ER) in minimal versus standard running shoes on the foot’s superficial layer intrinsic muscles and the function of the longitudinal arch.Our hypothesis was that running in minimal shoes would cause hypertrophy in these muscles and lead to higher,stronger,stiffer arches.Methods:The hypothesis was tested using a sample of 33 healthy runners randomized into two groups,a control group shod in traditional running footwear and an experimental group shod in minimal support footwear,whose feet were scanned in an MRI before and after a 12-week training regime.Running kinematics as well as arch stiffness and height were also assessed before and after the treatment period.Results:Analysis of anatomical cross-sectional areas and muscle volumes indicate that the flexor digitomm brevis muscle became larger in both groups by 11%and 21%,respectively,but only the minimally shod runners had significant areal and volumetric increases of the abductor digiti minimi of 18%and 22%,respectively,and significantly increased longitudinal arch stiffness(60%).Conclusion:These results suggest that endurance running in minimal support footwear with 4 mm offset or less makes greater use of the springlike function of the longitudinal arch,thus leading to greater demands on the intrinsic muscles that support the arch,thereby strengthening the foot.

The Global Stratotype Section and Point （GSSP） for the base of the Katian Stage of the Upper Ordovician Series at Black Knob Ridge, Southeastern Oklahoma, USA

The Global Boundary Stratotype Section and Point （GSSP） for the Katian Stage of the Upper Ordovician Series is defined as the 4.0 m-level above the base of the Bigfork Chert in the Black Knob Ridge section, southeastern Oklahoma. This point in this section is coincident with the first appearance of the graptolite Diplacanthograptus caudatus, which has proved to be a reliable datum for precise worldwide correlation. The FAD ofD. caudatus occurs very near the first occurrences of the graptolites D. lanceolatus, Co.rynoides americanus, Orthograptus pageanus, O. quadrimucronatus, Dicranograptus hians, and Neurograptus margaritatus. This rapid succession of fossil species appearance events provides a secure basis for identification of the base of the Katian Stage of the Upper Ordovician Series and for its global chronostratigraphic correlation.

Effect of Al_(3)Zr particles on hot-compression behavior and processing map for Al-Cu-Li based alloys at elevated temperatures

The influence of Al3Zr particles on the hot compression behavior and processing map(PM)of Al-Cu-Li based alloys under isothermal plane-strain compression in the temperature range of 400-500℃and at the strain rates of 0.01-10 s^-1 was investigated.The corresponding microstructure was analyzed using optical microscopy(OM),electron back-scattered diffraction(EBSD)and transmission electron microscope(TEM).The results showed that dynamic recovery(DRV)played a greater role than dynamic recrystallization(DRX)in dynamic softening.At low temperatures,the Al3Zr particles were the significant barriers to inhibit DRV and DRX grain growth.When the temperature reached 500℃,the Al3Zr particles readily spread along grain boundaries just like a necklace due to the dissolution of Al3Zr particles and rapid diffusion of Zr through grain boundary,resulting in generating the macroscopic cracks and forming an instability domain at 490-500℃,0.01 s^-1 in the PM.