Diabetes mellitus,a chronic disease of metabolism,is characterized by a disordered production or cellular utilization of insulin.Diabetic foot disease,which comprises the spectrum of infection,ulceration,and gangrene,...Diabetes mellitus,a chronic disease of metabolism,is characterized by a disordered production or cellular utilization of insulin.Diabetic foot disease,which comprises the spectrum of infection,ulceration,and gangrene,is one of the most severe complications of diabetes and is the most common cause of hospitalization in diabetic patients.The aim of this study is to provide an evidence-based overview of diabetic foot complications.Due to neuropathy,diabetic foot infections can occur in the form of ulcers and minor skin lesions.In patients with diabetic foot ulcers,ischemia and infection are the main causes of non-healing ulcers and amputations.Hyperglycemia compromises the immune system of individuals with diabetes,leading to persistent inflammation and delayed wound healing.In addition,the treatment of diabetic foot infections is challenging due to difficulty in accurate identification of pathogenic microorganisms and the widespread issue of antimicrobial resistance.As a further complicating factor,the warning signs and symptoms of diabetic foot problems can easily be overlooked.Issues associated with diabetic foot complications include peripheral arterial disease and osteomyelitis;accordingly,the risk of these complications in people with diabetes should be assessed annually.Although antimicrobial agents represent the mainstay of treatment for diabetic foot infections,if peripheral arterial disease is present,revascularization should be considered to prevent limb amputation.A multidisciplinary approach to the prevention,diagnosis,and treatment of diabetic patients,including those with foot ulcers,is of the utmost importance to reduce the cost of treatment and avoid major adverse consequences such as amputation.展开更多
AIM:To evaluate the flipped classroom model for teaching horizontal strabismus didactics in an ophthalmology residency program in China as part of a visiting professorship from the United States.METHODS:Residents from...AIM:To evaluate the flipped classroom model for teaching horizontal strabismus didactics in an ophthalmology residency program in China as part of a visiting professorship from the United States.METHODS:Residents from an ophthalmology residency program in China were invited to participate in flipped classroom sessions taught by an experienced American ophthalmology faculty in 2018.Residents were instructed to watch a pre-class video lecture prior to the in-class-casebased activity.Content tests(5 Ophthalmic Knowledge Assessment Program style questions)and surveys were administered before and after the classroom sessions(100%response rate).These results were compared to that of an American cohort who were taught the same content.RESULTS:The Chinese cohort of 12 residents preferred the flipped classroom to the traditional classroom at higher rates than the American cohort of 40 residents(92%vs 55%,P=0.04)and felt that all ophthalmology topics would be appropriate for the flipped classroom teaching style(P-values between 0.008 and<0.001).In both Chinese and American cohorts,we found that the exotropia curriculum saw a small but significant improvement in performance following the flipped classroom session(P=0.025 for Chinese residents;P=0.001 for US residents),whereas scores in both groups for the esotropia course did not significantly improve.CONCLUSION:This is the first study to evaluate the flipped classroom model implemented by a visiting ophthalmology professor in a global outreach setting.The flipped classroom sessions are viewed favorably by the Chinese residents relative to the US cohort with a modest impact on knowledge.Decreased in-person interpreter requirement and increased student engagement make this model valuable in cross-cultural visiting professorship settings.Finally,the flipped classroom may lend itself well to a virtual format to prevent the transmission of COVID-19,although such a format requires further study.展开更多
The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independ...The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.展开更多
Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central...Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central in the pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI based on its role in decreasing oxidative stress,cytokine release,leukocyte endothelial-adhesion and hepatic apoptosis. This review will highlight the influence of endogenous NO on hepatic IRI,role of inhaled NO in ameliorating IRI,modes of delivery,donor drugs and potential side effects of exogenous NO.展开更多
