Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami taste.In this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alc...Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami taste.In this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alcoholic extracts of the oyster using nano-HPLC-MS/MS analysis,i Umami-Scoring Card Method(i Umami-SCM)database and molecular docking(MD).Sensory evaluation and electronic tongue analysis were further used to confirm their tastes.The threshold of the three peptides ranged from 0.38 to 0.55 mg/m L.MD with umami receptors T1R1/T1R3 indicated that the electrostatic interaction and hydrogen bond interaction were the main forces involved.Besides,the Phe592 and Gln853 of T1R3 were the primary docking site for MD and played an important role in umami intensity.Peptides with two Glu residues at the terminus had stronger umami,especially at the C-terminus.These results contribute to the understanding of umami peptides in oysters and the interaction mechanism between umami peptides and umami receptors.展开更多
Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechani...Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.展开更多
Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its...Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.展开更多
Point-of-care ultrasound(POCUS)of the internal jugular vein(IJV)offers a noninvasive means of estimating right atrial pressure(RAP),especially in cases where the inferior vena cava is inaccessible or unreliable due to...Point-of-care ultrasound(POCUS)of the internal jugular vein(IJV)offers a noninvasive means of estimating right atrial pressure(RAP),especially in cases where the inferior vena cava is inaccessible or unreliable due to conditions such as liver disease or abdominal surgery.While many clinicians are familiar with visually assessing jugular venous pressure through the internal jugular vein,this method lacks sensitivity.The utilization of POCUS significantly enhances the visualization of the vein,leading to a more accurate identification.It has been demonstrated that combining IJV POCUS with physical examination enhances the specificity of RAP estimation.This review aims to provide a comprehensive summary of the various sonographic techniques available for estimating RAP from the internal jugular vein,drawing upon existing data.展开更多
Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid increase in serum creatinine levels or a decrease in urine output or both.In spite of thorough history-taking,physical examination,and laboratory...Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid increase in serum creatinine levels or a decrease in urine output or both.In spite of thorough history-taking,physical examination,and laboratory analysis,there are limitations in the diagnostic process and clinical monitoring of AKI.Point-of-care ultrasonography(POCUS),a limited ultrasound study performed by clinicians at the bedside,has emerged as a valuable tool in different clinical settings.In this discussion,we explore the potential of POCUS performed by nephrologists to address specific questions encountered in the diagnosis and management of AKI patients.POCUS not only aids in excluding hydronephrosis but also provides real-time insights into hemodynamics,enabling formulation of individualized treatment plans.Further studies are required to assess the impact of multi-organ POCUS on pragmatic patient outcomes related to AKI,as well as its potential in risk stratification and identification of different levels of AKI severity and pathophysiological signatures.展开更多
Point of care ultrasonography(POCUS)is emerging as an invaluable tool for guiding patient care at the bedside,providing real-time diagnostic information to clinicians.Today,POCUS is recognized as the fifth pillar of b...Point of care ultrasonography(POCUS)is emerging as an invaluable tool for guiding patient care at the bedside,providing real-time diagnostic information to clinicians.Today,POCUS is recognized as the fifth pillar of bedside clinical examination,alongside inspection,palpation,percussion,and auscultation.In spite of growing interest,the adoption of diagnostic POCUS in nephrology remains limited,and comprehensive training beyond kidney ultrasound is offered in only a few fellowship programs.Moreover,several misconceptions and barriers surround the integration of POCUS into day-to-day nephrology practice.These include myths about its scope,utility,impact on patient outcomes and legal implications.In this minireview,we address some of these issues to encourage wider and proper utilization of POCUS.展开更多
This is an erratum to an already published paper.We found an error in the results section and Table 1.Specifically,we have revised results with n≤10 to be reflected as such,which is consistent with the reporting inst...This is an erratum to an already published paper.We found an error in the results section and Table 1.Specifically,we have revised results with n≤10 to be reflected as such,which is consistent with the reporting instructions by the Agency for Healthcare Research and Quality.Please note,these changes do not affect our results,and we had previously listed this requirement in the results section.We apologize for our unintentional mistake.展开更多
