During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increase...During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.展开更多
As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinician...As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinicians or basic scientists define as such.展开更多
Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here...Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here,we introduce pyropheophorbide a-bisaminoquinoline conjugate lipid nanoparticles(PPBC LNPs)as a bimodal system for image-guided phototherapy in bladder cancer treatment.PPBC LNPs not only demonstrate both powerful photodynamic and photothermal effects upon light activation,but also exhibit potent autophagy blockage,effectively inducing bladder cancer cell death.Furthermore,PPBC LNPs possess remarkable photoacoustic(PA)and fluorescence(FL)imaging capabilities,enabling imaging with high-resolution,deep tissue penetration and high sensitivity for tracking drug biodistribution and phototherapy efficacy.Specifically,PA imaging confirms the efficient accumulation of PPBC LNPs within tumor and predicts therapeutic outcomes of photodynamic therapy,while FL imaging confirms their prolonged retention at the tumor site for up to 6 days.PPBC LNPs significantly suppress bladder tumor growth,with several tumors completely ablated following just two doses of the nanoparticles and laser treatment.Additionally,PPBC LNPs were formulated with lipid-based excipients and assembled using microfluidic technology to enhance biocompatibility,stability,and scalability,showing potential for clinical translation.This versatile nanoparticle represents a promising candidate for further development in bladder cancer therapy.展开更多
Autism is a heterogeneous condition with a rising prevalence and demand for specialized care.Autistic children are more likely than neurotypical peers to experience co-occurring conditions(CCs),including medical,psych...Autism is a heterogeneous condition with a rising prevalence and demand for specialized care.Autistic children are more likely than neurotypical peers to experience co-occurring conditions(CCs),including medical,psychiatric,and behavioral issues,highlighting the urgent need for autism-competent healthcare providers in general healthcare.This review aims to equip primary care providers(PCPs)with a concise summary of common CCs and strategies for effective identification.A panel of experts with extensive experience in caring for autistic children collaboratively summarized key literature,research evidence,and existing clinical trial outcomes,supplementing their clinical expertise.Autistic children consistently show higher rates of both medical and mental health issues.Despite greater healthcare utilization,many autistic individuals report unmet needs.CCs can impair behavior,functioning,and well-being,but are often treatable when recognized early.Timely identification and management of medical and psychiatric CCs are critical for improving outcomes for autistic children and their families.This evidence-based review supports PCPs in enhancing their knowledge,fostering early recognition,and delivering comprehensive,responsive care.展开更多
BACKGROUND: Targeted temperature management(TTM) is a common therapeutic intervention, yet its cost-effectiveness remains uncertain. This study aimed to evaluate the real-world cost-effectiveness of TTM compared with ...BACKGROUND: Targeted temperature management(TTM) is a common therapeutic intervention, yet its cost-effectiveness remains uncertain. This study aimed to evaluate the real-world cost-effectiveness of TTM compared with that of conventional care in adult out-of-hospital cardiac arrest(OHCA) survivors using clinical patient-level data.METHODS: We conducted a retrospective cohort study at an academic medical center in the USA to assess the cost-effectiveness of TTM in adult non-traumatic OHCA survivors between 1 January, 2019 and 30 June, 2023. The primary outcome was survival to hospital discharge. Incremental cost-effectiveness ratios(ICERs) were calculated and compared with various decision makers' willingness to pay. Cost-effectiveness acceptability curves were utilized to evaluate the economic attractiveness of TTM. Uncertainty about the incremental cost and effect was explored with a 95% confidence ellipse.RESULTS: Among 925 non-traumatic OHCA survivors, only 30(3%) received TTM. After adjusting for potential confounders, the TTM group did not demonstrate a significantly lower cost(delta cost-$5,141, 95% confidence interval [95% CI]: $-35,347 to $25,065, P=0.79) and higher survival to hospital discharge(delta effect 6%, 95% CI:-11% to 23%, P=0.41). Additionally, a 95% confidence ellipse indicated uncertainty reflected by evidence that the true value of the ICER could be in any of the quadrants of the cost-effectiveness plane.CONCLUSION: Although TTM did not demonstrate a clear survival benefit in this study, its potential cost-effectiveness warrants further investigation with larger sample sizes. These findings highlight the need for additional research to optimize TTM use in OHCA care and inform resource allocation decisions.展开更多
Infiltration and activation of peripheral immune cells are critical in the progression of multiple sclerosis and its experimental animal model,experimental autoimmune encephalomyelitis(EAE).This study investigates the...Infiltration and activation of peripheral immune cells are critical in the progression of multiple sclerosis and its experimental animal model,experimental autoimmune encephalomyelitis(EAE).This study investigates the role of high mobility group box 1(HMGB1)in oligodendrocyte precursor cells(OPCs)in modulating pathogenic T cells infiltrating the central nervous system through the blood-brain barrier(BBB)by using OPC-specific HMGB1 knockout(KO)mice.We found that HMGB1 released from OPCs promotes BBB disruption,subsequently allowing increased immune cell infiltration.The migration of CD4+T cells isolated from EAE-induced mice was enhanced when co-cultured with OPCs compared to oligodendrocytes(OLs).OPC-specific HMGB1 KO mice exhibited lower BBB permeability and reduced immune cell infiltration into the CNS,leading to less damage to the myelin sheath and mitigated EAE progression.CD4+T cell migration was also reduced when co-cultured with HMGB1 knock-out OPCs.Our findings reveal that HMGB1 secretion from OPCs is crucial for regulating immune cell infiltration and provides insights into the immunomodulatory function of OPCs in autoimmune diseases.展开更多