Acute lower gastrointestinal bleeding(LGIB) is a frequent gastrointestinal cause of hospitalization,particularly in the elderly,and its incidence appears to be on the rise.Endoscopic and radiographic measures are avai...Acute lower gastrointestinal bleeding(LGIB) is a frequent gastrointestinal cause of hospitalization,particularly in the elderly,and its incidence appears to be on the rise.Endoscopic and radiographic measures are available for the evaluation and treatment of LGIB including flexible sigmoidoscopy,colonoscopy,angiography,radionuclide scintigraphy and multi-detector row computed tomography.Although no modality has emerged as the gold standard in the management of LGIB,colonoscopy is the current preferred initial test for the majority of the patients presenting with hematochezia felt to be from a colon source.Colonoscopy has the ability to diagnose all sources of bleeding from the colon and,unlike the radiologic modalities,does not require active bleeding at the time of the examination.In addition,therapeutic interventions such as cautery and endoclips can be applied to achieve hemostasis and prevent recurrent bleeding.Studies suggest that colonoscopy,particularly when performed early in the hospitalization,can decrease hospital length of stay,rebleeding and the need for surgery.However,results from available small trials are conflicting and larger,multicenter studies are needed.Compared to other management options,colonoscopy is a safe procedure with complications reported in less than 2% of patients,including those undergoing urgent examinations.The requirement of bowel preparation(typically 4 or more liters of polyethylene glycol),the logistical complexity of coordinating after-hours colonoscopy,and the low prevalence of stigmata of hemorrhage complicate the use of colonoscopy for LGIB,particularly in urgent situations.This review discusses the above advantages and disadvantages of colonoscopy in the management of acute lower gastrointestinal bleeding in further detail.展开更多
Hepatocyte nuclear factor 4-alpha(HNF4α)is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs(pancreas,stomach,a...Hepatocyte nuclear factor 4-alpha(HNF4α)is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs(pancreas,stomach,and intestine).In liver,HNF4αis best known for its role as a master regulator of liver-specific gene expression and essential for adult and fetal liver function.Dysregulation of HNF4αexpression has been associated with many human diseases such as ulcerative colitis,colon cancer,maturity-onset diabetes of the young,liver cirrhosis,and hepatocellular carcinoma.However,the precise role of HNF4αin the etiology of these human pathogenesis is not well understood.Limited information is known about the role of HNF4αisoforms in liver and gastrointestinal disease progression.There is,therefore,a critical need to know how disruption of the expression of these isoforms may impact on disease progression and phenotypes.In this review,we will update our current understanding on the role of HNF4αin human liver and gastrointestinal diseases.We further provide additional information on possible use of HNF4αas a target for potential therapeutic approaches.展开更多
Genetic polymorphisms in human genes can influence the risk for HIV-1 infection and disease progression, although the reported effects of these alleles have been inconsistent. This review highlights the recent discove...Genetic polymorphisms in human genes can influence the risk for HIV-1 infection and disease progression, although the reported effects of these alleles have been inconsistent. This review highlights the recent discoveries on global and Chinese genetic polymorphisms and their association with HIV-1 transmission and disease progression.展开更多
Anal intraepithelial neoplasia(AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the Unit...Anal intraepithelial neoplasia(AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus(HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPVmediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.展开更多
The first balloon angioplasty performed by Dr.Charles T.Dotter in 1964 marked the birth of a new discipline in radiology(1),which was initially named'interventional diagnostic radiology'by Dr.Alexander R.Margu...The first balloon angioplasty performed by Dr.Charles T.Dotter in 1964 marked the birth of a new discipline in radiology(1),which was initially named'interventional diagnostic radiology'by Dr.Alexander R.Margulis in 1967(2),and later defined as'Interventional Radiology(IR)'by Dr.Sidney Wallace in 1976(3).Along with the wide adaptation of Seldinger’s technique for percutaneous vascular access(4),interventional radiology expanded the horizon of traditional radiology.展开更多
Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prog...Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis.However,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose regimen.This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines.Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation.Indeed,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration.Implementing a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint selection.Strategies to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or tracking.Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin management.Finally,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies.展开更多
