Hotspots and frontiers of the relationship between gastric cancer and depression:A bibliometric study

BACKGROUND A significant relationship between gastric cancer(GC)and depression has been found in the last 20 years.However,there is no comprehensive information that helps researchers find popular and potential research directions on GC and depression.AIM To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between GC and depression.METHODS We used the Web of Science Core Collection to search and collate the literature on GC and depression from 2000 to 2022 on 31 May,2023.Then,visualization analysis was performed using VOSviewer software(version 1.6.19)and the Bibliometrix package in R software.RESULTS We retrieved 153 pertinent publications from 2000 to 2022.The annual publication count showed an overall upward trend.China had the most prominent publications and significant contributions to this field(n=64,41.83%).Before 2020,most studies focused on“the effect of GC on the development and progression of depression in patients.”The latest research trends indicate that“the effect of depression on the occurrence and development of GC and its mechanism”will receive more attention in the future.CONCLUSION The study of“the effect of depression on the occurrence and development of GC and its mechanism”has emerged as a novel research theme over the past two years,which may become a research hotspot in this field.This study provides new insights into the hotpots and frontiers of the relationship between GC and depression,potentially guiding researchers toward hot research topics in the future.

Single-cell transcriptome profiling of sepsis identifies HLA-DR^(low)S100A^(high)monocytes with immunosuppressive function

Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical outcomes.However,due to the substantial heterogeneity within septic patients,precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.Methods We adopted cross-species,single-cell RNA sequencing(scRNA-seq)analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis.Flow cytometry,laser scanning confocal microscopy(LSCM)imaging and Western blotting were applied to identify the presence of S100A9^(+)monocytes at protein level.To interrogate the immunosuppressive function of this subset,splenic monocytes isolated from septic wild-type or S100a9^(–/–)mice were co-cultured with naive CD4^(+)T cells,followed by proliferative assay.Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.Results scRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis,for which distinct monocyte subsets were enriched in disparate subclusters of septic patients.We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR(HLA-DR),which were prominently enriched in septic patients and might exert immunosuppressive function.By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments,we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice,corresponding to HLA-DR^(low)S100A^(high)monocytes in human sepsis.Moreover,we found that S100A9^(+)monocytes exhibited profound immunosuppressive function on CD4^(+)T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.Conclusions This study identifies HLA-DR^(low)S100A^(high)monocytes correlated with immunosuppressive state upon septic challenge,inhibition of which can markedly mitigate sepsis-induced immune depression,thereby providing a novel therapeutic strategy for the management of sepsis.

Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Updates in the pathophysiological mechanisms of Parkinson's disease: Emerging role of bone marrow mesenchymal stem cells

AIM: To explore the approaches exerted by mesenchymal stem cells(MSCs) to improve Parkinson's disease(PD) pathophysiology.METHODS: MSCs were harvested from bone marrowof femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group(1) was control, Groups(2) and(3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group(2) was left untreated, while Group(3) was treated with single intravenous dose of bone marrow derived MSCs(BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1(TGF-β1), monocyte chemoattractant protein-1(MCP-1) and brain derived neurotrophic factor(BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase(TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1(489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1(89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF(3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA(874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH(1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin(1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin(293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs. CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.

The protection of Thymus vulgaris leaves alcoholic extract against hepatotoxicity of alcohol in rats