Introduction: Malaria is an important disease, causing high morbidity and mortality, especially in Sub-Saharan Africa. Measuring malaria prevalence using malaria rapid diagnostic tests (mRDTs), particularly among a vu...Introduction: Malaria is an important disease, causing high morbidity and mortality, especially in Sub-Saharan Africa. Measuring malaria prevalence using malaria rapid diagnostic tests (mRDTs), particularly among a vulnerable population sub-group, is a vital public health step in discovering effective methods of prevention and control. This study set out to examine the association between “place” and other risk factors with malaria prevalence among Batwa Indigenous People (IP). Methods: An analytical cross-sectional study design was implemented. Two surveys January 2014 (n = 572) and April 2014 (n = 541) involving interviews and testing for malaria using mRDTs were conducted in 10 Batwa settlements where a total of 1113 Batwa of all ages were surveyed and tested. The data were first compiled in MS Excel and then imported and analyzed using STATA ver.14. Descriptive statistics, were generated, followed by bivariable and multivariable regression model analysis to establish associations between the predictor and outcome variables with p ≤ 0.05 considered statistically significant. Results: Overall prevalence was 13.94% (n = 146). There is a significant relationship between settlement (place) and malaria prevalence AOR 11.7, 95% CI (1.38 - 98.93), p-value = 0.02. More males 16.97% (n = 84) tested positive compared to females 11.23% (n = 62) but there was no statistically significant association between gender and mRDT (p-value > 0.005). Children less than 5 years registered high prevalence and there was a significant relationship between age and mRDT (p-value ≤ 0.005). Wealth proxy indicators showed no association with prevalence p-value = 0.390. Season had no association with prevalence (p-value = 0.80). However, the proportion of the day spent in the forest/woodlands was significantly associated with malaria prevalence COR 12.83, 95% CI (1.14 - 143.73) p-value = 0.04. Low elevation was significantly associated with malaria prevalence COR 2.42, 95% CI (1.32 - 4.41), p = 0.004 but sleeping under a net and level of education did not show any association with malaria prevalence. Conclusion: This study highlights the importance of place in predicting malaria prevalence among Batwa Indigenous People a marginalized and remortely located sub-population. This study has shown that place matters in determining malaria prevalence. However, other factors like age, elevation and gender also contribute to malaria prevalence. Batwa have higher prevalence than the national and even non-indigenous populations in the same district. We recommend targeting hotspots intervention approach since it has proven reasonable impact on reducing malaria prevalence.展开更多
Congestive nephropathy is kidney dysfunction caused by the impact of elevated venous pressures on renal hemodynamics.As a part of cardiorenal syndrome,the diagnosis is usually made based on history and physical examin...Congestive nephropathy is kidney dysfunction caused by the impact of elevated venous pressures on renal hemodynamics.As a part of cardiorenal syndrome,the diagnosis is usually made based on history and physical examination,with findings such as jugular venous distension,a third heart sound,and vital signs as supporting findings.More recently,however,these once though objective measures have come under scrutiny for their accuracy.At the same time,bedside ultrasound has increased in popularity and is routinely being used by clinicians to take some of the guess work out of making the diagnosis of volume overload and venous congestion.In this mini-review,we will discuss some of the traditional methods used to measure venous congestion,describe the role of point-of-care ultrasound and how it can ameliorate a clinician’s evaluation,and offer a description of venous excess ultrasound score,a relatively novel scoring technique used to objectively quantify congestion.While there is a paucity of published large scale clinical trials evaluating the potential benefit of ultrasonography in venous congestion compared to gold standard invasive measurements,more study is underway to solidify the role of this objective measure in daily clinical practice.展开更多
INTRODUCTION Organoids are primary tissue or stem cells derived cell aggregates that have the capacity for self-organization,self-renewal,and the capacity to mimic cellular and tissue level functions.Organoids can ove...INTRODUCTION Organoids are primary tissue or stem cells derived cell aggregates that have the capacity for self-organization,self-renewal,and the capacity to mimic cellular and tissue level functions.Organoids can overcome the shortcomings of traditional 2D cell culture models and closely mimic 3D primary tissue composition.展开更多
Onco-Nephrology is an emerging subspecialty of Nephrology that focuses on a broad spectrum of renal disorders that can arise in patients with cancer.It encompasses acute kidney injury(AKI),complex fluid,electrolyte,an...Onco-Nephrology is an emerging subspecialty of Nephrology that focuses on a broad spectrum of renal disorders that can arise in patients with cancer.It encompasses acute kidney injury(AKI),complex fluid,electrolyte,and acid-base disorders,as well as chronic kidney disease caused or exacerbated by cancer and/or its treatment.In many such scenarios including AKI and hyponatremia,objective evaluation of hemodynamics is vital for appropriate management.Point of care ultrasonography(POCUS)is a limited ultrasound exam performed at the bedside and interpreted by the treating physician intended to answer focused clinical questions and guide therapy.Compared to conventional physical examination,POCUS offers substantially higher diagnostic accuracy for various structural and hemodynamic derangements.In this narrative review,we provide an overview of the utility of POCUS enhanced physical examination for the Onconephrologist supported by the current evidence and our experience-based opinion.展开更多