Hepatocellular carcinoma(HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks thir...Hepatocellular carcinoma(HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would:(1) greatly facilitate the identification of patients at risk;(2) prompt efforts to decrease risk factors; and(3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC,this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, noninvasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics.展开更多
Cancers are a concerning health catastrophe worldwide that may become the end of lifetime for many of us—they overwhelmingly exhaust medical resources,lead to huge economic burdens,and separate people from their belo...Cancers are a concerning health catastrophe worldwide that may become the end of lifetime for many of us—they overwhelmingly exhaust medical resources,lead to huge economic burdens,and separate people from their beloved ones.Fewer and fewer insurance agencies are willing to include primary cancers on their general health insurance plan,just because cancers have been so flummoxingly展开更多
Black raspberry(Rubus occidentalis L.)is a niche fruit crop valued for its flavor and potential health benefits.The improvement of fruit and cane characteristics via molecular breeding technologies has been hindered b...Black raspberry(Rubus occidentalis L.)is a niche fruit crop valued for its flavor and potential health benefits.The improvement of fruit and cane characteristics via molecular breeding technologies has been hindered by the lack of a high-quality reference genome.The recently released draft genome for black raspberry(ORUS 4115-3)lacks assembly of scaffolds to chromosome scale.We used high-throughput chromatin conformation capture(Hi-C)and Proximity-Guided Assembly(PGA)to cluster and order 9650 out of 11,936 contigs of this draft genome assembly into seven pseudo-chromosomes.The seven pseudo-chromosomes cover~97.2%of the total contig length(~223.8 Mb).Locating existing genetic markers on the physical map resolved multiple discrepancies in marker order on the genetic map.Centromeric regions were inferred from recombination frequencies of genetic markers,alignment of 303 bp centromeric sequence with the PGA,and heat map showing the physical contact matrix over the entire genome.We demonstrate a high degree of synteny between each of the seven chromosomes of black raspberry and a high-quality reference genome for strawberry(Fragaria vesca L.)assembled using only PacBio long-read sequences.We conclude that PGA is a cost-effective and rapid method of generating chromosome-scale assemblies from Illumina short-read sequencing data.展开更多
AIM To compare the prevalence of chronic liver disease(CLD) risk factors in a representative sample of MexicanAmericans born in the United States(US) or Mexico, to a sample of adults in Mexico.METHODS Data for Mexican...AIM To compare the prevalence of chronic liver disease(CLD) risk factors in a representative sample of MexicanAmericans born in the United States(US) or Mexico, to a sample of adults in Mexico.METHODS Data for Mexican-Americans in the US were obtained from the 1999-2014 National Health and Nutrition Examination Survey(NHANES), which includes persons of Mexican origin living in the US(n = 4274). The NHANES sample was restricted to Mexican-American participants who were 20 years and older, born in the US or Mexico, not pregnant or breastfeeding, and with medical insurance.The data in Mexico were obtained from the 2004-2013 Health Worker Cohort Study in Cuernavaca, Mexico(n =9485). The following known risk factors for liver disease/cancer were evaluated: elevated aminotransferase levels(elevated alanine aminotransferase was defined as > 40 IU/L for males and females; elevated aspartate aminotransferase was defined as > 40 IU/L for males and females), infection with hepatitis B or hepatitis C,metabolic syndrome, high total cholesterol, diabetes,obesity, abdominal obesity, and heavy alcohol use. The main independent variables for this study classified individuals by country of residence(i.e., Mexico vs the US) and place of birth(i.e., US-born vs Mexico-born).Regression analyses were used to investigate CLD risk factors.RESULTS After adjusting for socio-demographic characteristics,Mexican-American males were more likely to be obese,diabetic, heavy/binge drinkers or have abdominal obesity than males in Mexico. The adjusted multivariate results for females also indicate that Mexican-American females were significantly more likely to be obese, diabetic, be heavy/binge drinkers or have abdominal obesity than Mexican females. The prevalence ratios and prevalence differences mirror the multivariate analysis findings for the aforementioned risk factors, showing a greater risk among US-born as compared to Mexico-born MexicanAmericans. CONCLUSION In this study, Mexican-Americans in the US had more risk factors for CLD than their counterparts in Mexico.These findings can be used to design and implement more effective health promotion policies and programs to address the specific factors that put Mexicans at higher risk of developing CLD in both countries.展开更多
