Insights from a proteomic atlas of human Alzheimer's disease brain tissue

There is an urgent need to identify new drug targets for Alzheimer's disease(AD). While new immunotherapies show promise, clinical benefit appears low, and side effects are high. A greater understanding of the disease mechanisms driving AD is an essential factor that will facilitate the identification of new, effective drug targets.

A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper function.In most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell death.The challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological conditions.Such interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical levels.In this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective treatments.These are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

Effect of Electronic Medical Record Utilization on Depression, Anxiety and Stress among Doctors and Nurses in Johor, Malaysia

Background： The usage of modem technology in healthcare record system is now a must throughout the world. However, many doctors and nurses has been reporting facing numerous challenges and obstacles in the implementation. The aim of the present study is to determine the prevalence of depression, anxiety and stress among doctors and nurses who utilize EMR （electronic medical record） and its associated factor. Methods： A comparative cross-sectional study was conducted ~om January till April 2012 among doctors and nurses in two public tertiary hospitals in Johor in which one of them uses EMR and the other one still using the MMR （manual medical record） system. Data was collected using self-administered validated Malay version of DASS-21 （Depression, Anxiety, and Stress Scales-21） items questionnaire. It comprises of socio-demographic and occupational characteristics. Findings： There were 130 respondents with a response rate of 91% for EMR and 123 respondents with a response rate of 86% for MMR. The mean （SD） age of respondents in EMR and MMR groups were 34.7 （9.42） and 29.7 （6.15） respectively. The mean （SD） duration of respondents using EMR was 46.1 （35.83） months. The prevalence of depression, anxiety and stress among respondents using EMR were 6.9%, 25.4% and 12.3%. There were no significant difference between the study groups related to the depression, anxiety and stress scores. In multivariable analysis, the significant factors associated with depression among respondents using EMR was age （OR 1.10, 95% CI 1.02, 1.19）. The significant factors associated with stress among respondents using EMR was marital status （OR 3.33, 95% CI 1.10, 10.09） and borderline significant was computer skill course （OR 2.94, 95% CI 0.98, 8.78）. Conclusion： The prevalence of depression, anxiety and stress of those who uses EMR were within acceptable range. Age, marital status and computer skill are the identified factor associated with the depression and stress level which need to be considered in its implementation.

Prevalence and associated factors of stress, anxiety and depression among emergency medical officers in Malaysian hospitals

BACKGROUND： Demanding profession has been associated with poor psychological health due to multiple factors such as overworking hours and night shifts. This study is to determine prevalence and associated factors of depression, anxiety and stress among medical officers working at emergency department in Malaysian hospitals.METHODS： A cross-sectional study was conducted on 140 emergency department medical officers working at general hospitals from seven Malaysia regions. They were randomly selected and their depression, anxiety and stress level were measured by the 21-item Depression, Anxiety, Stress Scale. RESULTS： The highest prevalence was anxiety （28.6%） followed by depression （10.7%） and stress （7.9%）. Depression, anxiety and stress between seven hospitals were not significantly different （P〉0.05）. Male medical officers significantly experienced more anxiety symptoms than female medical officers （P=0.0022）, however depression and stress symptoms between male and female medical officers were not signi？ cantly different （P〉0.05）. Depression, anxiety and stress were not associated with age, working experience, ethnicity, marital status, number of shifts and type of system adopted in different hospitals （P〉0.05）. CONCLUSION： The prevalence of anxiety was high, whereas for depression and stress were considerably low. Gender was the only factor significantly associated with anxiety. Other factors were not associated with depression, anxiety and stress. Future research should aim to gain better understanding on unique factors that affect female and male medical officers’ anxiety level in emergency setting, thus guide authorities to chart strategic plans to remedy this condition.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

Prevalence of underweight and overweight among school-aged children and it's association with children's sociodemographic and lifestyle in Indonesia

Objectives:Underweight remains a health problem among Indonesian children,and the incidence of overweight continuously increases.This study aims to determine factors associated with underweight and overweight in school-aged children in Indonesia.Methods:This study is a cross-sectional investigation on parents and children aged 6e13 years in elementary schools in Makassar,Indonesia.The participants included 877 children and their parents.Anthropometric data were obtained using standardized equipment,and sociodemographic and lifestyle data were determined using a questionnaire.The nutritional status of the children was assessed based on the child growth standard prescribed by the WHO.Results:The prevalence rates of underweight and overweight among the children were 14.5%and 20.4%,respectively.Underweight was more prevalent in boys.Factors such as mother's level of education,having an underweight father,and playing outdoors on weekends for more than 2 h were significantly associated with underweight children.By contrast,mothers with high levels of education,overweight parents,sleeping for less than 9 h,and playing outdoors on weekends for less than 1 h were significantly associated with overweight children.