Orthopedic conditions have emerged as global health concerns,impacting approximately 1.7 billion individuals worldwide.However,the limited understanding of the underlying pathological processes at the cellular and mol...Orthopedic conditions have emerged as global health concerns,impacting approximately 1.7 billion individuals worldwide.However,the limited understanding of the underlying pathological processes at the cellular and molecular level has hindered the development of comprehensive treatment options for these disorders.The advent of single-cell RNA sequencing(scRNA-seq)technology has revolutionized biomedical research by enabling detailed examination of cellular and molecular diversity.Nevertheless,investigating mechanisms at the single-cell level in highly mineralized skeletal tissue poses technical challenges.In this comprehensive review,we present a streamlined approach to obtaining high-quality single cells from skeletal tissue and provide an overview of existing scRNA-seq technologies employed in skeletal studies along with practical bioinformatic analysis pipelines.By utilizing these methodologies,crucial insights into the developmental dynamics,maintenance of homeostasis,and pathological processes involved in spine,joint,bone,muscle,and tendon disorders have been uncovered.Specifically focusing on the joint diseases of degenerative disc disease,osteoarthritis,and rheumatoid arthritis using scRNA-seq has provided novel insights and a more nuanced comprehension.These findings have paved the way for discovering novel therapeutic targets that offer potential benefits to patients suffering from diverse skeletal disorders.展开更多
Cardiac arrest poses a significant global public health challenge,manifesting in approximately 550,000 cases annually within the United States.[1]In-hospital cardiac arrest(IHCA)is commonly attributed to airways and r...Cardiac arrest poses a significant global public health challenge,manifesting in approximately 550,000 cases annually within the United States.[1]In-hospital cardiac arrest(IHCA)is commonly attributed to airways and respiratory issues.[2]Recommendations emphasize the expertise of responders in airway management.[3]Various options exist,such as chest compression-only cardiopulmonary resuscitation(CPR),bag-mask ventilation(BMV),and advanced airways.The BMV and advanced airways are not deemed equivalent or superior based on previous evidence.[4]Achieving consistency in choosing and timing the optimal airway approach during IHCA is crucial.The current American Heart Association guidelines suggest an advanced airway strategy when endotracheal intubation(ETI)success rates are high,but the optimal time for advanced airway management remains unclear.[5]Wong et al[6]revealed that survival improved by less than 5 min with advanced airway management.According to a subgroup analysis of IHCA patients in emergency departments(EDs),early intubation was associated with a 1.5-fold greater rate of return of spontaneous circulation(ROSC)than in other locations.[7]ED patients’constant monitoring and immediate management,with readily available intubation equipment,enhance early intubation and survival rates.[6]Nonetheless,IHCA patients intubated within the first 15 min had a lower ROSC rate.展开更多
BACKGROUND Among patients with cirrhosis and pre-malignant or early malignant mucosal lesions,surgical intervention carries a much higher bleeding risk.When such lesions are discovered,endoscopic submucosal dissection...BACKGROUND Among patients with cirrhosis and pre-malignant or early malignant mucosal lesions,surgical intervention carries a much higher bleeding risk.When such lesions are discovered,endoscopic submucosal dissection(ESD)may offer curative therapy with lower risks than surgery and improved outcomes compared to traditional endoscopic resection.AIM To evaluate the outcomes of ESD in patients with cirrhosis.METHODS Patients with cirrhosis undergoing ESD between July 2015 and August 2022 were retrospectively matched in 1:2 fashion to controls based on lesion location,size,and anticoagulation use.Procedural outcomes were compared between groups.RESULTS A total of 64 Lesions from 59 patients were included(16 cirrhosis,43 control).There were no differences in patient or lesion characteristics between groups.En bloc and curative resection was achieved in 84.21%,78.94%of the cirrhosis group and 88.89%,68.89%of controls,respectively,with no significant differences.Cirrhotic patients had significantly higher rates of intra-procedural coagulation grasper use for control of bleeding(47.37%vs 20%;P=0.02).There were otherwise no significant differences in adverse event rates.In the 29 patients with follow up,we found higher rates of recurrence in the cirrhosis group compared to controls(40%vs 5.26%;P=0.019),however this effect did not persist on multivariable analysis controlling for known confounders.CONCLUSION ESD may be safe and effective in patients with cirrhosis.Most procedure related outcomes were not significantly different between groups.Intra-procedural bleeding requiring use of the coagulation grasper use was expectedly higher in the cirrhosis group given the known effects of liver disease on hemostasis.展开更多
Upper gastrointestinal bleeding (UGIB) presents as a prevalent clinical challenge, with annual incidence rates ranging from 80 to 150 cases per 100,000 individuals. Guidelines for managing patients with UGIB due to bl...Upper gastrointestinal bleeding (UGIB) presents as a prevalent clinical challenge, with annual incidence rates ranging from 80 to 150 cases per 100,000 individuals. Guidelines for managing patients with UGIB due to bleeding ulcers recommend a continuous infusion of proton pump inhibitors (PPI). However, studies comparing intermittent dosing of PPI therapy show that this regimen achieves similar clinical benefits. If the clinical efficacy remains equivalent, intermittent dosing will be more cost-effective for patients and the health care system. Our research study aims to analyze the comparative effectiveness of intermittent versus continuous PPI therapy after endoscopic treatment in patients with UGIB, focusing on such endpoints as rebleeding risk at 3-and 7-day mortality rates. Methods: Resources searched included MEDLINE, EMBASE, PUBMED, and the Cochrane Central Register of Controlled Trials databases from January 2010 through December 2023 with the inclusion of meta-analysis, systematic review, review, or ACG guideline recommendations. Results of the analysis show how recommendations regarding high vs. low PPI regimen changed over time: from no difference in regimen in 2010 to recommending continuous regimen in 2012 to declaring insufficient evidence between choosing one regimen over another in 2013 to determine that both regimens were comparable to each other in 2014-2018 and finally to recommending both regimens in 2021. To conclude, our review shows that in patients with bleeding ulcers and high-risk endoscopic findings, intermittent PPI therapy is non-inferior to continuous PPI infusion for three days, seven days bleeding risk or mortality rates;however, it remains challenging to determine the most optimal intermittent regimen due to heterogeneity of RCTs included in meta-analyses, and further trials will need to be performed.展开更多