PURPOSE:To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated withconcurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost.METH-ODS ...PURPOSE:To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated withconcurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost.METH-ODS AND MATERIALS:Thirty-three patients with average risk(defined as<==1.5 cm(2)of residual tumorafter resection,age>3 years,and no involvement of the cerebrospinal fluid or spine)medulloblastoma werediagnosed at our institution between January 1994 and December 2001.They were enrolled in an institutional展开更多
Objective To examine the association of atherosclerosis burden in the survivors of an asymptomatic elderly cohort study and its relationship to other coronary risk factors (specifically, age) by evaluating aortic athe...Objective To examine the association of atherosclerosis burden in the survivors of an asymptomatic elderly cohort study and its relationship to other coronary risk factors (specifically, age) by evaluating aortic atherosclerotic wall burden by magnetic resonance imaging (MRI). Methods A total of 312 participants in an ongoing observational cohort study underwent cardiac and descending thoracic aorta imaging by MRI. Maximum wall thickness was measured and the mean wall thickness calculated.Wall/outer wall ratio was used as a normalized wall index (NWI) adjusted for artery size difference among participants. Percent wall volume (PWV) was calculated as NWI ×100.Results In this asymptomatic cohort (mean age: 76 years), the mean (SD) aortic wall area andwall thicknesswere 222 ±45 mm2 and 2.7 ±0.4 mm, respectively. Maximum wall thickness was 3.4 ±0.6 mm, and PWV was 32% ±4%. Women appeared to have smaller wall area,but after correcting for their smaller artery size, had significantly higher PWV than men (P = 0.03). Older age was associatedwith larger wall area (P = 0.04 for trend) with similar PWVs. However, there were no statistically significant associations between standard risk factors,Framingham global risk, or metabolic syndrome status, therapy for cholesterol or hypertension, coronary or aortic calcium score, and the aortic wall burden. Aortic calcificationwas associated with coronary calcification. Conclusions Asymptomatic elderly in this cohort had a greater descending thoracic aortic wall volume that correlated with age, andwomen had a significantly increased PWV compared to men. In these survivors, the atherosclerotic aortic wall burden was not significantly associated with traditional risk factors or with coronary or aortic calcium scores or coronary calcium progression. Results suggest that age, or as yet unidentified risk factor(s), may be responsible for the increase in atherosclerosis.展开更多
Background:To investigate the underlying molecular mechanisms of radiofrequency hyperthermia(RFH)-enhanced direct chemotherapy of pancreatic cancers.Method:Rat ductal PaCa cell line DSL-6A/C1 and orthotopic pancreatic...Background:To investigate the underlying molecular mechanisms of radiofrequency hyperthermia(RFH)-enhanced direct chemotherapy of pancreatic cancers.Method:Rat ductal PaCa cell line DSL-6A/C1 and orthotopic pancreatic cancers of Lewis rats were divided into four study groups with various treatments:i)phosphate-buffered saline(PBS)as a control;ii)RFH alone;iii)intratumoral chemotherapy alone(gemcitabine);and(iv)combination therapy of gemcitabine plus intratumoral RFH at 42°C for30 min.In the in-vitro confirmation experiments,the viability and apoptosis of DSL-6A/C1 cells in each treatment group were evaluated using cell live/dead staining,flow cytometry,and Western blot.In the in vivo validation experiments,related proteins were evaluated by immunohistochemistry(IHC)staining of tumors.Results:Of the in-vitro experiments,the lowest cell viability and more apoptotic cells were shown in the group with combination therapy compared to other treatments.Western blot data showed elevated Bax/Bcl-2,Caspase-3,and HSP70 expressions in DSL cells with combination therapy,compared to other treatments.Of the in vivo experiments,IHC staining detected the significantly increased expressions of HSP70,IL-1β,TNF-ɑ,Bax,and Caspase-3 in pancreatic cancer tissues of the animal group treated by combination therapy of gemcitabine with RFH.Conclusion:Molecular imaging-guided interventional RFH can significantly enhance the chemotherapeutic effect on pancreatic cancers via potential molecular mechanisms of up-regulating Bax/caspase-3-dependent apoptosis pathways.展开更多
Both diabetes and fungal infections contribute significantly to the global disease burden,with increasing trends seen in most developed and developing countries during recent decades.This is reflected in urogenital in...Both diabetes and fungal infections contribute significantly to the global disease burden,with increasing trends seen in most developed and developing countries during recent decades.This is reflected in urogenital infections caused by Candida species that are becoming ever more pervasive in diabetic patients,particularly those that present with unsatisfactory glycemic control.In addition,a relatively new group of anti-hyperglycemic drugs,known as sodium glucose cotransporter 2 inhibitors,has been linked with an increased risk for colonization of the urogenital region with Candida spp.,which can subsequently lead to an infectious process.In this review paper,we have highlighted notable virulence