Reinforced tissue matrix to strengthen the abdominal wall following reversal of temporary ostomies or to treat incisional hernias

BACKGROUND Abdominal wall deficiencies or weakness are a common complication of tem-porary ostomies,and incisional hernias frequently develop after colostomy or ileostomy takedown.The use of synthetic meshes to reinforce the abdominal wall has reduced hernia occurrence.Biologic meshes have also been used to enhance healing,particularly in contaminated conditions.Reinforced tissue matrices(R-TMs),which include a biologic scaffold of native extracellular matrix and a syn-thetic component for added strength/durability,are designed to take advantage of aspects of both synthetic and biologic materials.To date,RTMs have not been reported to reinforce the abdominal wall following stoma reversal.METHODS Twenty-eight patients were selected with a parastomal and/or incisional hernia who had received a temporary ileostomy or colostomy for fecal diversion after rectal cancer treatment or trauma.Following hernia repair and proximal stoma closure,RTM(OviTex®1S permanent or OviTex®LPR)was placed to reinforce the abdominal wall using a laparoscopic,robotic,or open surgical approach.Post-operative follow-up was performed at 1 month and 1 year.Hernia recurrence was determined by physical examination and,when necessary,via computed tomo-graphy scan.Secondary endpoints included length of hospital stay,time to return to work,and hospital readmissions.Evaluated complications of the wound/repair site included presence of surgical site infection,seroma,hematoma,wound dehiscence,or fistula formation.RESULTS The observational study cohort included 16 male and 12 female patients with average age of 58.5 years±16.3 years and average body mass index of 26.2 kg/m^(2)±4.1 kg/m^(2).Patients presented with a parastomal hernia(75.0%),in-cisional hernia(14.3%),or combined parastomal/incisional hernia(10.7%).Using a laparoscopic(53.6%),robotic(35.7%),or open(10.7%)technique,RTMs(OviTex®LPR:82.1%,OviTex®1S:17.9%)were placed using sublay(82.1%)or intraperitoneal onlay(IPOM;17.9%)mesh positioning.At 1-month and 1-year follow-ups,there were no hernia recurrences(0%).Average hospital stays were 2.1 d±1.2 d and return to work occurred at 8.3 post-operative days±3.0 post-operative days.Three patients(10.7%)were readmitted before the 1-month follow up due to mesh infection and/or gastrointestinal issues.Fistula and mesh infection were observed in two patients each(7.1%),leading to partial mesh removal in one patient(3.6%).There were no complications between 1 month and 1 year(0%).CONCLUSION RTMs were used successfully to treat parastomal and incisional hernias at ileostomy reversal,with no hernia recurrences and favorable outcomes after 1-month and 1-year.

Exploring the Impact of Crisis and Trauma on the Mental Health and Psychological Well-Being of University Students in Northern Haiti

In recent decades,Haiti has been subject to man-made and natural disasters that have left its citizens vulnerable to a range of shocks.With a weak state unable to protect its populace,Haitians are exposed to some of the highest levels of poverty and violence in the Western Hemisphere.In recent years,Haitians have experienced two crises that this study analyzes:the instability and political violence of“peyi lòk”as well as the global pandemic of COVID-19.This community-based assessment explores the impact of these two crises on the mental health and psychological well-being of 38 Haitian university students in the understudied northern part of the country.Results indicate that both crises had similarities related to their psychological effects on young people,most notably in terms of traumatic experiences related to threats or violence,forced confinement,and large increases in population-wide uncertainty.Additionally,the extreme violence of“peyi lòk”and the widespread unpredictability of COVID-19 and its effects in the early days of the pandemic resulted in high levels of stress and fear.Both crises also resulted in extreme economic hardship for students,with many reporting difficulties accessing basic needs such as food and water.This study highlights how converging population-level crises in“complex emergencies”can heighten trauma and compromise mental health.