Achondroplasia is a genetic condition characterized by skeletal dysplasia that results in characteristic craniofacial and spinal abnormalities.It is the most common form of short-limbed skeletal dysplasia.A morbidly o...Achondroplasia is a genetic condition characterized by skeletal dysplasia that results in characteristic craniofacial and spinal abnormalities.It is the most common form of short-limbed skeletal dysplasia.A morbidly obese pregnant patient warrants specific anatomical and physiological considerations,such as a difficult airway with potential hypoxia,full stomach precautions,and a reduced functional residual capacity.Achondroplasia increases the risks of maternal and fetal complications.Although neuraxial techniques are generally preferred for cesarean sections,there is no consensus among patients with achondroplasia.We aimed to discuss the anesthetic challenges in an achondroplastic patient and report our regional anesthesia approach for an elective cesarean section.展开更多
Scoliosis, a three-dimensional deformity of the spine, is commonly encountered in orthopedic and multidisciplinary settings, with idiopathic scoliosis being the most diagnosed form. Complications arising from thoracic...Scoliosis, a three-dimensional deformity of the spine, is commonly encountered in orthopedic and multidisciplinary settings, with idiopathic scoliosis being the most diagnosed form. Complications arising from thoracic chest wall surgeries, including thoracotomy and sternotomy, often include scoliosis among other complications. However, reported prevalence rates of scoliosis following chest wall surgery vary widely. This study aims to compare the prevalence of scoliosis in children who have undergone chest wall surgery to the prevalence of idiopathic scoliosis in the general population, as well as to observe gender ratios and curve direction in post-surgery scoliosis cases. A systematic review was conducted using PubMed and Scopus databases to identify relevant studies. Inclusion criteria comprised studies reporting scoliosis prevalence post chest wall surgery with follow-up times post-surgery. The search yielded 30 articles, all retrospective institutional cohort studies published between 1975 and 2024. Despite heterogeneity in study characteristics, the analysis revealed a 19% prevalence of acquired scoliosis among 5722 children who underwent chest wall surgery, higher than the reported 1% - 4% prevalence in the idiopathic population. Only three studies showed prevalence rates similar to the idiopathic population, possibly due to short follow-up periods. Further research with longer follow-up into skeletal maturity is warranted to better understand the implications of pediatric chest wall surgery on scoliosis development.展开更多
BACKGROUND Primary thumb carpometacarpal(CMC)osteoarthritis is one of the most common conditions encountered by hand surgeons.Of the vast number of operations that have been proposed,none have demonstrated results sig...BACKGROUND Primary thumb carpometacarpal(CMC)osteoarthritis is one of the most common conditions encountered by hand surgeons.Of the vast number of operations that have been proposed,none have demonstrated results significantly superior to trapeziectomy alone.AIM The purpose of our study was to determine why surgeons opt for their technique in treating CMC arthritis.METHODS A cross-sectional survey of active members of the American Society for Surgery of the Hand was conducted to evaluate the reasons behind their preferred technique in the treatment of isolated thumb CMC arthritis.Surgeons were contacted by email once and provided with a link to a de-identified survey consisting of 5 treatment questions and 5 demographic questions.RESULTS Of 950 responses were received.40.5%of surgeons preferred trapeziectomy+ligament reconstruction tendon interposition(LRTI),followed by trapeziectomy+suspensionplasty(28.2%),suture button suspension(5.9%),trapeziectomy alone(4.6%),prosthetic arthroplasty(3.2%),arthrodesis(1.1%),and other(6.6%).Proponents of trapeziectomy+LRTI cited familiarity(73.2%),exposure during fellowship(48.8%)and less proximal migration(60%)to be the main reasons affecting their decision.Surgeons who preferred trapeziectomy+suspensionplasty most reported simplicity(74.9%),fewer complications(45.3%),less proximal migration(43.8%),and avoidance of autogenous tissue harvest(42.7%).Advocates of suture button suspension cited avoidance of autogenous tissue harvest(80.4%),shorter immobilization(76.8%),and quicker recovery(73.2%)with their technique.Advocates of trapeziectomy alone cited simplicity(97.7%),fewer complications(86.4%),and avoidance of autogenous tissue harvest(59.1%).In their comments,45%of surgeons choosing trapeziectomy alone cited evidence as an additional rationale.Advocates of prosthetic arthroplasty cited improved pinch strength(83.3%)and improved range of motion(63.3%),while those preferring arthrodesis cited better pinch strength(90%)and frequently in their comments,durability.Of the surgeons who preferred a technique other than LRTI,41.8%reported they had tried LRTI in the past,citing complexity of the procedure,flexor carpi radialis harvest,and longer operative time as reasons for moving on.CONCLUSION Our study provides an update on current treatment trends and offers new insight into the reasons behind surgeons'decision making in the management of thumb carpometacarpal osteoarthritis.Despite strong Level 1 evidence supporting the use of trapeziectomy alone,our findings demonstrate that most surgeons continue to supplement trapeziectomy with other techniques such as LRTI or suspensionplasty.Several factors including familiarity,personal experience(Level 4 evidence),and comfort may be more influential than Level 1 evidence in determining the techniques in a surgeon's armamentarium.Further prospective studies are needed to determine the optimal technique for surgical management of Eaton stages II-IV CMC arthritis and how these studies will affect surgeons’choice.展开更多