factors of Candida species(with an emphasis on Candida albicans)and shown how the interplay of many pathophysiological factors can give rise to vulvovaginal candidiasis,potentially complicated with recurrences and dire pregnancy outcomes.We have also addressed an increased risk of candiduria and urinary tract infections caused by species of Candida in females and males with diabetes,further highlighting possible complications such as emphysematous cystitis as well as the risk for the development of balanitis and balanoposthitis in(primarily uncircumcised)males.With a steadily increasing global burden of diabetes,urogenital mycotic infections will undoubtedly become more prevalent in the future;hence,there is a need for an evidence-based approach from both clinical and public health perspectives.展开更多
文摘Diabetes mellitus,a chronic disease of metabolism,is characterized by a disordered production or cellular utilization of insulin.Diabetic foot disease,which comprises the spectrum of infection,ulceration,and gangrene,is one of the most severe complications of diabetes and is the most common cause of hospitalization in diabetic patients.The aim of this study is to provide an evidence-based overview of diabetic foot complications.Due to neuropathy,diabetic foot infections can occur in the form of ulcers and minor skin lesions.In patients with diabetic foot ulcers,ischemia and infection are the main causes of non-healing ulcers and amputations.Hyperglycemia compromises the immune system of individuals with diabetes,leading to persistent inflammation and delayed wound healing.In addition,the treatment of diabetic foot infections is challenging due to difficulty in accurate identification of pathogenic microorganisms and the widespread issue of antimicrobial resistance.As a further complicating factor,the warning signs and symptoms of diabetic foot problems can easily be overlooked.Issues associated with diabetic foot complications include peripheral arterial disease and osteomyelitis;accordingly,the risk of these complications in people with diabetes should be assessed annually.Although antimicrobial agents represent the mainstay of treatment for diabetic foot infections,if peripheral arterial disease is present,revascularization should be considered to prevent limb amputation.A multidisciplinary approach to the prevention,diagnosis,and treatment of diabetic patients,including those with foot ulcers,is of the utmost importance to reduce the cost of treatment and avoid major adverse consequences such as amputation.
基金Supported by unrestricted grants from the National Institutes of Health CORE grant(No.EY001730)Research to Prevent Blindness to the University of Washington Department of Ophthalmology。
文摘AIM:To evaluate the flipped classroom model for teaching horizontal strabismus didactics in an ophthalmology residency program in China as part of a visiting professorship from the United States.METHODS:Residents from an ophthalmology residency program in China were invited to participate in flipped classroom sessions taught by an experienced American ophthalmology faculty in 2018.Residents were instructed to watch a pre-class video lecture prior to the in-class-casebased activity.Content tests(5 Ophthalmic Knowledge Assessment Program style questions)and surveys were administered before and after the classroom sessions(100%response rate).These results were compared to that of an American cohort who were taught the same content.RESULTS:The Chinese cohort of 12 residents preferred the flipped classroom to the traditional classroom at higher rates than the American cohort of 40 residents(92%vs 55%,P=0.04)and felt that all ophthalmology topics would be appropriate for the flipped classroom teaching style(P-values between 0.008 and<0.001).In both Chinese and American cohorts,we found that the exotropia curriculum saw a small but significant improvement in performance following the flipped classroom session(P=0.025 for Chinese residents;P=0.001 for US residents),whereas scores in both groups for the esotropia course did not significantly improve.CONCLUSION:This is the first study to evaluate the flipped classroom model implemented by a visiting ophthalmology professor in a global outreach setting.The flipped classroom sessions are viewed favorably by the Chinese residents relative to the US cohort with a modest impact on knowledge.Decreased in-person interpreter requirement and increased student engagement make this model valuable in cross-cultural visiting professorship settings.Finally,the flipped classroom may lend itself well to a virtual format to prevent the transmission of COVID-19,although such a format requires further study.
基金supported by the National Natural Science Foundation of China (82001372)National Key Research and Development Program of China (2018YFE0126700)+3 种基金Shanghai Jiao Tong University 2030 Initiative (WH510363001-7)Shanghai Municipal Commission of Science and Technology Program (21dz2210100)Shanghai Education Commission Research and Innovation Program (2019-01-07-00-02-E00037)a National Institutes of Health (NIH)grant (5R01HG002385)to E.E.E。
文摘The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.