BACKGROUND The United States has witnessed significant advancements in the field of organ transplantation over the course of the last five decades,as demonstrated by a notable increase in the quantity of academic rese...BACKGROUND The United States has witnessed significant advancements in the field of organ transplantation over the course of the last five decades,as demonstrated by a notable increase in the quantity of academic research.The presence of a highly dynamic research environment necessitates continuous evaluations to maintain the integrity and progress of the field.AIM To evaluate the total output and thematic emphasis of transplant research conducted in the United States.METHODS On January 10,2023,we conducted a bibliometric search of United States research output in transplantation journals from the Web of Science database's Science Citation Index Expanded.We excluded editorials,meeting abstracts,and other non-article types.We analyzed annual trends,authors,institutions,articles,keywords,and countries collaborating with the United States,using VOSviewer 1.6.18 to create figures and tables.RESULTS The United States published 25956 papers(3078 reviews and 22878 articles)representing 37.7%of the world's scientific output.Canada emerged as the top collaborator with the United States,co-authoring 1263 articles.Leading institutions in United States transplantation research were the University of Pittsburgh(1749 articles),Mayo Clinic(1605 articles),Harvard Medical School(1549 articles),and Johns Hopkins University(1280 articles).The top three keywords with over 2000 occurrences were"recipients,""survival,"and"outcomes,"indicating a focus on graft and recipient outcome markers by United States researchers.CONCLUSION Our findings demonstrate the United States leadership in organ transplantation research,contributing significantly to the global scientific output in this field.However,opportunities exist for fostering expansive partnerships,particularly with developing countries.This study provides valuable insights into the transplantation research landscape in the United States,emphasizing the importance of ongoing evaluations to maintain and propel advancements in this critical medical discipline.The results may facilitate future collaborations,knowledge exchange,and the pursuit of innovative solutions in the realm of organ transplantation.展开更多
Background:Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion.Therefore,more accurate diagnostic markers are needed for sport-related co...Background:Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion.Therefore,more accurate diagnostic markers are needed for sport-related concussion.Methods:This was a multicenter,prospective,case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment,Research,and Education Consortium conducted between 2015 and 2019.The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints.Athletes with concussion were divided into 6 h post-injury(0-6 h post-injury)and after 6 h postinjury(7-48 h post-injury)groups.We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305proteins in plasma samples from athletes with and without sport-related concussion.Results:A total of 140 athletes with concussion(79.3%males;aged 18.71±1.10 years,mean±SD)and 21 non-concussed athletes(76.2%males;19.14±1.10 years)were included in this study.We identified 338 plasma proteins that significantly differed in abundance(319 upregulated and 19 downregulated)in concussed athletes compared to non-concussed athletes.The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve(AUC)of 0.954(95%confidence interval:0.922-0.986).Specifically,after 6 h of injury,the individual AUC of plasma erythrocyte membrane protein band 4.1(EPB41)and alpha-synuclein(SNCA)were 0.956 and 0.875,respectively.The combination of EPB41 and SNCA provided the best AUC(1.000),which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury.Conclusion:Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.展开更多
BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erl...BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.展开更多
Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting...Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting and the accumulation of the long chain fatty in the body. There are three types of CPT II deficiency, the myopathic form, the severe infantile hepatocardiomuscular form and the lethal neonatal form. They are all inherited as an autosomal recessive. Diagnosis of the CPTII are 1) tandem mass spectrometry (MS/MS) in adult form and 2) CPTII polymorphism (F352C), which is linked to reducing the activity of CPTII in infantile form [1]. Glucose is the primary management and medium-chain fatty acid is an alternative due to the bypass of the CPTII enzyme in the pathway. For the prevention of CPTII deficiency are to avoid long chain fatty acid (C12-fatty acid), fasting, prolonged exercise, known triggers, and certain medications such as anti-epileptics and general anesthesia. During the rhabdomyolysis and myoglobinuria attack, it is very important to maintain hydration to avoid acute renal failure. If, however, renal failure occurs, dialysis is recommended. We present a case of a 27-year-old African American woman with the significant past medical history of CPT II deficiency leading to recurrent rhabdomyolysis and myoglobinuria. Together with all the research studies from diagnosis to treatment of CPTII deficiency will help in clinical management of patients. And this case report will add to the existing case reports of patients who have CPTII deficiency in terms of how we diagnose, how we treat, and how we prevent symptoms from re-occurring.展开更多
Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur w...Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur without cirrhosis in NAFLD. Diabetes and obesity are associated risk factors for HCC in patients. Given the sheer magnitude of the underlying risk factors(diabetes, obesity, non-cirrhotic NAFLD) screening for HCC in the non-cirrhotic population is not recommended. Optimal screening strategies in NAFLD cirrhosis are not completely elucidated with Ultrasound having significant limitations in detection of liver lesions in the presence of obesity and steatosis. Consequently NAFLD-HCC is more often diagnosed at a later stage with larger tumors and reduced opportunities for curative treatments as opposed to HCC in other causes of cirrhosis. When HCC is found at a curative stage treatments including liver transplantation, resection and loco-regional therapies are associated with good results similar to that seen in HCV-HCC. Future strategies under study include the use of chemopreventive and antioxidant agents to reduce development of cirrhosis and non-alcoholic steatohepatitis(NASH). Strategies to reverse NASH via weight loss, control of associated conditions like diabetes are key strategies in reducing the increasing incidence of NASH-HCC. Novel therapeutic agents for NASH are in trials and if successful in achieving reversal of NASH will be an important strategy in reducing NAFLD-HCC.展开更多
Ghrelin causes interdigestive contractions of the stom- ach in rats. However, it remains unknown whether ghrelin causes interdigestive contractions in the small intestine. Four strain gauge transducers were implanted ...Ghrelin causes interdigestive contractions of the stom- ach in rats. However, it remains unknown whether ghrelin causes interdigestive contractions in the small intestine. Four strain gauge transducers were implanted on the antrum, duodenum, proximal and distal jejunum. After an overnight fast, gastrointestinal (GI) contrac- tions were recorded in freely moving conscious rats. Spontaneous phase Ⅲ-like contractions were observed at every 13-16 min in rat GI tract. The fasted motor patterns were replaced by the fed motor pattern immediately after food intake. Two minutes after f inishing the spontaneous phase Ⅲ-like contractions in the antrum, acyl ghrelin (0.8, 2.4 and 8.0 μg/kg per min) was con- tinuously infused for 30 min. Three-f ive minutes after the starting ghrelin infusion, augmented phase Ⅲ-like contractions were observed at the antrum, duodenum, and jejunum. Ghrelin infusion (0.8, 2.4 and 8.0 μg/kg per min) signif icantly increased motility index of phase Ⅲ-like contractions at the antrum and jejunum in a dose dependent manner, compared to that of saline in- jection. Thus, it is likely that exogenously administered ghrelin causes phase Ⅲ-like contraction at the antrum, which migrates to the duodenum and jejunum. The possible role of 5-HT, in addition to ghrelin, in mediating intestinal migrating motor complex (MMC), is discussed.展开更多
Type 2 diabetes(T2D) is the result of interaction between environmental factors and a strong hereditary component.We review the heritability of T2D as well as the history of genetic and genomic research in this area.V...Type 2 diabetes(T2D) is the result of interaction between environmental factors and a strong hereditary component.We review the heritability of T2D as well as the history of genetic and genomic research in this area.Very few T2D risk genes were identified using candidate gene and linkage-based studies,but the advent of genome-wide association studies has led to the identification of multiple genes,including several that were not previously known to play any role in T2D.Highly replicated genes,for example TCF7L2,KCNQ1 and KCNJ11,are discussed in greater detail.Taken together,the genetic loci discovered to date explain only a small proportion of the observed heritability.We discuss possible explanations for this "missing heritability",including the role of rare variants,gene-environment interactions and epigenetics.The clinical utility of current findings and avenues of future research are also discussed.展开更多
Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subseque...Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy.This study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.Methods:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were included.Patients who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT.Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.Results:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.001,0.016,and <0.001,respectively) and overall survival(HR = 3.50,2.32,and 4.34;95%CI 1.56-7.82,1.09-4.97,and 1.98-9.53;P = 0.002,0.030,and <0.001,respectively) in all patients.Conclusions:Testing for WTl transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission.A randomized study is warranted to determine whether allo-HSCT can improve prognosis in these patients.展开更多