Objective:This study was performed to investigate the protective effect of Thymus vulgaris(T.vulgaris) leaves 70%alcoholic extract against alcohol-mediate hepatotoxicity rats.Methods:The protective effect of extract was investigated at dose of 500 mg/kg/day orally against alcohol-mediate hepatotoxicity using adult male Wister albino rats during 21 days.Protective effect of T.vulgaris extract was evaluated comparing with silymarin standard drug al recommended dose(25 mg/kg/day) orally for 21 days.Results:Alcohol-mediate hepatotoxicity rats(alcohol-control) showed hepatocytes distortion represented as marked increment on liver biomarkers;alkaline phosphatase(ALP),aspartate transaminase(AST) and alanine transaminase(ALT) activities,as well as pronounced reduction on total protein and its fractions albumin and globulin corresponding to normal ranges.Addition to oxidative stress status as depletion on glutathione concentration,catalase(CAT),superoxide dismutase(SOD),glutathione reductase(GR),glutathione-S-transferase(GST) and glutathione peroxidase(GPx)activities,concurrence with augmentation oxidative stress parameters;malondyaldchydc(MDA) and hydrogen peroxide(H_2O_2) concentrations comparing to normal values.Alcohol administration elevated total cholesterol(TC),low density lipoprotein cholesterol(LDL-C) and high density lipoprotein cholesterol(HDL-C) comparing to normal ranges.Co-administration T.vulgaris extract with alcohol showed protective effect on hepatocytes manifested as minimizing on ALP.AST and ALT activities and increment on total protein,albumin and globulin production compared to alcohol-control.Antioxidant enzymes activities;CAT.SOD.GR,GST and GPx were significantly magnified,while MDA and H_2O_2 concentration were lessened corresponding to alcohol-control.Also,lipid profile was markedly improved and risk ratio was lowered compared to alcohol-control.These results were confirmed by normalization of degenerated and fibrotic liver tissue as of alcohol-control.Conclusion:T.vulgaris extract appeared hepatoprotective,hypolipidemic and antioxidant activities on alcohol-mediate hepatotoxicity rats compared to silymarin.

Multiple sclerosis: New insights and trends

Multiple sclerosis(MS) is the most famous autoimmune disease attacking the central nervous system. It attacks people from age 20–50 years old and the females' attacks double than males' attacks. MS is an autoimmune disease affecting principally the central nervous system that cause nerve sheath demyelination followed by axon damage and paralysis. MS symptoms include muscle weakness, weak reflexes, muscle spasm, difficult in move, miss-coordination and unbalance with others. There are many factors may be responsible for MS: microbial, viral, smoking, stress, environmental toxins, contaminated diet, and gout. MS is wide spread in the populations in North Europe and this related to lack of vitamin D due to decrease of sunlight exposure. MS biomarkers include nitric oxide, interleukin-6, nitric oxide synthase, fetuin-A and osteopontin. MS is not a genetic disease where MS occurs when human leukocyte antigen system related genes are changed in chromosome 6. The physiology of MS is monitored by activation of immuneinflammatory, oxidative, and nitrosative stress pathways. MS is including two main steps:(1) myelin sheath destruction and formation of lesions and,(2) inflammation. Four types of MS can be distinguished: relapsing-remitting, primary progressive, secondary progressive and progressive relapsing. Nine treatments have been accepted for relapsingremitting MS type: interferon b-1a, interferon b-1b, mitoxantrone, natalizumab, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, and alemtuzumab, however,the only treatment used is mitoxantrone for progressive MS but many of MS treatments side effects are recorded. Complementary treatments also used in MS treatments such as:vitamin D, Yoga, medicinal plants, oxygen therapy, acupuncture and reflexology.

Protective effect of natural products and hormones in colon cancer using metabolome:A physiological overview

Globally, the third cause of males cancer and the fourth cause of females cancer is colon cancer(CC). In Egypt, high CC percentage occurs in children and in individuals below 40 years of age. The complete loss of biological enzyme function is the main cause of CC and consequently CC increased in smoking and pollution exposure. The aim of this review is to focus on the application of metabolome as a physiological tool that can play an important role in preventing CC incidence by natural products and hormones. The dietary factors, intestinal micro-flora and endogenously produced metabolites are the main three causes that produce free radicals in the colon. A correlation occurs between the enzyme activity and CC polymorphisms or property. Nowadays metabolome is applied with the progress of different analytical methods, data bases and tools for cancer predication and stimulation especially in CC cases. Metabolism is defined as intracellular chemical reactions that produce chemical substances and energies sustaining life. Metabolic pathway networks are also composed of links that are defined as transformation of chemical structures between two metabolites and an enzyme reaction. The most important advantage of metabolome is its ability to analyze metabolites from any source, regardless of origin, where the application of liquid chromatography combined with mass spectra in metabolome analysis to a series of cancer cell lines that were progressively more tumorigenic due to the induction of 1,2,3 or 4 oncogenes to cell lines could be a metabolome example application. In conclusion, natural products and hormones are very important in preventing CC in humans and animal models where both natural products and hormones play a significant and important effect in regulating physiological process especially in CC cases. In this situation, metabolome must increase in its application in the future for the diagnosis of CC cases.