文摘Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central in the pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI based on its role in decreasing oxidative stress,cytokine release,leukocyte endothelial-adhesion and hepatic apoptosis. This review will highlight the influence of endogenous NO on hepatic IRI,role of inhaled NO in ameliorating IRI,modes of delivery,donor drugs and potential side effects of exogenous NO.
文摘Acute lower gastrointestinal bleeding(LGIB) is a frequent gastrointestinal cause of hospitalization,particularly in the elderly,and its incidence appears to be on the rise.Endoscopic and radiographic measures are available for the evaluation and treatment of LGIB including flexible sigmoidoscopy,colonoscopy,angiography,radionuclide scintigraphy and multi-detector row computed tomography.Although no modality has emerged as the gold standard in the management of LGIB,colonoscopy is the current preferred initial test for the majority of the patients presenting with hematochezia felt to be from a colon source.Colonoscopy has the ability to diagnose all sources of bleeding from the colon and,unlike the radiologic modalities,does not require active bleeding at the time of the examination.In addition,therapeutic interventions such as cautery and endoclips can be applied to achieve hemostasis and prevent recurrent bleeding.Studies suggest that colonoscopy,particularly when performed early in the hospitalization,can decrease hospital length of stay,rebleeding and the need for surgery.However,results from available small trials are conflicting and larger,multicenter studies are needed.Compared to other management options,colonoscopy is a safe procedure with complications reported in less than 2% of patients,including those undergoing urgent examinations.The requirement of bowel preparation(typically 4 or more liters of polyethylene glycol),the logistical complexity of coordinating after-hours colonoscopy,and the low prevalence of stigmata of hemorrhage complicate the use of colonoscopy for LGIB,particularly in urgent situations.This review discusses the above advantages and disadvantages of colonoscopy in the management of acute lower gastrointestinal bleeding in further detail.
文摘Hepatocyte nuclear factor 4-alpha(HNF4α)is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs(pancreas,stomach,and intestine).In liver,HNF4αis best known for its role as a master regulator of liver-specific gene expression and essential for adult and fetal liver function.Dysregulation of HNF4αexpression has been associated with many human diseases such as ulcerative colitis,colon cancer,maturity-onset diabetes of the young,liver cirrhosis,and hepatocellular carcinoma.However,the precise role of HNF4αin the etiology of these human pathogenesis is not well understood.Limited information is known about the role of HNF4αisoforms in liver and gastrointestinal disease progression.There is,therefore,a critical need to know how disruption of the expression of these isoforms may impact on disease progression and phenotypes.In this review,we will update our current understanding on the role of HNF4αin human liver and gastrointestinal diseases.We further provide additional information on possible use of HNF4αas a target for potential therapeutic approaches.
文摘Genetic polymorphisms in human genes can influence the risk for HIV-1 infection and disease progression, although the reported effects of these alleles have been inconsistent. This review highlights the recent discoveries on global and Chinese genetic polymorphisms and their association with HIV-1 transmission and disease progression.
文摘Anal intraepithelial neoplasia(AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus(HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPVmediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.
文摘The first balloon angioplasty performed by Dr.Charles T.Dotter in 1964 marked the birth of a new discipline in radiology(1),which was initially named'interventional diagnostic radiology'by Dr.Alexander R.Margulis in 1967(2),and later defined as'Interventional Radiology(IR)'by Dr.Sidney Wallace in 1976(3).Along with the wide adaptation of Seldinger’s technique for percutaneous vascular access(4),interventional radiology expanded the horizon of traditional radiology.
文摘Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis.However,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose regimen.This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines.Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation.Indeed,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration.Implementing a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint selection.Strategies to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or tracking.Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin management.Finally,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies.
文摘Hepatocellular carcinoma(HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would:(1) greatly facilitate the identification of patients at risk;(2) prompt efforts to decrease risk factors; and(3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC,this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, noninvasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics.