Inflammatory bowel disease is a chronic,debilitating disorder of the gastrointestinal tract.The etiology of inflammatory bowel disease has not been elucidated,but is thought to be multifactorial with both environmenta...Inflammatory bowel disease is a chronic,debilitating disorder of the gastrointestinal tract.The etiology of inflammatory bowel disease has not been elucidated,but is thought to be multifactorial with both environmental and genetic influences.A large body of research has been conducted to elucidate the etiology of inflammatory bowel disease.This article reviews this literature,emphasizing the studies of breastfeeding and the studies of genetic factors,particularly NOD2 polymorphisms.展开更多
基金supported by the National Key Research and Development Program of China:Investigate the mechanism of formation and control technologies of Chinese traditional and ethnic food quality(2021YFD2100100)。
文摘Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami taste.In this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alcoholic extracts of the oyster using nano-HPLC-MS/MS analysis,i Umami-Scoring Card Method(i Umami-SCM)database and molecular docking(MD).Sensory evaluation and electronic tongue analysis were further used to confirm their tastes.The threshold of the three peptides ranged from 0.38 to 0.55 mg/m L.MD with umami receptors T1R1/T1R3 indicated that the electrostatic interaction and hydrogen bond interaction were the main forces involved.Besides,the Phe592 and Gln853 of T1R3 were the primary docking site for MD and played an important role in umami intensity.Peptides with two Glu residues at the terminus had stronger umami,especially at the C-terminus.These results contribute to the understanding of umami peptides in oysters and the interaction mechanism between umami peptides and umami receptors.
基金supported by grants R01 GM112696 and 1R35GM148177 from the National Institutes of Health(to XB)Advancing a Healthier Wisconsin(to XB)Medical College of Wisconsin-Neuroscience Research Center-Alzheimer’s Award(to XB).
文摘Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.
文摘Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.
文摘Point-of-care ultrasound(POCUS)of the internal jugular vein(IJV)offers a noninvasive means of estimating right atrial pressure(RAP),especially in cases where the inferior vena cava is inaccessible or unreliable due to conditions such as liver disease or abdominal surgery.While many clinicians are familiar with visually assessing jugular venous pressure through the internal jugular vein,this method lacks sensitivity.The utilization of POCUS significantly enhances the visualization of the vein,leading to a more accurate identification.It has been demonstrated that combining IJV POCUS with physical examination enhances the specificity of RAP estimation.This review aims to provide a comprehensive summary of the various sonographic techniques available for estimating RAP from the internal jugular vein,drawing upon existing data.
文摘Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid increase in serum creatinine levels or a decrease in urine output or both.In spite of thorough history-taking,physical examination,and laboratory analysis,there are limitations in the diagnostic process and clinical monitoring of AKI.Point-of-care ultrasonography(POCUS),a limited ultrasound study performed by clinicians at the bedside,has emerged as a valuable tool in different clinical settings.In this discussion,we explore the potential of POCUS performed by nephrologists to address specific questions encountered in the diagnosis and management of AKI patients.POCUS not only aids in excluding hydronephrosis but also provides real-time insights into hemodynamics,enabling formulation of individualized treatment plans.Further studies are required to assess the impact of multi-organ POCUS on pragmatic patient outcomes related to AKI,as well as its potential in risk stratification and identification of different levels of AKI severity and pathophysiological signatures.
文摘Point of care ultrasonography(POCUS)is emerging as an invaluable tool for guiding patient care at the bedside,providing real-time diagnostic information to clinicians.Today,POCUS is recognized as the fifth pillar of bedside clinical examination,alongside inspection,palpation,percussion,and auscultation.In spite of growing interest,the adoption of diagnostic POCUS in nephrology remains limited,and comprehensive training beyond kidney ultrasound is offered in only a few fellowship programs.Moreover,several misconceptions and barriers surround the integration of POCUS into day-to-day nephrology practice.These include myths about its scope,utility,impact on patient outcomes and legal implications.In this minireview,we address some of these issues to encourage wider and proper utilization of POCUS.
文摘This is an erratum to an already published paper.We found an error in the results section and Table 1.Specifically,we have revised results with n≤10 to be reflected as such,which is consistent with the reporting instructions by the Agency for Healthcare Research and Quality.Please note,these changes do not affect our results,and we had previously listed this requirement in the results section.We apologize for our unintentional mistake.