New trends in pharmacological treatment of acute kidney injury

Acute kidney injury,previously known as acute renal failure(AKI),is defined as an abrupt decrease in kidney function that occurs within hours or days.This new nomenclature opens a new door for possibility of treatment of developing renal injury before progression to unresolved renal failure.AKI arises due to diverse etiologic factors that rely mainly on three categories namely,prerenal,intrinsic renal,and post-renal factors with different clinical pictures,and confers a spectrum of injury ranging from mild to severe and sometimes leads to end-stage renal disease.Complexity of pathogenesis and other factors generate barriers to developing effective treatments despite a large number of experimental and clinical studies.In this review,recent advances in the potential of the currently used drugs for renoprotection,novel pharmacological targets,and prospective therapeutics for AKI are discussed.The information in this review was extracted from electronic resources(Pub Med,Google Scholar,Wiley,Science Direct,Springer),and English scientific books by using keywords including kidney,injury,recent therapy,and pharmacological targets.The articles were carefully checked for their relevance to the current manuscript.Recent targets of cellular repair or regenerative processes involved in AKI such as autophagy,ferroptosis inhibition,and p53 antagonism seem to be effective in disease control.This may help researchers and clinicians to understand how to target the interrelated molecular and cellular mechanisms underlying the pathogenesis of AKI.

Mortality and morbidity due to the failure to treat mild anemia unrelated to cancer in elderly Americans—Review of the literature and case presentation

Even mild iron deficiency anemia, as defined by the World Health Organization, is associated with increased mortality and significant morbidity in elderly individuals who are cancer free. Yet, anemia in the elderly is often dismissed as a benign sign of aging. This problem is exacerbated by the fact that elderly individuals often suffer from gastrointestinal complaints that preclude treatment with iron supplements by mouth. The FDA has approved two brands of injectable iron for treating such patients. Nonetheless, a major American health maintenance organization refuses to treat elderly patients with injectable iron, even when it is indicated, unless their anemia is associated with cancer. This may well reflect a public health crisis afflicting many elderly residents of the United States.

An online diabetic retinopathy screening tool for patients with type 2 diabetes

AIM:To develop a useful diabetic retinopathy(DR)screening tool for patients with type 2 diabetes mellitus(T2DM).METHODS:A DR prediction model based on the Logistic regression algorithm was established on the development dataset containing 778 samples(randomly assigned to the training dataset and the internal validation dataset at a ratio of 7:3).The generalization capability of the model was assessed using an external validation dataset containing 128 samples.The DR risk calculator was developed through We Chat Developer Tools using Java Script,which was embedded in the We Chat Mini Program.RESULTS:The model revealed risk factors(duration of diabetes,diabetic nephropathy,and creatinine level)and protective factors(annual DR screening and hyperlipidemia)for DR.In the internal and external validation,the recall ratios of the model were 0.92 and 0.89,respectively,and the area under the curve values were 0.82 and 0.70,respectively.CONCLUSION:The DR screening tool integrates education,risk prediction,and medical advice function,which could help clinicians in conducting DR risk assessments and providing recommendations for ophthalmic referral to increase the DR screening rate among patients with T2DM.

Artificial intelligence in small intestinal diseases:Application and prospects

The small intestine is located in the middle of the gastrointestinal tract,so small intestinal diseases are more difficult to diagnose than other gastrointestinal diseases.However,with the extensive application of artificial intelligence in the field of small intestinal diseases,with its efficient learning capacities and computational power,artificial intelligence plays an important role in the auxiliary diagnosis and prognosis prediction based on the capsule endoscopy and other examination methods,which improves the accuracy of diagnosis and prediction and reduces the workload of doctors.In this review,a comprehensive retrieval was performed on articles published up to October 2020 from PubMed and other databases.Thereby the application status of artificial intelligence in small intestinal diseases was systematically introduced,and the challenges and prospects in this field were also analyzed.