文摘Cancers are a concerning health catastrophe worldwide that may become the end of lifetime for many of us—they overwhelmingly exhaust medical resources,lead to huge economic burdens,and separate people from their beloved ones.Fewer and fewer insurance agencies are willing to include primary cancers on their general health insurance plan,just because cancers have been so flummoxingly
文摘Black raspberry(Rubus occidentalis L.)is a niche fruit crop valued for its flavor and potential health benefits.The improvement of fruit and cane characteristics via molecular breeding technologies has been hindered by the lack of a high-quality reference genome.The recently released draft genome for black raspberry(ORUS 4115-3)lacks assembly of scaffolds to chromosome scale.We used high-throughput chromatin conformation capture(Hi-C)and Proximity-Guided Assembly(PGA)to cluster and order 9650 out of 11,936 contigs of this draft genome assembly into seven pseudo-chromosomes.The seven pseudo-chromosomes cover~97.2%of the total contig length(~223.8 Mb).Locating existing genetic markers on the physical map resolved multiple discrepancies in marker order on the genetic map.Centromeric regions were inferred from recombination frequencies of genetic markers,alignment of 303 bp centromeric sequence with the PGA,and heat map showing the physical contact matrix over the entire genome.We demonstrate a high degree of synteny between each of the seven chromosomes of black raspberry and a high-quality reference genome for strawberry(Fragaria vesca L.)assembled using only PacBio long-read sequences.We conclude that PGA is a cost-effective and rapid method of generating chromosome-scale assemblies from Illumina short-read sequencing data.
基金Supported by the Programa de Investigación en Migracion y Salud(PIMSA),No.2015-2106the Instituto Mexicano del Seguro Social(IMSS),No.2005/1/Ⅰ/093+2 种基金and the Consejo Nacional de Ciencia y Tecnología(CONACYT),No.26267MNo.SALUD-2011-01-161930the NIH,No.UL1TR000124 to Crespi CM,and NIH/NCI No.K07CA197179 to Flores YN
文摘AIM To compare the prevalence of chronic liver disease(CLD) risk factors in a representative sample of MexicanAmericans born in the United States(US) or Mexico, to a sample of adults in Mexico.METHODS Data for Mexican-Americans in the US were obtained from the 1999-2014 National Health and Nutrition Examination Survey(NHANES), which includes persons of Mexican origin living in the US(n = 4274). The NHANES sample was restricted to Mexican-American participants who were 20 years and older, born in the US or Mexico, not pregnant or breastfeeding, and with medical insurance.The data in Mexico were obtained from the 2004-2013 Health Worker Cohort Study in Cuernavaca, Mexico(n =9485). The following known risk factors for liver disease/cancer were evaluated: elevated aminotransferase levels(elevated alanine aminotransferase was defined as > 40 IU/L for males and females; elevated aspartate aminotransferase was defined as > 40 IU/L for males and females), infection with hepatitis B or hepatitis C,metabolic syndrome, high total cholesterol, diabetes,obesity, abdominal obesity, and heavy alcohol use. The main independent variables for this study classified individuals by country of residence(i.e., Mexico vs the US) and place of birth(i.e., US-born vs Mexico-born).Regression analyses were used to investigate CLD risk factors.RESULTS After adjusting for socio-demographic characteristics,Mexican-American males were more likely to be obese,diabetic, heavy/binge drinkers or have abdominal obesity than males in Mexico. The adjusted multivariate results for females also indicate that Mexican-American females were significantly more likely to be obese, diabetic, be heavy/binge drinkers or have abdominal obesity than Mexican females. The prevalence ratios and prevalence differences mirror the multivariate analysis findings for the aforementioned risk factors, showing a greater risk among US-born as compared to Mexico-born MexicanAmericans. CONCLUSION In this study, Mexican-Americans in the US had more risk factors for CLD than their counterparts in Mexico.These findings can be used to design and implement more effective health promotion policies and programs to address the specific factors that put Mexicans at higher risk of developing CLD in both countries.