Background and Objective:Advances in teleophthalmology and artificial intelligence(AI)for diabetic retinal screening is of growing public health interest.Currently,only 30–40%of patients with diabetes adhere to recom...Background and Objective:Advances in teleophthalmology and artificial intelligence(AI)for diabetic retinal screening is of growing public health interest.Currently,only 30–40%of patients with diabetes adhere to recommended diabetes screening guidelines.To enhance early detection and reduce vision threatening complications,there has been a growing number of teleophthalmology programs and novel AI algorithms with the aim to improve eye care access.The purpose of this review is to assess current literature on teleophthalmology and AI for use in diabetic retinopathy(DR)screening,and to discuss advances and barriers to these innovative technologies.Methods:Literature review involving teleophthalmology and AI for DR screening,with focus on the past decade.Key Content and Findings:Teleophthalmology has demonstrated the ability to increase DR screening rates,enable earlier eye care access,and reduce healthcare costs.Novel AI-based DR screening programs appear accurate and effective,but detection of other ocular pathologies is still under development and not yet approved in the United States.Logistical,technological,financial,and legal barriers limit widespread adoption and long-term sustainability of teleophthalmology programs.Conclusions:The use of teleophthalmology and AI algorithms expands eye care access and helps prevent vision loss from DR and potentially other sight threatening conditions.Transparency in the process utilized for arriving at a particular diagnosis or decision to refer,often referred to as the“black box”,remains a multifaceted issue within the field of telemedicine for developing trust and improving patient-centered outcomes.展开更多
Sevoflurane induces developmental neurotoxicity in mice;however,the underlying mechanisms remain unclear.Triggering receptor expressed on myeloid cells 2(TREM2)is essential for microglia-mediated synaptic refinement d...Sevoflurane induces developmental neurotoxicity in mice;however,the underlying mechanisms remain unclear.Triggering receptor expressed on myeloid cells 2(TREM2)is essential for microglia-mediated synaptic refinement during the early stages of brain development.We explored the effects of TREM2 on dendritic spine pruning during sevoflurane-induced developmental neurotoxicity in mice.Mice were anaesthetized with sevoflurane on postnatal days 6,8,and 10.Behavioral performance was assessed using the open field test and Morris water maze test.Genetic knockdown of TREM2 and overexpression of TREM2 by stereotaxic injection were used for mechanistic experiments.Western blotting,immunofluorescence,electron microscopy,three-dimensional reconstruction,Golgi staining,and whole-cell patch-clamp recordings were performed.Sevoflurane exposures upregulated the protein expression of TREM2,increased microglia-mediated pruning of dendritic spines,and reduced synaptic multiplicity and excitability of CA1 neurons.TREM2 genetic knockdown significantly decreased dendritic spine pruning,and partially aggravated neuronal morphological abnormalities and cognitive impairments in sevoflurane-treated mice.In contrast,TREM2 overexpression enhanced microglia-mediated pruning of dendritic spines and rescued neuronal morphological abnormalities and cognitive dysfunction.TREM2 exerts a protective role against neurocognitive impairments in mice after neonatal exposures to sevoflurane by enhancing microglia-mediated pruning of dendritic spines in CA1 neurons.This provides a potential therapeutic target in the prevention of sevoflurane-induced developmental neurotoxicity.展开更多
Communicating risks and mitigation benefits associated with natural hazards such as wind to the general public is challenging given the location-dependency of parameters and the complexity of the problem.Web tools pla...Communicating risks and mitigation benefits associated with natural hazards such as wind to the general public is challenging given the location-dependency of parameters and the complexity of the problem.Web tools play a crucial role in educating residents,decision-makers,and stakeholders regarding potential wind hazard losses to,for example,residential buildings.However,a notable gap exists on the practical incorporation of mitigation actions within these tools.This gap hampers the collective awareness and understanding among stakeholders,communities,and citizens regarding the tangible advantages of mitigation strategies in reducing wind-related risks.Furthermore,there exists a need to elucidate the functionality and objectives of these tools in a more accessible manner.This study aims to present and outline the wind risk and mitigation calculator tool(WRMCT)within the Hazardaware platform,which is an address-based risk assessment tool.This tool,developed for 196 counties in the Gulf of Mexico coastal area,facilitates users’education of potential risks and benefits associated with mitigation strategies.WRMCT enables users to access location-specific wind risk and interactively suggests potential mitigation actions along with economic savings to support informed decisions and residential risk reduction.WRMCT intends to enhance users’ability to make informed decisions,take proactive measures in mitigating wind hazards,and contribute to the development of resilient,residential communities.展开更多
Objective and Impact Statement:Human epidermal growth factor receptor 2(HER2)is a critical protein in cancer cell growth that signifies the aggressiveness of breast cancer(BC)and helps predict its prognosis.Here,we in...Objective and Impact Statement:Human epidermal growth factor receptor 2(HER2)is a critical protein in cancer cell growth that signifies the aggressiveness of breast cancer(BC)and helps predict its prognosis.Here,we introduce a deep learning-based approach utilizing pyramid sampling for the automated classification of HER2 status in immunohistochemically(IHC)stained BC tissue images.Introduction:Accurate assessment of IHC-stained tissue slides for HER2 expression levels is essential for both treatment guidance and understanding of cancer mechanisms.Nevertheless,the traditional workflow of manual examination by board-certified pathologists encounters challenges,including inter-and intra-observer inconsistency and extended turnaround times.Methods:Our deep learning-based method analyzes morphological features at various spatial scales,efficiently managing the computational load and facilitating a detailed examination of cellular and larger-scale tissue-level details.Results:This approach addresses the tissue heterogeneity of HER2 expression by providing a comprehensive view,leading to a blind testing classification accuracy of 84.70%,on a dataset of 523 core images from tissue microarrays.Conclusion:This automated system,proving reliable as an adjunct pathology tool,has the potential to enhance diagnostic precision and evaluation speed,and might substantially impact cancer treatment planning.展开更多
基金supported by the National Institute of Environmental Health Sciences(R21ES035492,R21ES035969)National Institutes of Child Health(R01HD090214)(to PA).