Efficient and rapid conversion of human astrocytes and ALS mouse model spinal cord astrocytes into motor neuron-like cells by defined small molecules

Background: Motor neuron degeneration or loss in the spinal cord is the characteristic phenotype of motor neuron diseases or spinal cord injuries. Being proliferative and located near neurons, astrocytes are considered ideal cell sources for regenerating neurons.Methods: We selected and tested different combinations of the small molecules for inducing the conversion of human and mouse astrocytes into neurons. Microscopic imaging and immunocytochemistry analyses were used to characterize the morphology and phenotype of the induced neurons while RT-q PCR was utilized to analyze changes in gene expression. In addition, whole-cell patch-clamp recordings were measured to examine the electrophysiological properties of induced neurons.Results: The results showed that human astrocytes could be rapidly and efficiently converted into motor neuronlike cells by treatment with defined small molecules, with a yield of over 85% motor neuron-like cells attained. The induced motor neuron-like cells expressed the pan-neuronal markers TUJ1, MAP2, Neu N, and Synapsin 1 and motor neuron markers HB9, ISL1, CHAT, and VACh T. During the conversion process, the cells did not pass through a proliferative neural progenitor cell intermediate. The induced motor neurons were functional, showing the electrophysiological properties of neurons. The same chemical cocktail could induce spinal cord astrocytes from an amyotrophic lateral sclerosis mouse model carrying a SOD1 mutation to become motor neuron-like cells that exhibited a decrease in cell survival and an increase in oxidative stress compared to that observed in wild-type MNs derived from healthy mice. Moreover, the chemical induction reduced oxidative stress in the mutant astrocytes.Conclusions: The results of the present study demonstrated the feasibility of chemically converting human and mouse astrocytes into motor neuron-like cells that are useful for neurodegenerative disease modeling and regenerative medicine.

Approach to pharmacological and clinical applications of Anisi aetheroleum

Anisi aetheroleum is the oil obtained from Pimpinella anisuin L.(P.anisuin) by steam distillation.P.anisuin seeds were air-dried,and then the dry seeds were crushed,pulverized,and weighed in sequence for anise oil preparation.P.anisuin is one of the oldest medicinal plants that belong to family Apiaceae.The fruit of P.anisuin is harvested in August and September.P.anisuin is widespread in Asia,Africa and Europe.Local names of P.anisuin include anise,anisoon,roomy,saunf,sweet cumin and yansoon.The anise oil odour is aromatic while the oil tastes sweet.The average daily dose of Anisi aetheroleum is 0.3 g.transAnethole is the major ingredient of the anise oil.Anisi aetheroleum also displays a protective action against neurotoxicity.In addition.Anisi aetheroleum increases glucose absorption and reduces urine output in the rat.The plant oil have pharmacological(antimicrobial,hepatoprotective.anticonvulsant,anti-inflammatory,antispasmodic,bronchodilator.estrogenic,expectorant and insecticidal) effects and clinical effects on nausea,constipation,menopausal period,virus,diabetes,obesity and sedative action.Owing to the wide application of Anisi aetheroleum in pharmacological and clinical fields,it is recommended for more clinical trails to discover a new medication from the active constituents of the plant oil in the future to treat human diseases especially chronic ones.

Protective effect of ashwagandha (Withania somnifera) against neurotoxicity induced by aluminum chloride in rats

Objective: To evaluate the neuroprotective effect of ashwagandha extract against aluminum chloride-induced neurotoxicity in rats. Methods: Rats were divided into control, aluminumintoxicated rats treated daily with aluminum trichloride(Al Cl3)(100 mg/kg, orally) for 30 d and aluminum-intoxicated animals protected by receiving daily ashwagandha extract(200 mg/kg, orally) one hour before Al Cl3 administration for 30 d. Levels of lipid peroxidation, nitric oxide, reduced glutathione and tumor necrosis factor-α were measured in the cortex, hippocampus and striatum. In addition, the activities of Na+, K+, ATPase and acetylcholinesterase were determined in the three studied brain regions. Results: Aluminum increased the levels of lipid peroxidation and nitric oxide in the cortex, hippocampus and striatum and decreased the reduced glutathione level in the hippocampus and striatum. In rats protected with ashwagandha extract, non significant changes were observed in lipid peroxidation, nitric oxide and reduced glutathione. In addition, ashwagandha extracts prevented the increased activity of acetylcholinesterase and Na+, K+, ATPase induced by Al Cl3 in the cortex, hippocampus and striatum. The present findings also showed that the significant increase in tumor necrosis factor-α induced by Al Cl3 in the cortex and hippocampus was prevented by ashwagandha extract. Conclusions: The present results suggest that ashwagandha extract possesses antioxidant and anti-inflammatory effects against aluminum neurotoxicity. In addition, ashwagandha extract could prevent the decline in cholinergic activity by maintaining normal acetylcholinesterase activity. The later effect could recommend the use of ashwagandha as a memory enhancer.