Culturally Sensitive Medical Care and Nursing Support: A Study of the Concerns of Foreign Visitors to Japan

Background: Considering the development of international transportation in modern societies, nursing care needs to be sensitive to the cultures and customs of patients from other countries. The purpose of this study is to determine, from the perspective of culturally sensitive nursing support, the cultural practices that foreigners consider important when they visit a Japanese hospital for check-ups or hospitalization. Methods: A survey was completed by 110 foreign participants at a shrine in Kyoto City. The purpose of the survey was to evaluate the concerns of foreign visitors regarding Japanese medical providers, caused by cultural differences such as customs of daily life. The statistical analyses were performed using descriptive statistics as well as cross-tabulation, chi-square, and Fisher’s exact tests. Results: After grouping participants by continent, the top concerns observed in all groups about visiting a Japanese hospital were accessibility to and cost of medical care. First, as for medical facilities, participants from North and South America (North and South American) and Europe (Europeans) were significantly more concerned than those in Asia (Asians) (P P P P P Conclusion: Nurses need opportunities to learn and understand differences in cultures. If nurses have opportunities to learn cultural differences as well as to experience caring for foreign patients, their competencies in culturally sensitive nursing support will improve over time. It can be said that this is an issue not only in Japan but also in all other countries.

Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Comparative Study of the Impact of Climate Variability on Prevalence of Urinary Schistosomiasis： Cases at Sunyani Regional Hospital and among School Children in Atronie, Sunyani

A study has been conducted to determine the impact of climate variability on Schistosoma haematobium infection among patients and school children in Sunyani between 2006 and 2009. Urine samples from the subjects were collected and examined in the laboratory using the Filteration technique for the detection and quantification ofSchistosoma haematobium eggs. The prevalence rate of urinary schistosomiasis at the Sunyani Regional Hospital for 2006, 2007, 2008 and 2009 were found to be 0.24%, 0.55%, 0.55% and 0.75% respectively while that for Methodist Junior High School in 2008 and 2009 were 60.1% and 60.3% respectively. A decrease in the relative humidity and average annual rainfall were identified as factors contributory to the increase in urinary schistosomiasis prevalence rate. The temperature values obtained throughout the study period did not have any significant effect on the prevalence rate. The temperature values, however, were those that enhanced cercarial incubation （15-35 ℃） with a resultant increase in shedding of cercariae leading to more infections among water contacts. The infection rate due to the stream Amama was 20.1%, while that due to river Tano was 36.6%. The highest risk group was children aged 15-19 years. Praziquantel was administered to treat the infection, producing a cure rate of 93%. Recognition of urinary schistosomiasis as a public health problem in Ghana is the main challenge to prevention and control of the disease.

Identification of novel mammalian viruses in tree shrews(Tupaia belangeri chinensis)

The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.

Comments by opponents on the British Medical Association’s guidance on non-therapeutic male circumcision of children seem one-sided and may undermine public health

The British Medical Association(BMA)guidance on non-therapeutic circumcision(NTMC)of male children is limited to ethical,legal and religious issues.Here we evaluate criticisms of the BMA’s guidance by Lempert et al.While their arguments promoting autonomy and consent might be superficially appealing,their claim of high procedural risks and negligible benefits seem one-sided and contrast with high quality evidence of low risk and lifelong benefits.Extensive literature reviews by the American Academy of Pediatrics and the United States Centers for Disease Control and Prevention in developing evidence-based policies,as well as risk-benefit analyses,have found that the medical benefits of infant NTMC greatly exceed the risks,and there is no reduction in sexual function and pleasure.The BMA’s failure to consider the medical benefits of early childhood NTMC may partly explain why this prophylactic intervention is discouraged in the United Kingdom.The consequence is higher prevalence of preventable infections,adverse medical conditions,suffering and net costs to the UK’s National Health Service for treatment of these.Many of the issues and contradictions in the BMA guidance identified by Lempert et al stem from the BMA’s guidance not being sufficiently evidence-based.Indeed,that document called for a review by others of the medical issues surrounding NTMC.While societal factors apply,ultimately,NTMC can only be justified rationally on scientific,evidence-based grounds.Parents are entitled to an accurate presentation of the medical evidence so that they can make an informed decision.Their decision either for or against NTMC should then be respected.