Hemodynamic Profiling Using a Cardiac Index–Systemic Vascular Resistance Plot in Patients with Fontan Circulation

Background: Elevated Fontan pressure (FP) alone cannot fully predict clinical outcomes. We hypothesized thathemodynamic profiling using a cardiac index (CI)-systemic vascular resistance (SVR) plot could characterize clinicalfeatures and predict the prognosis of post-Fontan patients. Methods: We included post-Fontan patients whounderwent cardiac catheterization at age < 10 years. Patients were classified into four categories: A, CI ≥ 3, SVRindex (SVRI) ≥ 20;B, CI < 3, SVRI ≥ 20;C, CI ≥ 3, SVRI < 20;and D, CI < 3, SVRI < 20. The primary outcome wasfreedom from the combined endpoint: new onset of protein-losing enteropathy or plastic bronchitis, heart transplant,and death. Clinical and hemodynamic variables and freedom from the endpoint were compared betweenthe hemodynamic categories and outcome predictors were evaluated. Results: Eighty-three patients wereincluded. Median follow-up was 5.3 years. Category A/B/C/D consisted of 4/15/53/11 patients, respectively. Allthe patients in category A were New York Heart Association I/II and had a significantly lower pulmonary vascularresistance index (PVRI). Patients in category C had lower pulmonary/systemic blood flow. Patients in category Dhad a higher PVRI and had the poorest freedom from the endpoint (44% at 5 years). Elevated FP and category Dwere outcome predictors. Conclusions: CI-SVR plots was a novel adjunctive method for Fontan hemodynamicprofiling.

A cluster-randomized trial comparing two SWITCH implementation support strategies for school wellness intervention effectiveness

Background:The School Wellness Integration Targeting Child Health(SWITCH)intervention has demonstrated feasibility as an implementation approach to help schools facilitate changes in students’physical activity(PA),sedentary screen time(SST),and dietary intake(DI).This study evaluated the comparative effectiveness of enhanced(individualized)implementation and standard(group-based)implementation.Methods:Twenty-two Iowa elementary schools participated,with each receiving standardized training(wellness conference and webinars).Schools were matched within region and randomized to receive either individualized or group implementation support.The PA,SST,and DI outcomes of 1097 students were assessed at pre-and post-intervention periods using the Youth Activity Profile.Linear mixed models evaluated differential change in outcomes by condition,for comparative effectiveness,and by gender.Results:Both implementation conditions led to significant improvements in PA and SST over time(p<0.01),but DI did not improve commensurately(p value range:0.02‒0.05).There were no differential changes between the group and individualized conditions for PA(p=0.51),SST(p=0.19),or DI(p=0.73).There were no differential effects by gender(i.e.,non-significant condition-by-gender interactions)for PA(p_(for interaction)=0.86),SST(p_(for interaction)=0.46),or DI(p_(for interaction)=0.15).Effect sizes for both conditions equated to approximately 6 min more PA per day and approximately 3 min less sedentary time.Conclusion:The observed lack of difference in outcomes suggests that group implementation of SWITCH is equally effective as individualized implementation for building capacity in school wellness programming.Similarly,the lack of interaction by gender suggests that SWITCH can be beneficial for both boys and girls.Additional research is needed to understand the school-level factors that influence implementation(and outcomes)of SWITCH.

Gut microbial regulation of innate and adaptive immunity after traumatic brain injury

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.

Kinetic-Thermodynamic Promotion Engineering toward High-Density Hierarchical and Zn-Doping Activity-Enhancing ZnNiO@CF for High-Capacity Desalination

Despite the promising potential of transition metal oxides(TMOs)as capacitive deionization(CDI)electrodes,the actual capacity of TMOs electrodes for sodium storage is significantly lower than the theoretical capacity,posing a major obstacle.Herein,we prepared the kinetically favorable Zn_(x)Ni_(1−x)O electrode in situ growth on carbon felt(Zn_(x)Ni_(1−x)O@CF)through constraining the rate of OH^(−)generation in the hydrothermal method.Zn_(x)Ni_(1−x)O@CF exhibited a high-density hierarchical nanosheet structure with three-dimensional open pores,benefitting the ion transport/electron transfer.And tuning the moderate amount of redox-inert Zn-doping can enhance surface electroactive sites,actual activity of redox-active Ni species,and lower adsorption energy,promoting the adsorption kinetic and thermodynamic of the Zn_(0.2)Ni_(0.8)O@CF.Benefitting from the kinetic-thermodynamic facilitation mechanism,Zn_(0.2)Ni_(0.8)O@CF achieved ultrahigh desalination capacity(128.9 mgNaCl g^(-1)),ultra-low energy consumption(0.164 kW h kgNaCl^(-1)),high salt removal rate(1.21 mgNaCl g^(-1) min^(-1)),and good cyclability.The thermodynamic facilitation and Na^(+)intercalation mechanism of Zn_(0.2)Ni_(0.8)O@CF are identified by the density functional theory calculations and electrochemical quartz crystal microbalance with dissipation monitoring,respectively.This research provides new insights into controlling electrochemically favorable morphology and demonstrates that Zn-doping,which is redox-inert,is essential for enhancing the electrochemical performance of CDI electrodes.