Proteomic approach in human health and disease: Preventive and cure studies

Proteomic is a branch of science that deals with various numbers of proteins where proteins are essential human constituents.Proteomic has a lot of functions inside the human and animal living organisms.This review helps to make a thought on the importance of proteomic application in human health and disease with special reference to preventive and cure studies.The human health can be divided into physical and mental health.The physical health relates to keeping human body state in a good health and to nutritional type and environmental factors.The mental health correlates to human psychological state.The main factors that affect the status of human health are human diet,exercise and sleep.The healthy diet is very important and needs to maintain the human health.The training program exercise improves human fitness and overall health and wellness.The sleep is a vital factor to sustain the human health.The human disease indicates abnormal human condition which influences the specific human part or the whole human body.There are external and internal factors which induce human disease.The external factors include pathogens while internal factors include allergies and autoimmunity.There are 4 principle types of human diseases:(1)infectious disease,(2)deficiency disease,(3)genetic disease and(4)physiological disease.There are many and various external microbes'factors that induce human infectious disease and these agents include viruses,bacteria,fungi and protozoa.The lack of necessary and vital dietary rudiments such as vitamins and minerals is the main cause of human deficiency disease.The genetic disease is initiated by hereditary disturbances that occur in the human genetic map.The physiological disease occurs when the normal human function body is affected due to human organs become malfunction.In conclusion,proteomic plays a vital and significant role in human health and disease.

A lipidomic concept in infectious diseases

Infectious diseases resemble a great threat to the human health according to World Health Organization where about 17% of all deaths(z9.2 million deaths) in 2013 recorded are related to infectious diseases. The pathogenic microorganisms such as bacteria, viruses,fungi and parasites are the principle causes of infectious diseases. Ebola, AIDS, dengue,hepatitis, malaria, tuberculosis and schistosomiasis are among 216 infectious diseases found where the immunity represents the first line defense in infection. Lipidomic includes examination of different biological lipids in the biological cell. The lipidomic research covers all aspects of individual lipid molecule including its structure, function,connection with other cell constituents such as protein, lipid, and metabolite in both health and disease conditions. Details of cell biology obtained from different pathogens(viruses, bacteria, and parasites) provide a great data on molecular structure of hostpathogen relation and consequently on infection process. The lipids here play a very important role in many processes involved in host-pathogen relations. The role of lipid in host-pathogen link includes many processes in(1) structural host constituents,(2) host recognition,(3) intracellular transferring, and(4) energy and resource homeostasis during pathogen duplication. There are many lipid phosphatases, kinases, and lipases molecules that greatly involved in these processes and controlling pathogen expression and infection progress. The cell lipid metabolism depends on an adequate energy stores that push the infection to be accelerated and disease symptoms to be appeared. Consequently, future lipidomics studies are the basic for detecting the lipid role in host-pathogen relations which help in therapy advances and biomarkers development.