Effect of sphygmomanometer cuff pressure on the differentiation of veins from arteries on ultrasound imaging:an observational cross-sectional study

BACKGROUND:Ultrasound guidance is commonly used for accessing difficult peripheral veins.For successful access,a tourniquet is required for venodilation.Tourniquets decrease the compressibility and increase the diameter of veins;they also obfuscate artery-vein differentiation on ultrasound.We aimed to establish the upper limit of sphygmomanometer cuff pressure that facilitates artery-vein differentiation during ultrasound-guided peripheral intravenous access.METHODS:We employed the sphygmomanometer cuff as a tourniquet for venodilation and tested it on seven participants at six different levels as follows:0 mmHg,DBP/2,DBP,(DBP+SBP)/2,SBP,and SBP+20 mmHg.We used an ultrasound probe attached to a pressure-measuring instrument to record cross-sectional images of the cubital artery and vein.During ultrasonography,compression was applied to the blood vessels through the skin.The following day,we measured the wrist pulse pressure and observed the oximeter pulse wave at six different tourniquet pressure levels.Repeated-measures analysis of variance(ANOVA)on ranks and Tukey’s post-hoc analysis were used for multiple comparisons.RESULTS:Arterial pulsation was maintained at tourniquet pressures between 0 mmHg and(DBP+SBP)/2.However,arterial pulsation decreased or disappeared when the tourniquet pressure reached or exceeded the SBP.Moreover,at this pressure level,the superior compressibility of veins compared to that of arteries was no longer observed.Compression of the artery to 75% and 50% of its original diameter increased arterial pulsation.CONCLUSION:Arterial pulsation and the superior compressibility are useful indicators for differentiating veins from arteries until the tourniquet pressure reaches(DBP+SBP)/2.However,these indicators are not reliable once the tourniquet pressure exceeds the SBP.

Myringoplasty: A comparison of inlay and underlay techniques

Purpose:Myringoplasty aims to improve hearing and prevent otorrhea,making graft uptake rates and hearing crucial considerations.This study analyzed the factors associated with unsuccessful graft uptake and hearing improvement to guide the selection of optimal surgical approaches for myringoplasty.Methods:We retrospectively reviewed 56 ears with chronic otitis media.All patients were followed up for>6 months after tympanic membrane closure surgery.We compared the underlay method using the transcanal approach with the inlay method using the retroauricular approach for myringoplasty in patients with chronic otitis media.The underlay and inlay methods were used for 23 and 33 ears,respectively.The primary outcomes were graft uptake rate and hearing improvement.Additionally,factors such as the location of tympanic membrane perforation,patient age,and the degree of mastoid development were evaluated.Results:The perforation rate was high when the transcanal underlay method was employed to repair perforations in the anterior inferior quadrant.Both the underlay and inlay methods significantly improved hearing.However,the success rate of the inlay method was lower.Within the cases performed using the inlay method,outcomes tended to be poorer in older age groups.There were no significant differences in surgical success rates related to mastoid development.Conclusion:The inlay method using the retroauricular approach is a favorable option for repairing perforations involving the anterior inferior quadrant.However,older patients presented lower rates of hearing improvement when the inlay method was used.

Clinical implications of single cell sequencing for bladder cancer

Bladder cancer(BC)is the 10th most common cancer worldwide,with about 0.5 million reported new cases and about 0.2 million deaths per year.In this scoping review,we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines.We searched PubMed,CENTRAL,Embase,and supplemented with manual searches through the Scopus,and Web of Science for published studies until February 2023.We included original studies that used at least one single-cell technology to study bladder cancer.Forty-one publications were included in the review.Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy.Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples.The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level.Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management.This nascent tool can advance the early diagnosis,prognosis judgment,and targeted therapy of bladder cancer.