文摘During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.
文摘As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinicians or basic scientists define as such.
文摘Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here,we introduce pyropheophorbide a-bisaminoquinoline conjugate lipid nanoparticles(PPBC LNPs)as a bimodal system for image-guided phototherapy in bladder cancer treatment.PPBC LNPs not only demonstrate both powerful photodynamic and photothermal effects upon light activation,but also exhibit potent autophagy blockage,effectively inducing bladder cancer cell death.Furthermore,PPBC LNPs possess remarkable photoacoustic(PA)and fluorescence(FL)imaging capabilities,enabling imaging with high-resolution,deep tissue penetration and high sensitivity for tracking drug biodistribution and phototherapy efficacy.Specifically,PA imaging confirms the efficient accumulation of PPBC LNPs within tumor and predicts therapeutic outcomes of photodynamic therapy,while FL imaging confirms their prolonged retention at the tumor site for up to 6 days.PPBC LNPs significantly suppress bladder tumor growth,with several tumors completely ablated following just two doses of the nanoparticles and laser treatment.Additionally,PPBC LNPs were formulated with lipid-based excipients and assembled using microfluidic technology to enhance biocompatibility,stability,and scalability,showing potential for clinical translation.This versatile nanoparticle represents a promising candidate for further development in bladder cancer therapy.
文摘Autism is a heterogeneous condition with a rising prevalence and demand for specialized care.Autistic children are more likely than neurotypical peers to experience co-occurring conditions(CCs),including medical,psychiatric,and behavioral issues,highlighting the urgent need for autism-competent healthcare providers in general healthcare.This review aims to equip primary care providers(PCPs)with a concise summary of common CCs and strategies for effective identification.A panel of experts with extensive experience in caring for autistic children collaboratively summarized key literature,research evidence,and existing clinical trial outcomes,supplementing their clinical expertise.Autistic children consistently show higher rates of both medical and mental health issues.Despite greater healthcare utilization,many autistic individuals report unmet needs.CCs can impair behavior,functioning,and well-being,but are often treatable when recognized early.Timely identification and management of medical and psychiatric CCs are critical for improving outcomes for autistic children and their families.This evidence-based review supports PCPs in enhancing their knowledge,fostering early recognition,and delivering comprehensive,responsive care.
基金supported by Faculty of MedicineChiang Mai University+2 种基金supported by the National Center for Advancing Translational SciencesNational Institutes of Healththrough grant number UL1 TR001860. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH。
文摘BACKGROUND: Targeted temperature management(TTM) is a common therapeutic intervention, yet its cost-effectiveness remains uncertain. This study aimed to evaluate the real-world cost-effectiveness of TTM compared with that of conventional care in adult out-of-hospital cardiac arrest(OHCA) survivors using clinical patient-level data.METHODS: We conducted a retrospective cohort study at an academic medical center in the USA to assess the cost-effectiveness of TTM in adult non-traumatic OHCA survivors between 1 January, 2019 and 30 June, 2023. The primary outcome was survival to hospital discharge. Incremental cost-effectiveness ratios(ICERs) were calculated and compared with various decision makers' willingness to pay. Cost-effectiveness acceptability curves were utilized to evaluate the economic attractiveness of TTM. Uncertainty about the incremental cost and effect was explored with a 95% confidence ellipse.RESULTS: Among 925 non-traumatic OHCA survivors, only 30(3%) received TTM. After adjusting for potential confounders, the TTM group did not demonstrate a significantly lower cost(delta cost-$5,141, 95% confidence interval [95% CI]: $-35,347 to $25,065, P=0.79) and higher survival to hospital discharge(delta effect 6%, 95% CI:-11% to 23%, P=0.41). Additionally, a 95% confidence ellipse indicated uncertainty reflected by evidence that the true value of the ICER could be in any of the quadrants of the cost-effectiveness plane.CONCLUSION: Although TTM did not demonstrate a clear survival benefit in this study, its potential cost-effectiveness warrants further investigation with larger sample sizes. These findings highlight the need for additional research to optimize TTM use in OHCA care and inform resource allocation decisions.
基金supported by the National Research Foundation of Korea(NRF)funded by the government of the Republic of Korea[2023R1A2C1004955]the Technology Innovation Program funded by the Ministry of Trade,Industry&Energy(Korea)(20009707)+1 种基金the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2020R1A6A3A01099056)the Korea Institute for Advancement of Technology funded by the Ministry of Trade,Industry and Energy(P0025489).
文摘Infiltration and activation of peripheral immune cells are critical in the progression of multiple sclerosis and its experimental animal model,experimental autoimmune encephalomyelitis(EAE).This study investigates the role of high mobility group box 1(HMGB1)in oligodendrocyte precursor cells(OPCs)in modulating pathogenic T cells infiltrating the central nervous system through the blood-brain barrier(BBB)by using OPC-specific HMGB1 knockout(KO)mice.We found that HMGB1 released from OPCs promotes BBB disruption,subsequently allowing increased immune cell infiltration.The migration of CD4+T cells isolated from EAE-induced mice was enhanced when co-cultured with OPCs compared to oligodendrocytes(OLs).OPC-specific HMGB1 KO mice exhibited lower BBB permeability and reduced immune cell infiltration into the CNS,leading to less damage to the myelin sheath and mitigated EAE progression.CD4+T cell migration was also reduced when co-cultured with HMGB1 knock-out OPCs.Our findings reveal that HMGB1 secretion from OPCs is crucial for regulating immune cell infiltration and provides insights into the immunomodulatory function of OPCs in autoimmune diseases.