Multimodality imaging of ovarian cystic lesions: Review with an imaging based algorithmic approach

Ovarian cystic masses include a spectrum of benign, borderline and high grade malignant neoplasms. Imaging plays a crucial role in characterization and pretreatment planning of incidentally detected or suspected adnexal masses, as diagnosis of ovarian malignancy at an early stage is correlated with a better prognosis. Knowledge of differential diagnosis, imaging features, management trends and an algorithmic approach of such lesions is important for optimal clinical management. This article illustrates a multi-modality approach in the diagnosis of a spectrum of ovarian cystic masses and also proposes an algorithmic approach for the diagnosis of these lesions.

Projecting the impact of the coronavirus disease-2019 pandemic on childhood obesity in the United States: A microsimulation model

Purpose:The coronavirus disease-2019(COVID-19)pandemic in the United States led to nationwide stay-at-home orders and school closures.Declines in energy expenditure resulting from canceled physical education classes and reduced physical activity may elevate childhood obesity risk.This study estimated the impact of COVID-19 on childhood obesity.Methods:A microsimulation model simulated the trajectory of a nationally representative kindergarten cohort’s body mass index z-scores and childhood obesity prevalence from April 2020 to March 2021 under the control scenario without COVID-19 and under the 4 alternative scenarios with COVID-19—Scenario 1:2-month nationwide school closure in April and May 2020;Scenario 2:Scenario 1 followed by a 10%reduction in daily physical activity in the summer from June to August;Scenario 3:Scenario 2 followed by 2-month school closure in September and October;and Scenario 4:Scenario 3 followed by an additional 2-month school closure in November and December.Results:Relative to the control scenario without COVID-19,Scenarios 1,2,3,and 4 were associated with an increase in the mean body mass index z-scores by 0.056(95%confidence interval(95%CI):0.0550.056),0.084(95%CI:0.0840.085),0.141(95%CI:0.1400.142),and 0.198(95%CI:0.1970.199),respectively,and an increase in childhood obesity prevalence by 0.640(95%CI:0.5150.765),0.972(95%CI:0.8191.126),1.676(95%CI:1.4751.877),and 2.373(95%CI:2.1352.612)percentage points,respectively.Compared to girls and non-Hispanic whites and Asians,the impact of COVID-19 on childhood obesity was modestly larger among boys and non-Hispanic blacks and Hispanics,respectively.Conclusion:Public health interventions are urgently called to promote an active lifestyle and engagement in physical activity among children to mitigate the adverse impact of COVID-19 on unhealthy weight gains and childhood obesity.

Amine-functionalized low-cost industrial grade multi-walled carbon nanotubes for the capture of carbon dioxide

Industrial grade multi-walled carbon nanotubes(IG-MWCNTs) are a low-cost substitute for commercially purified multi-walled carbon nanotubes(P-MWCNTs). In this work, IG-MWCNTs were functionalized with tetraethylenepentamine(TEPA) for CO2capture. The TEPA impregnated IG-MWCNTs were characterized with various experimental methods including N2adsorption/desorption isotherms, elemental analysis, X-ray diffraction, Fourier transform infrared spectroscopy and thermogravimetric analysis. Both the adsorption isotherms of IGMWCNTs-n and the isosteric heats of different adsorption capacities were obtained from experiments. TEPA impregnated IG-MWCNTs were also shown to have high CO2adsorption capacity comparable to that of TEPA impregnated P-MWCNTs. The adsorption capacity of IG-MWCNTs based adsorbents was in the range of 2.145 to 3.088 mmol/g, depending on adsorption temperatures. Having the advantages of low-cost and high adsorption capacity, TEPA impregnated IG-MWCNTs seem to be a promising adsorbent for CO2capture from flue gas.