文摘Introduction: Malaria is an important disease, causing high morbidity and mortality, especially in Sub-Saharan Africa. Measuring malaria prevalence using malaria rapid diagnostic tests (mRDTs), particularly among a vulnerable population sub-group, is a vital public health step in discovering effective methods of prevention and control. This study set out to examine the association between “place” and other risk factors with malaria prevalence among Batwa Indigenous People (IP). Methods: An analytical cross-sectional study design was implemented. Two surveys January 2014 (n = 572) and April 2014 (n = 541) involving interviews and testing for malaria using mRDTs were conducted in 10 Batwa settlements where a total of 1113 Batwa of all ages were surveyed and tested. The data were first compiled in MS Excel and then imported and analyzed using STATA ver.14. Descriptive statistics, were generated, followed by bivariable and multivariable regression model analysis to establish associations between the predictor and outcome variables with p ≤ 0.05 considered statistically significant. Results: Overall prevalence was 13.94% (n = 146). There is a significant relationship between settlement (place) and malaria prevalence AOR 11.7, 95% CI (1.38 - 98.93), p-value = 0.02. More males 16.97% (n = 84) tested positive compared to females 11.23% (n = 62) but there was no statistically significant association between gender and mRDT (p-value > 0.005). Children less than 5 years registered high prevalence and there was a significant relationship between age and mRDT (p-value ≤ 0.005). Wealth proxy indicators showed no association with prevalence p-value = 0.390. Season had no association with prevalence (p-value = 0.80). However, the proportion of the day spent in the forest/woodlands was significantly associated with malaria prevalence COR 12.83, 95% CI (1.14 - 143.73) p-value = 0.04. Low elevation was significantly associated with malaria prevalence COR 2.42, 95% CI (1.32 - 4.41), p = 0.004 but sleeping under a net and level of education did not show any association with malaria prevalence. Conclusion: This study highlights the importance of place in predicting malaria prevalence among Batwa Indigenous People a marginalized and remortely located sub-population. This study has shown that place matters in determining malaria prevalence. However, other factors like age, elevation and gender also contribute to malaria prevalence. Batwa have higher prevalence than the national and even non-indigenous populations in the same district. We recommend targeting hotspots intervention approach since it has proven reasonable impact on reducing malaria prevalence.
文摘Congestive nephropathy is kidney dysfunction caused by the impact of elevated venous pressures on renal hemodynamics.As a part of cardiorenal syndrome,the diagnosis is usually made based on history and physical examination,with findings such as jugular venous distension,a third heart sound,and vital signs as supporting findings.More recently,however,these once though objective measures have come under scrutiny for their accuracy.At the same time,bedside ultrasound has increased in popularity and is routinely being used by clinicians to take some of the guess work out of making the diagnosis of volume overload and venous congestion.In this mini-review,we will discuss some of the traditional methods used to measure venous congestion,describe the role of point-of-care ultrasound and how it can ameliorate a clinician’s evaluation,and offer a description of venous excess ultrasound score,a relatively novel scoring technique used to objectively quantify congestion.While there is a paucity of published large scale clinical trials evaluating the potential benefit of ultrasonography in venous congestion compared to gold standard invasive measurements,more study is underway to solidify the role of this objective measure in daily clinical practice.
文摘INTRODUCTION Organoids are primary tissue or stem cells derived cell aggregates that have the capacity for self-organization,self-renewal,and the capacity to mimic cellular and tissue level functions.Organoids can overcome the shortcomings of traditional 2D cell culture models and closely mimic 3D primary tissue composition.
文摘Onco-Nephrology is an emerging subspecialty of Nephrology that focuses on a broad spectrum of renal disorders that can arise in patients with cancer.It encompasses acute kidney injury(AKI),complex fluid,electrolyte,and acid-base disorders,as well as chronic kidney disease caused or exacerbated by cancer and/or its treatment.In many such scenarios including AKI and hyponatremia,objective evaluation of hemodynamics is vital for appropriate management.Point of care ultrasonography(POCUS)is a limited ultrasound exam performed at the bedside and interpreted by the treating physician intended to answer focused clinical questions and guide therapy.Compared to conventional physical examination,POCUS offers substantially higher diagnostic accuracy for various structural and hemodynamic derangements.In this narrative review,we provide an overview of the utility of POCUS enhanced physical examination for the Onconephrologist supported by the current evidence and our experience-based opinion.