基金National Key Research and Development Program of China(2022YFA1103202)National Natural Science Foundation of China(82272507,32270887,and 32200654)+6 种基金Natural Science Foundation of Chongqing(CSTB2023NSCQ-ZDJO008)Postdoctoral Innovative Talent Support Program(BX20220397)Independent Research Project of State Key Laboratory of Trauma and Chemical Poisoning(SFLKF202201)Project for Enhancing Innovation of Army Medical University(2023X1839)Talent Innovation Training Program at the Army Medical Center(ZXZYTSYS09)General Hospital of Western Theater Command Research Project(2021-XZYG-B10)University Grants Committee,Research Grants Council of Hong Kong,China(14113723,N_CUHK472/22,C7030-18G,T13-402/17-N,and AoE/M-402/20)。
文摘Orthopedic conditions have emerged as global health concerns,impacting approximately 1.7 billion individuals worldwide.However,the limited understanding of the underlying pathological processes at the cellular and molecular level has hindered the development of comprehensive treatment options for these disorders.The advent of single-cell RNA sequencing(scRNA-seq)technology has revolutionized biomedical research by enabling detailed examination of cellular and molecular diversity.Nevertheless,investigating mechanisms at the single-cell level in highly mineralized skeletal tissue poses technical challenges.In this comprehensive review,we present a streamlined approach to obtaining high-quality single cells from skeletal tissue and provide an overview of existing scRNA-seq technologies employed in skeletal studies along with practical bioinformatic analysis pipelines.By utilizing these methodologies,crucial insights into the developmental dynamics,maintenance of homeostasis,and pathological processes involved in spine,joint,bone,muscle,and tendon disorders have been uncovered.Specifically focusing on the joint diseases of degenerative disc disease,osteoarthritis,and rheumatoid arthritis using scRNA-seq has provided novel insights and a more nuanced comprehension.These findings have paved the way for discovering novel therapeutic targets that offer potential benefits to patients suffering from diverse skeletal disorders.
基金granted by the Faculty of Medicine,Chiang Mai University(Grant No.MC017-65)supported by the National Center for Advancing Translational Sciences,National Institutes of Health,through grant number UL1 TR001860(to WW).
文摘Cardiac arrest poses a significant global public health challenge,manifesting in approximately 550,000 cases annually within the United States.[1]In-hospital cardiac arrest(IHCA)is commonly attributed to airways and respiratory issues.[2]Recommendations emphasize the expertise of responders in airway management.[3]Various options exist,such as chest compression-only cardiopulmonary resuscitation(CPR),bag-mask ventilation(BMV),and advanced airways.The BMV and advanced airways are not deemed equivalent or superior based on previous evidence.[4]Achieving consistency in choosing and timing the optimal airway approach during IHCA is crucial.The current American Heart Association guidelines suggest an advanced airway strategy when endotracheal intubation(ETI)success rates are high,but the optimal time for advanced airway management remains unclear.[5]Wong et al[6]revealed that survival improved by less than 5 min with advanced airway management.According to a subgroup analysis of IHCA patients in emergency departments(EDs),early intubation was associated with a 1.5-fold greater rate of return of spontaneous circulation(ROSC)than in other locations.[7]ED patients’constant monitoring and immediate management,with readily available intubation equipment,enhance early intubation and survival rates.[6]Nonetheless,IHCA patients intubated within the first 15 min had a lower ROSC rate.
基金reviewed and approved by the Baylor College of Medicine Institutional Review Board.
文摘BACKGROUND Among patients with cirrhosis and pre-malignant or early malignant mucosal lesions,surgical intervention carries a much higher bleeding risk.When such lesions are discovered,endoscopic submucosal dissection(ESD)may offer curative therapy with lower risks than surgery and improved outcomes compared to traditional endoscopic resection.AIM To evaluate the outcomes of ESD in patients with cirrhosis.METHODS Patients with cirrhosis undergoing ESD between July 2015 and August 2022 were retrospectively matched in 1:2 fashion to controls based on lesion location,size,and anticoagulation use.Procedural outcomes were compared between groups.RESULTS A total of 64 Lesions from 59 patients were included(16 cirrhosis,43 control).There were no differences in patient or lesion characteristics between groups.En bloc and curative resection was achieved in 84.21%,78.94%of the cirrhosis group and 88.89%,68.89%of controls,respectively,with no significant differences.Cirrhotic patients had significantly higher rates of intra-procedural coagulation grasper use for control of bleeding(47.37%vs 20%;P=0.02).There were otherwise no significant differences in adverse event rates.In the 29 patients with follow up,we found higher rates of recurrence in the cirrhosis group compared to controls(40%vs 5.26%;P=0.019),however this effect did not persist on multivariable analysis controlling for known confounders.CONCLUSION ESD may be safe and effective in patients with cirrhosis.Most procedure related outcomes were not significantly different between groups.Intra-procedural bleeding requiring use of the coagulation grasper use was expectedly higher in the cirrhosis group given the known effects of liver disease on hemostasis.
文摘Upper gastrointestinal bleeding (UGIB) presents as a prevalent clinical challenge, with annual incidence rates ranging from 80 to 150 cases per 100,000 individuals. Guidelines for managing patients with UGIB due to bleeding ulcers recommend a continuous infusion of proton pump inhibitors (PPI). However, studies comparing intermittent dosing of PPI therapy show that this regimen achieves similar clinical benefits. If the clinical efficacy remains equivalent, intermittent dosing will be more cost-effective for patients and the health care system. Our research study aims to analyze the comparative effectiveness of intermittent versus continuous PPI therapy after endoscopic treatment in patients with UGIB, focusing on such endpoints as rebleeding risk at 3-and 7-day mortality rates. Methods: Resources searched included MEDLINE, EMBASE, PUBMED, and the Cochrane Central Register of Controlled Trials databases from January 2010 through December 2023 with the inclusion of meta-analysis, systematic review, review, or ACG guideline recommendations. Results of the analysis show how recommendations regarding high vs. low PPI regimen changed over time: from no difference in regimen in 2010 to recommending continuous regimen in 2012 to declaring insufficient evidence between choosing one regimen over another in 2013 to determine that both regimens were comparable to each other in 2014-2018 and finally to recommending both regimens in 2021. To conclude, our review shows that in patients with bleeding ulcers and high-risk endoscopic findings, intermittent PPI therapy is non-inferior to continuous PPI infusion for three days, seven days bleeding risk or mortality rates;however, it remains challenging to determine the most optimal intermittent regimen due to heterogeneity of RCTs included in meta-analyses, and further trials will need to be performed.