Lipidome is lipids regulator in gastrointestinal tract and it is a life collar in COVID-19:A review

The term lipidome is mentioned to the total amount of the lipids inside the biological cells.The lipid enters the human gastrointestinal tract through external source and internal source.The absorption pathway of lipids in the gastrointestinal tract has many ways;the 1st way,the lipid molecules are digested in the lumen before go through the enterocytes,digested products are re-esterified into complex lipid molecules.The 2nd way,the intracellular lipids are accumulated into lipoproteins(chylomicrons)which transport lipids throughout the whole body.The lipids are re-synthesis again inside the human body where the gastrointestinal lipids are:(1)Transferred into the endoplasmic reticulum;(2)Collected as lipoproteins such as chylomicrons;or(3)Stored as lipid droplets in the cytosol.The lipids play an important role in many stages of the viral replication cycle.The specific lipid change occurs during viral infection in advanced viral replication cycle.There are 47 lipids within 11 lipid classes were significantly disturbed after viral infection.The virus connects with blood-borne lipoproteins and apolipoprotein E to change viral infectivity.The viral interest is cholesterol-and lipid raft-dependent molecules.In conclusion,lipidome is important in gastrointestinal fat absorption and coronavirus disease 2019(COVID-19)infection so lipidome is basic in gut metabolism and in COVID-19 infection success.

State of the Art in Cardiac Intervention: A Case Report

The first acute myocardial infarction (MI) of an elderly male was determined through angiography to be due to an infarct of the circumflex artery. The angiogram also revealed chronic occlusion and diffuse disease of the left anterior descending artery (LAD). This had been compensated for by collateral circulation from the right coronary artery. Since the patient had no prior history of coronary artery disease, the chronic and collateralized disease of the LAD was presumed to be stable and this artery was not treated. Due to a history of aspirin intolerance a bare metal stent was implanted in the circumflex artery. Within hours after stenting the patient had a second acute MI. Despite no change in the angiogram, the EKG suggested that the LAD was the source of the second MI. Indeed, a drug-eluting stent implanted in the LAD resolved the patient’s signs and symptoms and he was discharged with a favorable outcome. The surprising second MI and the inconsistent stenting illustrate that when the unexpected occurs, there is no substitute for the judgment of a skilled clinician.

Implications of rare neurological disorders and perceptual errors in natural and synthetic consciousness

Recent theories on natural and synthetic consciousness overlook the geometric structure necessary for awareness of 3-dimensional space, as strikingly illustrated by left-neglect disorder. Furthermore, awareness of 3-dimensional space entails some surprisingly tenacious optical illusions, as demonstrated by an experiment in the text. Awareness of linear time is also crucial and complex. As a consequence, synthetic consciousness cannot be realized by simply intercomnecting a large number of electronic circuits constructed from ordinary chips and transistors. Since consciousness is a subjective experience, there is no sufficient condition for consciousness that can be experimentally confirmed. The most we can hope for is agreement on the necessary conditions for consciousness. Toward that end, this paper reviews some relevant clinical phenomena.

Effect of Tirapazamine and Mild Temperature Hyperthermia on the Recovery from Radiation-Induced Damage in Pimonidazole-Unlabeled Quiescent Tumor Cell Population

The aim in this study is to examine the effect of tirapazamine (TPZ) and mild temperature hyperthermia (MTH) on the repair of radiation-induced damage in pimonidazole-unlabeled quiescent (Q) tumor cells. Labeling of proliferating (P) cells in C57BL/6J mice bearing EL4 tumors was achieved by continuous administration of 5-bromo-2-deoxyuridine (BrdU). Tumors were irradiated with γ-rays at 1 h after the administration of pimonidazole followed by TPZ treatment or MTH. Twenty-four hours later, assessment of the responses of Q and total (= P + Q) cells were based on the frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of the pimonidazole-unlabeled tumor cell fractions was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. With γ-rays only, the pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q cells than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using a delayed assay, was more clearly observed in Q cells than total cells. Post-irradiation MTH more remarkably repressed the decrease in radio-sensitivity in the Q cell than the total cells. Post-irradiation TPZ administration produced a large radio-sensitizing effect on both total and Q cells, especially on Q cells. On the other hand, in pimonidazole-unlabeled cell fractions in both total and Q cells, TPZ suppressed the reduction in sensitivity due to delayed assay much more efficiently than MTH, whereas no radio-sensitizing effect was produced. Not only through suppressing the recovery from radiation-induced damage but also through radio-sensitizing effect, post-irradiation TPZ administration is very useful for repressing the increase in the difference in radio-sensitivity due to the delayed assay not only between total and Q tumor cells but also between the pimonidazole-unlabeled and the whole cell fractions within the total and Q tumor cells.