Primary sclerosing cholangitis associated colitis: Characterization of clinical, histologic features, and their associations with liver transplantation

BACKGROUND Primary sclerosing cholangitis(PSC)associated inflammatory bowel disease(IBD)is a unique form of IBD(PSC-IBD)with distinct clinical and histologic features from ulcerative colitis(UC)and Crohn disease(CD).In patients with PSC and IBD,the severity of the two disease processes may depend on each other.AIM To study the histologic and clinical features of PSC patients with and without IBD.METHODS We assessed specimens from patients with UC(n=28),CD(n=10),PSC and UC(PSC-UC;n=26);PSC and CD(PSC-CD;n=6);and PSC and no IBD(PSC-no IBD;n=4)between years 1999-2013.PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration.Clinical data including age,gender,age at IBD and PSC diagnoses,IBD duration,treatment,follow-up,orthotopic liver transplantation(OLT)were noted.RESULTS PSC-UC patients had more isolated right-sided disease(P=0.03),and less active inflammation in left colon,rectum(P=0.03 and P=0.0006),and overall(P=0.0005)compared to UC.They required less steroids(P=0.01)and fewer colectomies(P=0.03)than UC patients.The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD.No PSC-CD patients required OLT compared to 38%of PSC-UC(P=0.1).PSC-IBD(PSC-UC and PSCCD)patients with OLT had severe disease in the left colon and rectum(P=0.04).CONCLUSION PSC-UC represents a distinct form of IBD.The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction,however warrants clinical attention and further research.

Current understanding of osteoarthritis pathogenesis and relevant new approaches

Osteoarthritis(OA)is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body.The molecular mechanisms of OA are currently unknown.OA is a heterogeneous disease that affects the entire joint,and multiple tissues are altered during OA development.To better understand the pathological mechanisms of OA,new approaches,methods,and techniques need to be used to understand OA pathogenesis.In this review,we first focus on the epigenetic regulation of OA,with a particular focus on DNA methylation,histone modification,and microRNA regulation,followed by a summary of several key mediators in OA-associated pain.We then introduce several innovative techniques that have been and will continue to be used in the fields of OA and OA-associated pain,such as CRISPR,scRNA sequencing,and lineage tracing.Next,we discuss the timely updates concerning cell death regulation in OA pathology,including pyroptosis,ferroptosis,and autophagy,as well as their individual roles in OA and potential molecular targets in treating OA.Finally,our review highlights new directions on the role of the synovial lymphatic system in OA.An improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA.

Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer

BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are facing issues with toxicity and efficacy against solid tumors,which may be partly due to the lack of patient stratification for effective treatments.To study the need of patient stratification before HDACi treatment,and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.METHODS The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues.The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays,chromatin remodeling and cell death.RESULTS In the present study,the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypoacetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer.The data highlights for the first time that pretreatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation,chromatin relaxation and cell cycle arrest.Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes,including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin,exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.CONCLUSION Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification.Furthermore,HDACi therapy in pretreatment regimes is more effective with chemotherapy drugs,and may aid in predicting individual patient prognosis.

Central line-associated bloodstream infection among children with biliary atresia listed for liver transplantation

BACKGROUND Pre-transplant nutrition is a key driver of outcomes following liver transplantation in children.Patients with biliary atresia(BA) may have difficulty achieving satisfactory weight gain with enteral nutrition alone,and parenteral nutrition(PN) may be indicated.While PN has been shown to improve anthropometric parameters of children with BA listed for liver transplantation,less is known about the risks,particularly infectious,associated with this therapy among this specific group of patients.AIM To describe the incidence,microbiology,and risk factors of central line-associated bloodstream infection(CLABSI) among children with BA listed for liver transplantation.METHODS Retrospective review of children aged ≤ 2-years of age with BA who were listed for primary liver transplantation at Texas Children's Hospital from 2008 through2015(n = 96).Patients with a central line for administration of PN(n = 63) were identified and details of each CLABSI event were abstracted.We compared the group of patients who experienced CLABSI to the group who did not,to determine whether demographic,clinical,or laboratory factors correlated with development of CLABSI.RESULTS Nineteen of 63 patients(30%,95%CI:19,43) experienced 29 episodes of CLABSI during 4800 line days(6.04 CLABSI per 1000 line days).CLABSI was predominantly associated with Gram-negative organisms(14/29 episodes,48%)including Klebsiella spp.,Enterobacter spp.,and Escherichia coli.The sole polymicrobial infection grew Enterobacter cloacae and Klebsiella pneumoniae.Grampositive organisms(all Staphylococcus spp.) and fungus(all Candida spp.)comprised 9/29(31%) and 6/29(21%) episodes,respectively.No demographic,clinical,or laboratory factors were significantly associated with an increased risk for the first CLABSI event in Cox proportional hazards regression analysis CONCLUSION There is substantial risk for CLABSI among children with BA listed for liver transplantation.No clinical,demographic,or laboratory factor we tested emerged as an independent predictor of CLABSI.While our data did not show an impact of CLABSI on the short-term clinical outcome,it would seem prudent to implement CLABSI reduction strategies in this population to the extent that each CLABSI event represents potentially preventable hospitalization,unnecessary healthcare dollar expenditures,and may exact an opportunity cost,in terms of missed allograft offers.