基金supported in part by the University of California Davis Health Department of Anesthesiology and Pain Medicine and an NIH grant(No.UL1 TR000002)from the University of California Davis Health.
文摘Achondroplasia is a genetic condition characterized by skeletal dysplasia that results in characteristic craniofacial and spinal abnormalities.It is the most common form of short-limbed skeletal dysplasia.A morbidly obese pregnant patient warrants specific anatomical and physiological considerations,such as a difficult airway with potential hypoxia,full stomach precautions,and a reduced functional residual capacity.Achondroplasia increases the risks of maternal and fetal complications.Although neuraxial techniques are generally preferred for cesarean sections,there is no consensus among patients with achondroplasia.We aimed to discuss the anesthetic challenges in an achondroplastic patient and report our regional anesthesia approach for an elective cesarean section.
文摘Scoliosis, a three-dimensional deformity of the spine, is commonly encountered in orthopedic and multidisciplinary settings, with idiopathic scoliosis being the most diagnosed form. Complications arising from thoracic chest wall surgeries, including thoracotomy and sternotomy, often include scoliosis among other complications. However, reported prevalence rates of scoliosis following chest wall surgery vary widely. This study aims to compare the prevalence of scoliosis in children who have undergone chest wall surgery to the prevalence of idiopathic scoliosis in the general population, as well as to observe gender ratios and curve direction in post-surgery scoliosis cases. A systematic review was conducted using PubMed and Scopus databases to identify relevant studies. Inclusion criteria comprised studies reporting scoliosis prevalence post chest wall surgery with follow-up times post-surgery. The search yielded 30 articles, all retrospective institutional cohort studies published between 1975 and 2024. Despite heterogeneity in study characteristics, the analysis revealed a 19% prevalence of acquired scoliosis among 5722 children who underwent chest wall surgery, higher than the reported 1% - 4% prevalence in the idiopathic population. Only three studies showed prevalence rates similar to the idiopathic population, possibly due to short follow-up periods. Further research with longer follow-up into skeletal maturity is warranted to better understand the implications of pediatric chest wall surgery on scoliosis development.
文摘BACKGROUND Primary thumb carpometacarpal(CMC)osteoarthritis is one of the most common conditions encountered by hand surgeons.Of the vast number of operations that have been proposed,none have demonstrated results significantly superior to trapeziectomy alone.AIM The purpose of our study was to determine why surgeons opt for their technique in treating CMC arthritis.METHODS A cross-sectional survey of active members of the American Society for Surgery of the Hand was conducted to evaluate the reasons behind their preferred technique in the treatment of isolated thumb CMC arthritis.Surgeons were contacted by email once and provided with a link to a de-identified survey consisting of 5 treatment questions and 5 demographic questions.RESULTS Of 950 responses were received.40.5%of surgeons preferred trapeziectomy+ligament reconstruction tendon interposition(LRTI),followed by trapeziectomy+suspensionplasty(28.2%),suture button suspension(5.9%),trapeziectomy alone(4.6%),prosthetic arthroplasty(3.2%),arthrodesis(1.1%),and other(6.6%).Proponents of trapeziectomy+LRTI cited familiarity(73.2%),exposure during fellowship(48.8%)and less proximal migration(60%)to be the main reasons affecting their decision.Surgeons who preferred trapeziectomy+suspensionplasty most reported simplicity(74.9%),fewer complications(45.3%),less proximal migration(43.8%),and avoidance of autogenous tissue harvest(42.7%).Advocates of suture button suspension cited avoidance of autogenous tissue harvest(80.4%),shorter immobilization(76.8%),and quicker recovery(73.2%)with their technique.Advocates of trapeziectomy alone cited simplicity(97.7%),fewer complications(86.4%),and avoidance of autogenous tissue harvest(59.1%).In their comments,45%of surgeons choosing trapeziectomy alone cited evidence as an additional rationale.Advocates of prosthetic arthroplasty cited improved pinch strength(83.3%)and improved range of motion(63.3%),while those preferring arthrodesis cited better pinch strength(90%)and frequently in their comments,durability.Of the surgeons who preferred a technique other than LRTI,41.8%reported they had tried LRTI in the past,citing complexity of the procedure,flexor carpi radialis harvest,and longer operative time as reasons for moving on.CONCLUSION Our study provides an update on current treatment trends and offers new insight into the reasons behind surgeons'decision making in the management of thumb carpometacarpal osteoarthritis.Despite strong Level 1 evidence supporting the use of trapeziectomy alone,our findings demonstrate that most surgeons continue to supplement trapeziectomy with other techniques such as LRTI or suspensionplasty.Several factors including familiarity,personal experience(Level 4 evidence),and comfort may be more influential than Level 1 evidence in determining the techniques in a surgeon's armamentarium.Further prospective studies are needed to determine the optimal technique for surgical management of Eaton stages II-IV CMC arthritis and how these studies will affect surgeons’choice.