Epigenetic memory of drug exposure history controls neural stem cell quiescence in the adult brain

Neural stem cells(NSCs)are the source of all neurons and glial cells(astrocytes and oligodendrocytes)in the central nervous system.The adult mammalian brain retains NSCs in the subgranular zone of the dentate gyrus in the hippocampus and ventricular subventricular zone lining the lateral ventricle(Olpe and Jessberger,2022).Adult NSCs in rodents are preserved throughout life and continuously produce new neurons that integrate into the pre-existing neuronal network.

Neural Wiskott-Aldrich syndrome protein(N-WASP)promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2

Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been established.In this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of PDAC.We found that N-WASP is markedly expressed in clinical patients with PDAC.Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile studies.Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and EMT.We also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were modulated.Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis.These findings may aid in the development of therapeutic strategies against pancreatic cancer.

5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.

Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

Direct visualization of postoperative aortobronchial fistula on computed tomography

BACKGROUND Postoperative aortobronchial fistula(ABF)is a rare complication that can occur in 0.3%-5.0%of patients over an extended period of time after thoracic aortic surgery.Direct visualization of the fistula via imaging is rare.AIM To investigate the relationship between computed tomography(CT)findings and the clinical signs/symptoms of ABF after thoracic aortic surgery.METHODS Six patients(mean age 71 years,including 4 men and 2 women)with suspected ABF on CT(air around the graft)at our hospital were included in this retrospective study between January 2004 and September 2022.Chest CT findings included direct confirmation of ABF,peri-graft fluid,ring enhancement,dirty fat sign,atelectasis,pulmonary hemorrhage,and bronchodilation,and the clinical course were retrospectively reviewed.The proportion of each type of CT finding was calculated.RESULTS ABF detection after surgery was found to have a mean and median of 14 and 13 years,respectively.Initial signs and symptoms were asymptomatic in 4 patients,bloody sputum was found in 1 patient,and fever was present in 1 patient.The complications of ABF included graft infection in 2 patients and graft infection with hemoptysis in 2 patients.Of the 6 patients,3 survived,2 died,and 1 was lost to follow-up.The locations of the ABFs were as follows:1 in the ascending aorta;1 in the aortic arch;2 in the aortic arch leading to the descending aorta;and 2 in the descending aorta.ABFs were directly confirmed by CT in 4/6(67%)patients.Peri-graft dirty fat(4/6,67%)and peri-graft ring enhancement(3/6,50%)were associated with graft infection,endoleaks and pseudoaneurysms were associated with hemoptysis(2/6,33%).CONCLUSION Asymptomatic ABF after thoracic aortic surgery can be confirmed on chest CT.CT is useful for the diagnosis of ABF and its complications.

Hepatic and renal effects of oral stingless bee honey in a streptozotocin-induced diabetic rat model

BACKGROUND Diabetes is known damage the liver and kidney,leading to hepatic dysfunction and kidney failure.Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications.However,the effect of stingless bee honey(SBH)administration in relieving liver and kidney damage in diabetes has not been well-studied.AIM To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced(STZ;55 mg/kg)diabetic Sprague Dawley rats.METHODS The rats were grouped as follows(n=6 per group):non-diabetic(ND),untreated diabetic(UNT),metformin-treated(MET),and SBH+metformin-treated(SBME)groups.After successful diabetic induction,ND and UNT rats were given normal saline,whereas the treatment groups received SBH(2.0 g/kg and/or metformin(250 mg/kg)for 12 d.Serum biochemical parameters and histological changes using hematoxylin and eosin(H&E)and periodic acid–Schiff(PAS)staining were evaluated.RESULTS On H&E and PAS staining,the ND group showed normal architecture and cellularity of Bowman’s capsule and tubules,whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane.The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining,but the two were similar on PAS staining.Likewise,the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining,but it was comparable to the SBH and ND groups on PAS staining.UNT diabetic rats had tubular hydropic tubules,which were smaller than other groups.Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group.Conversely,the UNT group had high glucose levels,which subsequently increased MDA levels,ultimately leading to liver damage.SBH treatment reduced this damage,as evidenced by having the lowest fasting glucose,serum alanine transaminase,aspartate transaminase,and alkaline phosphatase levels compared to other groups,although the levels of liver enzymes were not statistically significant.CONCLUSION The cellularity of the Bowman’s capsule,as well as histological alteration of kidney tubules,glomerular membranes,and liver tissues in diabetic rats after oral SBH resembled those of ND rats.Therefore,SBH exhibited a protective hepatorenal effect in a diabetic rat model.