SIMULTANEOUS IMAGING OF A lacZ-MARKED TUMOR AND MICROVASCULATURE MORPHOLOGY IN VIVO BY DUAL-WAVELENGTH PHOTOACOUSTIC MICROSCOPY

Photoacoustic molecular imaging,combined with the reporter-gene technique,can provide a valuable tool for cancer research.The expression of the lacZ reporter gene can be imaged using photoacoustic imaging following the injection of X-gal,a colorimetric assay for the lacZ-encoded enzymeβ-galactosidase.Dual-wavelength photoacoustic microscopy was used to non-invasively image the detailed morphology of a lacZ-marked 9L gliosarcoma and its surrounding microvasculature simultaneously in vivo,with a superior resolution on the order of 10μm.Tumor-feeding vessels were found,and the expression level of lacZ in tumor was estimated.With future development of new absorption-enhancing reporter-gene systems,we anticipate this strategy can lead to a better understanding of the role of tumor metabolism in cancer initiation,progression,and metastasis,and in its response to therapy.

Wnt7b can replace Ihh to induce hypertrophic cartilage vascularization but not osteoblast differentiation during endochondral bone development

Indian hedgehog （Ihh） is an essential signal that regulates endochondral bone development. We have previously shown that Wnt7b promotes osteoblast differentiation during mouse embryogenesis, and that its expression in the perichondrium is dependent on Ihh signaling. To test the hypothesis that Wnt7b may mediate some aspects of Ihh function during endochondral bone development, we activated Wnt7b expression from the R26-Wnt7b allele with Col2-Cre in the Ihh-/- mouse. Artificial expression of Wnt7b rescued vascularization of the hypertrophic cartilage in the Ihh-/- mouse, but failed to restore orthotopic osteoblast differentiation in the perichondrium. Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh-/-; Gli3-/- embryo. Interestingly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area. Thus, Ihh-dependent expression of Wnt7b in the perichondrium may contribute to vascularization of the hypertrophic cartilage during endochondral bone development.

Effect of viscoelasticity on skin pain sensation

Pain sensation may appear under long-lasting mechanical stimulation. Although people have the experience that pain sensation generally decreases with time while the stimulation remains, the underlying mechanism remains elusive. We experimentally studied the thermal and strain rate- dependent viscoelastic behavior of skin in uniaxial stretch and numerically investigated the effects of temperature and strain rate on pain sensation. The results indicate that the viscosity of skin tissue decreases with increasing temperature and reducing strain rate, which subsequently decreases the discharge frequency of skin nociceptor and thus relieves the pain sensation. The results would contribute to the understanding of pain relief mechanism and optimizing for mechanical treatment.

Screen-printed soft triboelectric nanogenerator with porous PDMS and stretchable PEDOT:PSS electrode

The recent development on wearable and stretchable electronics calls for skin conformable power sources that are beyond current battery technologies.Among the many novel energy devices being explored,triboelectric nanogenerator(TENG)made from intrinsically stretchable materials has a great potential to meet the above requirement as being both soft and efficient.In this paper,we present a lithography-free and low-cost TENG device comprising a porous-structured PDMS layer and a stretchable PEDOT:PSS electrode.The porous PDMS structure is formed by using self-assembled polystyrene beads as the sacrificial template and it is highly ordered with great uniformity and high structural stability under compression force.Moreover,the porous PDMS TENG exhibits improved output voltage and current of 1.65 V and 0.54 nA compared to its counterpart with non-porous PDMS with 0.66 V and 0.34 nA.The effect of different loading force and frequency on the output response of the TENG device has also been studied.This work could shed light on diverse structural modification methods for improving the performance of PDMS-based TENG and the development of intrinsically stretchable TENG for wearable device applications.