文摘PURPOSE:To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated withconcurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost.METH-ODS AND MATERIALS:Thirty-three patients with average risk(defined as<==1.5 cm(2)of residual tumorafter resection,age>3 years,and no involvement of the cerebrospinal fluid or spine)medulloblastoma werediagnosed at our institution between January 1994 and December 2001.They were enrolled in an institutional
文摘Objective To examine the association of atherosclerosis burden in the survivors of an asymptomatic elderly cohort study and its relationship to other coronary risk factors (specifically, age) by evaluating aortic atherosclerotic wall burden by magnetic resonance imaging (MRI). Methods A total of 312 participants in an ongoing observational cohort study underwent cardiac and descending thoracic aorta imaging by MRI. Maximum wall thickness was measured and the mean wall thickness calculated.Wall/outer wall ratio was used as a normalized wall index (NWI) adjusted for artery size difference among participants. Percent wall volume (PWV) was calculated as NWI ×100.Results In this asymptomatic cohort (mean age: 76 years), the mean (SD) aortic wall area andwall thicknesswere 222 ±45 mm2 and 2.7 ±0.4 mm, respectively. Maximum wall thickness was 3.4 ±0.6 mm, and PWV was 32% ±4%. Women appeared to have smaller wall area,but after correcting for their smaller artery size, had significantly higher PWV than men (P = 0.03). Older age was associatedwith larger wall area (P = 0.04 for trend) with similar PWVs. However, there were no statistically significant associations between standard risk factors,Framingham global risk, or metabolic syndrome status, therapy for cholesterol or hypertension, coronary or aortic calcium score, and the aortic wall burden. Aortic calcificationwas associated with coronary calcification. Conclusions Asymptomatic elderly in this cohort had a greater descending thoracic aortic wall volume that correlated with age, andwomen had a significantly increased PWV compared to men. In these survivors, the atherosclerotic aortic wall burden was not significantly associated with traditional risk factors or with coronary or aortic calcium scores or coronary calcium progression. Results suggest that age, or as yet unidentified risk factor(s), may be responsible for the increase in atherosclerosis.
文摘Background:To investigate the underlying molecular mechanisms of radiofrequency hyperthermia(RFH)-enhanced direct chemotherapy of pancreatic cancers.Method:Rat ductal PaCa cell line DSL-6A/C1 and orthotopic pancreatic cancers of Lewis rats were divided into four study groups with various treatments:i)phosphate-buffered saline(PBS)as a control;ii)RFH alone;iii)intratumoral chemotherapy alone(gemcitabine);and(iv)combination therapy of gemcitabine plus intratumoral RFH at 42°C for30 min.In the in-vitro confirmation experiments,the viability and apoptosis of DSL-6A/C1 cells in each treatment group were evaluated using cell live/dead staining,flow cytometry,and Western blot.In the in vivo validation experiments,related proteins were evaluated by immunohistochemistry(IHC)staining of tumors.Results:Of the in-vitro experiments,the lowest cell viability and more apoptotic cells were shown in the group with combination therapy compared to other treatments.Western blot data showed elevated Bax/Bcl-2,Caspase-3,and HSP70 expressions in DSL cells with combination therapy,compared to other treatments.Of the in vivo experiments,IHC staining detected the significantly increased expressions of HSP70,IL-1β,TNF-ɑ,Bax,and Caspase-3 in pancreatic cancer tissues of the animal group treated by combination therapy of gemcitabine with RFH.Conclusion:Molecular imaging-guided interventional RFH can significantly enhance the chemotherapeutic effect on pancreatic cancers via potential molecular mechanisms of up-regulating Bax/caspase-3-dependent apoptosis pathways.
文摘Both diabetes and fungal infections contribute significantly to the global disease burden,with increasing trends seen in most developed and developing countries during recent decades.This is reflected in urogenital infections caused by Candida species that are becoming ever more pervasive in diabetic patients,particularly those that present with unsatisfactory glycemic control.In addition,a relatively new group of anti-hyperglycemic drugs,known as sodium glucose cotransporter 2 inhibitors,has been linked with an increased risk for colonization of the urogenital region with Candida spp.,which can subsequently lead to an infectious process.In this review paper,we have highlighted notable virulence factors of Candida species(with an emphasis on Candida albicans)and shown how the interplay of many pathophysiological factors can give rise to vulvovaginal candidiasis,potentially complicated with recurrences and dire pregnancy outcomes.We have also addressed an increased risk of candiduria and urinary tract infections caused by species of Candida in females and males with diabetes,further highlighting possible complications such as emphysematous cystitis as well as the risk for the development of balanitis and balanoposthitis in(primarily uncircumcised)males.With a steadily increasing global burden of diabetes,urogenital mycotic infections will undoubtedly become more prevalent in the future;hence,there is a need for an evidence-based approach from both clinical and public health perspectives.