文摘BACKGROUND The United States has witnessed significant advancements in the field of organ transplantation over the course of the last five decades,as demonstrated by a notable increase in the quantity of academic research.The presence of a highly dynamic research environment necessitates continuous evaluations to maintain the integrity and progress of the field.AIM To evaluate the total output and thematic emphasis of transplant research conducted in the United States.METHODS On January 10,2023,we conducted a bibliometric search of United States research output in transplantation journals from the Web of Science database's Science Citation Index Expanded.We excluded editorials,meeting abstracts,and other non-article types.We analyzed annual trends,authors,institutions,articles,keywords,and countries collaborating with the United States,using VOSviewer 1.6.18 to create figures and tables.RESULTS The United States published 25956 papers(3078 reviews and 22878 articles)representing 37.7%of the world's scientific output.Canada emerged as the top collaborator with the United States,co-authoring 1263 articles.Leading institutions in United States transplantation research were the University of Pittsburgh(1749 articles),Mayo Clinic(1605 articles),Harvard Medical School(1549 articles),and Johns Hopkins University(1280 articles).The top three keywords with over 2000 occurrences were"recipients,""survival,"and"outcomes,"indicating a focus on graft and recipient outcome markers by United States researchers.CONCLUSION Our findings demonstrate the United States leadership in organ transplantation research,contributing significantly to the global scientific output in this field.However,opportunities exist for fostering expansive partnerships,particularly with developing countries.This study provides valuable insights into the transplantation research landscape in the United States,emphasizing the importance of ongoing evaluations to maintain and propel advancements in this critical medical discipline.The results may facilitate future collaborations,knowledge exchange,and the pursuit of innovative solutions in the realm of organ transplantation.
基金supported by the Grand Alliance CARE Consortiumfunded in part by the National Collegiate Athletic Association(NCAA)+1 种基金the Department of Defense(DoD).supported by the Office of the Assistant Secretary of Defense for Health Affairs,through the Combat Casualty Care Research Program,endorsed by the Department of Defense,under Award No.W81XWH1420151。
文摘Background:Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion.Therefore,more accurate diagnostic markers are needed for sport-related concussion.Methods:This was a multicenter,prospective,case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment,Research,and Education Consortium conducted between 2015 and 2019.The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints.Athletes with concussion were divided into 6 h post-injury(0-6 h post-injury)and after 6 h postinjury(7-48 h post-injury)groups.We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305proteins in plasma samples from athletes with and without sport-related concussion.Results:A total of 140 athletes with concussion(79.3%males;aged 18.71±1.10 years,mean±SD)and 21 non-concussed athletes(76.2%males;19.14±1.10 years)were included in this study.We identified 338 plasma proteins that significantly differed in abundance(319 upregulated and 19 downregulated)in concussed athletes compared to non-concussed athletes.The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve(AUC)of 0.954(95%confidence interval:0.922-0.986).Specifically,after 6 h of injury,the individual AUC of plasma erythrocyte membrane protein band 4.1(EPB41)and alpha-synuclein(SNCA)were 0.956 and 0.875,respectively.The combination of EPB41 and SNCA provided the best AUC(1.000),which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury.Conclusion:Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.
基金Supported by NIH/National Cancer Institute Grant,No.R01CA138441 and No.R01CA269452UW Madison Centene Pancreas Cancer Collaborative Award,No.21-8568.
文摘BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.
文摘Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting and the accumulation of the long chain fatty in the body. There are three types of CPT II deficiency, the myopathic form, the severe infantile hepatocardiomuscular form and the lethal neonatal form. They are all inherited as an autosomal recessive. Diagnosis of the CPTII are 1) tandem mass spectrometry (MS/MS) in adult form and 2) CPTII polymorphism (F352C), which is linked to reducing the activity of CPTII in infantile form [1]. Glucose is the primary management and medium-chain fatty acid is an alternative due to the bypass of the CPTII enzyme in the pathway. For the prevention of CPTII deficiency are to avoid long chain fatty acid (C12-fatty acid), fasting, prolonged exercise, known triggers, and certain medications such as anti-epileptics and general anesthesia. During the rhabdomyolysis and myoglobinuria attack, it is very important to maintain hydration to avoid acute renal failure. If, however, renal failure occurs, dialysis is recommended. We present a case of a 27-year-old African American woman with the significant past medical history of CPT II deficiency leading to recurrent rhabdomyolysis and myoglobinuria. Together with all the research studies from diagnosis to treatment of CPTII deficiency will help in clinical management of patients. And this case report will add to the existing case reports of patients who have CPTII deficiency in terms of how we diagnose, how we treat, and how we prevent symptoms from re-occurring.