Nuclear Mechanotransduction under Geometric Constraint

Cells in vivo reside within a complex microenvironment that is rich in biological,chemical and mechanical cues,playing critical roles in regulating cellular activities(e.g.,proliferation,migration,differentiation)both spatially and temporally.Although it is well accepted that biochemical cues can significantly influence cell functions,accumulating evidence has also shown that mechanical feedback from the cell microenvironment(e.g.,stiffness of ECM,morphology,and tension force)also plays an important role in controlling cell fate.Disequilibrium of the mechanical microenvironment is associated with a series of diseases,such as cancer migration and tissue fibrosis.Thus,there is a pressing need to understand how cells transduce these mechanobiological cues.The cell cytoskeleton is linked to both the nuclear lamina via LINC complexes and to focal adhesions.This enables the intriguing possibility that forces directly transduced by the nucleus might in fact affect gene expression.Can force transmitted to nucleus and associated alterations to the special organization of genome inside the nucleus modulate gene expression programmes and change cell behaviors? This kind of putative mechanotransduction dominated by the nucleus is termed as nuclear mechanotransduction.Evidence shows that isolated nuclei regulate their stiffness to in response to force applied on nesprin with integrated nuclear lamina and emerin required.Another example is that the force applied on integrins in focal adhesions can be transmitted through actin filaments to the LINC complex and then stretch the chromatin directly through lamina-chromatin interactions.However,the mechanism of nuclear mechanotransduction is still unclear.Three hypotheses have been proposed.The first proposed mechanism is that the proteins on the nuclear lamina are phosphorylated induced by force and their special organization is changed to regulate downstream signal transduction.Transcription factors like YAP and calcium ions would enter the nucleus in the context of force stretching the nuclear lamina and opening nuclear pore complexes(NPC)and calcium channels.Another proposed hypothesis in this case is that force propagated through the cytoskeleton stretches,opens or condenses chromatin directly,leading to an entirely different genome organization.Nevertheless,due to the lack of research methods and instruments,researchers have not reached a consensus on how cells sense external forces and react specifically through nucleus.In this study,we used micropatterned techniques to modify poly(N-isopropyl-acrylamide)(PA)hydrogel surface with fibronectin(FN)which promote cell adhesion to shape-engineer the cells to investigate the effects of matrix stiffness on nuclear mechanotransduction.To illustrate the impact on nuclear shape induced by matrix stiffness,the nuclei were stained byDAPI and observed by a laser confocal microscopy with small step sizes.The nuclear shape index(NSI),which indicate the variation of projected nuclear shape was firstly researched thoroughly.Meanwhile,the nuclear height,width and volume were characterized in this study.To investigate the force transmitted to the nuclei in cells cultured on hydrogels with multiple stiffness,the cell traction force was measured and the cytoskeleton like actin cap was studied by pharmacological treatments.We also found that the impacts of matrix stiffness on nuclear mechanics,which indicated by the condensation of chromatin and the overexpression of Lamin A/C.

Algorithm to identify circulating tumor cell clusters using in vivo flow cytometer

Recent studies in oncology have addressed the importance of detecting circulating tumor cell clusters because circulating tumor cell clusters might survive and metastasize more easily than single circulating tumor cells.Signals with larger peak widths detected by in vivo flow cytometer(IVFC)have been used to identify cell clusters in previous studies.However,the accuracy of this criterion might be greatly degraded by variance in blood°ow and the rolling behaviors of circulating tumor cells.Here,we propose a criterion and algorithm to distinguish cell clusters from single cells.In this work,we first used area-based and volume-based models for single°uorescent cells.Simulating each model,we analyzed the corresponding morphology of IVFC signals from cell clusters.According to the Rayleigh criterion,the valley between two adjacent peak signals from two distinguishable cells should be lower than 73.5%of the peak values.A novel signal processing algorithm for IVFC was developed based on this criterion.The results showed that cell clusters can be reliably identied using our proposed algorithm.Intravital imaging was also performed to further support our algorithm.With enhanced accuracy,IVFC is a powerful tool to study circulating cell clusters.

INTRODUCTION SPECIAL ISSUE IN HONOR OF STEVEN L.JACQUES FOR HIS 60th BIRTHDAY

Steven L.Jacques received a B.S.degree in Biology from M.I.T.,and an M.S.degree in Electrical Engineering and Computer Science as well as a Ph.D.degree in Biophysics and Medical Physics from the University of California,Berkeley(1984).For his doctoral research,he used dielectric microwave measurements to explore the in vivo distribution of water in the stratum corneum of human skin.