文摘Background and Objective:Advances in teleophthalmology and artificial intelligence(AI)for diabetic retinal screening is of growing public health interest.Currently,only 30–40%of patients with diabetes adhere to recommended diabetes screening guidelines.To enhance early detection and reduce vision threatening complications,there has been a growing number of teleophthalmology programs and novel AI algorithms with the aim to improve eye care access.The purpose of this review is to assess current literature on teleophthalmology and AI for use in diabetic retinopathy(DR)screening,and to discuss advances and barriers to these innovative technologies.Methods:Literature review involving teleophthalmology and AI for DR screening,with focus on the past decade.Key Content and Findings:Teleophthalmology has demonstrated the ability to increase DR screening rates,enable earlier eye care access,and reduce healthcare costs.Novel AI-based DR screening programs appear accurate and effective,but detection of other ocular pathologies is still under development and not yet approved in the United States.Logistical,technological,financial,and legal barriers limit widespread adoption and long-term sustainability of teleophthalmology programs.Conclusions:The use of teleophthalmology and AI algorithms expands eye care access and helps prevent vision loss from DR and potentially other sight threatening conditions.Transparency in the process utilized for arriving at a particular diagnosis or decision to refer,often referred to as the“black box”,remains a multifaceted issue within the field of telemedicine for developing trust and improving patient-centered outcomes.
基金National Natural Science Foundation of China(82072130 and 82001126)Key Medical Research Projects in Jiangsu Province(ZD2022021)+6 种基金Six Talent Peaks Project in Jiangsu Province(WSN-022)Suzhou Clinical Medical Center for Anaesthesiology(Szlcyxzxj202102)Jiangsu Medical Association Anaesthesia Research Project(SYH-32021-0036(2021031))Suzhou Medical Health Science and Technology Innovation Project(SKY2022136)Jiangsu Provincial Colleges of Natural Science General Program(22KJD320002)Health Talent Plan Project in Suzhou(GSWS2022007)Gusu Health Talent Project of Soochow(GSWS2021062).
文摘Sevoflurane induces developmental neurotoxicity in mice;however,the underlying mechanisms remain unclear.Triggering receptor expressed on myeloid cells 2(TREM2)is essential for microglia-mediated synaptic refinement during the early stages of brain development.We explored the effects of TREM2 on dendritic spine pruning during sevoflurane-induced developmental neurotoxicity in mice.Mice were anaesthetized with sevoflurane on postnatal days 6,8,and 10.Behavioral performance was assessed using the open field test and Morris water maze test.Genetic knockdown of TREM2 and overexpression of TREM2 by stereotaxic injection were used for mechanistic experiments.Western blotting,immunofluorescence,electron microscopy,three-dimensional reconstruction,Golgi staining,and whole-cell patch-clamp recordings were performed.Sevoflurane exposures upregulated the protein expression of TREM2,increased microglia-mediated pruning of dendritic spines,and reduced synaptic multiplicity and excitability of CA1 neurons.TREM2 genetic knockdown significantly decreased dendritic spine pruning,and partially aggravated neuronal morphological abnormalities and cognitive impairments in sevoflurane-treated mice.In contrast,TREM2 overexpression enhanced microglia-mediated pruning of dendritic spines and rescued neuronal morphological abnormalities and cognitive dysfunction.TREM2 exerts a protective role against neurocognitive impairments in mice after neonatal exposures to sevoflurane by enhancing microglia-mediated pruning of dendritic spines in CA1 neurons.This provides a potential therapeutic target in the prevention of sevoflurane-induced developmental neurotoxicity.
文摘Communicating risks and mitigation benefits associated with natural hazards such as wind to the general public is challenging given the location-dependency of parameters and the complexity of the problem.Web tools play a crucial role in educating residents,decision-makers,and stakeholders regarding potential wind hazard losses to,for example,residential buildings.However,a notable gap exists on the practical incorporation of mitigation actions within these tools.This gap hampers the collective awareness and understanding among stakeholders,communities,and citizens regarding the tangible advantages of mitigation strategies in reducing wind-related risks.Furthermore,there exists a need to elucidate the functionality and objectives of these tools in a more accessible manner.This study aims to present and outline the wind risk and mitigation calculator tool(WRMCT)within the Hazardaware platform,which is an address-based risk assessment tool.This tool,developed for 196 counties in the Gulf of Mexico coastal area,facilitates users’education of potential risks and benefits associated with mitigation strategies.WRMCT enables users to access location-specific wind risk and interactively suggests potential mitigation actions along with economic savings to support informed decisions and residential risk reduction.WRMCT intends to enhance users’ability to make informed decisions,take proactive measures in mitigating wind hazards,and contribute to the development of resilient,residential communities.
基金supported by the NSF Biophotonics Program(to A.O.)the NIH National Center for Interventional Biophotonic Technologies(P41 to A.O.).
文摘Objective and Impact Statement:Human epidermal growth factor receptor 2(HER2)is a critical protein in cancer cell growth that signifies the aggressiveness of breast cancer(BC)and helps predict its prognosis.Here,we introduce a deep learning-based approach utilizing pyramid sampling for the automated classification of HER2 status in immunohistochemically(IHC)stained BC tissue images.Introduction:Accurate assessment of IHC-stained tissue slides for HER2 expression levels is essential for both treatment guidance and understanding of cancer mechanisms.Nevertheless,the traditional workflow of manual examination by board-certified pathologists encounters challenges,including inter-and intra-observer inconsistency and extended turnaround times.Methods:Our deep learning-based method analyzes morphological features at various spatial scales,efficiently managing the computational load and facilitating a detailed examination of cellular and larger-scale tissue-level details.Results:This approach addresses the tissue heterogeneity of HER2 expression by providing a comprehensive view,leading to a blind testing classification accuracy of 84.70%,on a dataset of 523 core images from tissue microarrays.Conclusion:This automated system,proving reliable as an adjunct pathology tool,has the potential to enhance diagnostic precision and evaluation speed,and might substantially impact cancer treatment planning.