文摘Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur without cirrhosis in NAFLD. Diabetes and obesity are associated risk factors for HCC in patients. Given the sheer magnitude of the underlying risk factors(diabetes, obesity, non-cirrhotic NAFLD) screening for HCC in the non-cirrhotic population is not recommended. Optimal screening strategies in NAFLD cirrhosis are not completely elucidated with Ultrasound having significant limitations in detection of liver lesions in the presence of obesity and steatosis. Consequently NAFLD-HCC is more often diagnosed at a later stage with larger tumors and reduced opportunities for curative treatments as opposed to HCC in other causes of cirrhosis. When HCC is found at a curative stage treatments including liver transplantation, resection and loco-regional therapies are associated with good results similar to that seen in HCV-HCC. Future strategies under study include the use of chemopreventive and antioxidant agents to reduce development of cirrhosis and non-alcoholic steatohepatitis(NASH). Strategies to reverse NASH via weight loss, control of associated conditions like diabetes are key strategies in reducing the increasing incidence of NASH-HCC. Novel therapeutic agents for NASH are in trials and if successful in achieving reversal of NASH will be an important strategy in reducing NAFLD-HCC.
文摘Ghrelin causes interdigestive contractions of the stom- ach in rats. However, it remains unknown whether ghrelin causes interdigestive contractions in the small intestine. Four strain gauge transducers were implanted on the antrum, duodenum, proximal and distal jejunum. After an overnight fast, gastrointestinal (GI) contrac- tions were recorded in freely moving conscious rats. Spontaneous phase Ⅲ-like contractions were observed at every 13-16 min in rat GI tract. The fasted motor patterns were replaced by the fed motor pattern immediately after food intake. Two minutes after f inishing the spontaneous phase Ⅲ-like contractions in the antrum, acyl ghrelin (0.8, 2.4 and 8.0 μg/kg per min) was con- tinuously infused for 30 min. Three-f ive minutes after the starting ghrelin infusion, augmented phase Ⅲ-like contractions were observed at the antrum, duodenum, and jejunum. Ghrelin infusion (0.8, 2.4 and 8.0 μg/kg per min) signif icantly increased motility index of phase Ⅲ-like contractions at the antrum and jejunum in a dose dependent manner, compared to that of saline in- jection. Thus, it is likely that exogenously administered ghrelin causes phase Ⅲ-like contraction at the antrum, which migrates to the duodenum and jejunum. The possible role of 5-HT, in addition to ghrelin, in mediating intestinal migrating motor complex (MMC), is discussed.
文摘Type 2 diabetes(T2D) is the result of interaction between environmental factors and a strong hereditary component.We review the heritability of T2D as well as the history of genetic and genomic research in this area.Very few T2D risk genes were identified using candidate gene and linkage-based studies,but the advent of genome-wide association studies has led to the identification of multiple genes,including several that were not previously known to play any role in T2D.Highly replicated genes,for example TCF7L2,KCNQ1 and KCNJ11,are discussed in greater detail.Taken together,the genetic loci discovered to date explain only a small proportion of the observed heritability.We discuss possible explanations for this "missing heritability",including the role of rare variants,gene-environment interactions and epigenetics.The clinical utility of current findings and avenues of future research are also discussed.
基金supported by Grants from the Key Program of the National Natural Science Foundation of China(81230013)the Major State Basic Research Development Program of China(973 Program,2013CB733701)+2 种基金the Nature Science Foundation of China(81170483,81570130 and 81370639)the Beijing Municipal Science and Technology Commission(Z141100000214011)support from the NIHR Biomedical Research Centre funding scheme
文摘Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy.This study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.Methods:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were included.Patients who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT.Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.Results:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.001,0.016,and <0.001,respectively) and overall survival(HR = 3.50,2.32,and 4.34;95%CI 1.56-7.82,1.09-4.97,and 1.98-9.53;P = 0.002,0.030,and <0.001,respectively) in all patients.Conclusions:Testing for WTl transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission.A randomized study is warranted to determine whether allo-HSCT can improve prognosis in these patients.
文摘Inflammatory bowel disease is a chronic,debilitating disorder of the gastrointestinal tract.The etiology of inflammatory bowel disease has not been elucidated,but is thought to be multifactorial with both environmental and genetic influences.A large body of research has been conducted to elucidate the etiology of inflammatory bowel disease.This article reviews this literature,emphasizing the studies of breastfeeding and the studies of genetic factors,particularly NOD2 polymorphisms.
