Simultaneous Compression of the Celiac Trunk, Superior Mesenteric Artery, and Renal Arteries by the Median Arcuate Ligament: About One Case

Median arcuate ligament syndrome (MALS), is a rare abdominal vascular compression syndrome caused by the compression of the proximal celiac trunk by the median arcuate ligament. According to many authors, a low insertion of the diaphragmatic crura or an abnormally high origin of the celiac trunk from the aorta can cause compression of the celiac artery. Usually, patients with MALS are asymptomatic. Computed tomography (CT) angiography of the abdomen is the main imaging modality to confirm the diagnosis. The coexistence of celiac trunk and superior mesenteric artery compression by the median arcuate ligament is rarely described in the literature. To our knowledge, until now, a simultaneous combination of three abdominal vascular compressions by the median arcuate ligament has never been described. From this case, we report a simultaneous compression of the celiac trunk, superior mesenteric artery, and renal arteries by the median arcuate ligament.

An Anatomical and Radiological Study of Origins of the Arteries Forming the Celiac Trunk: Clinical and Embryological Implications

The blood supply to the most of abdominal organs is provided by the branches of CT. The SMA supply caecum, ascends colon, all of the small bowels except the upper part of duodenum. Knowledge of variable anatomy of celiac axis and SMA may be useful in planning and executing radiological interventions such as celiacography and chemoembolization of hepatic and pancreatic tumors. In this study, the uncommon or low percentage cases of CT and SMA are presented in the light of clinical and embryological information. The celiac axises of a total of 30 adult corpses were examined. Dissections of abdominal region were performed in detail according to Cunningham’s manual. Angiographic images of 100 consecutive adult patients who underwent celiac MDCT angiography were evaluated. During autopsies, an incomplete celiac trunk or bifurcation of celiac trunk associated with the hepatomesenteric and gastrosplenic trunks (0.7%) and a celiacomesenteric trunk associated with high origin superior mesenteric artery and gastrosplenic trunk were detected (0.7%). During MDCT angiography, a case of total absence of celiac trunk associated with a hepatosplenomesenteric trunk (0.7%) and also a case of total absence of celiac trunk alone were observed (0.7%). The persistence or unusual development of ventral splanchnic arteries (VSAs) or ventral longitudinal anastomosis may result in variations or the unusual trunks related to celiac axis and SMA. The anomalous trunks of the CT may be result of either the persistence of some parts of the VSAs or ventral longitudinal anastomose that normally disappear or disappearance of parts that normally persist. The prevalence of unusual trunks of celiac axis and SMA in this study is quite low in literature. These abnormal vessels pose problems for surgeons and radiologists. Such vascular anomalies may cause clinical complications following surgical and radiological procedures such as resection of tumor of the pancreatic head, lymphadenectomy, coeliacography, aortic replacement with reimplantation of the trunk and coembolization of pancreatic and liver tumors.

Case Report: Surgical Correction of Transposition of the Great Arteries with Aortopulmonary Window

Introduction:Transposition of the great arteries(TGA)with aortopulmonary window is a rare type of congenital heart disease with limited experience.We reported a neonate aged 25 days receiving the arterial switch operation and assisted with extracorporeal membrane oxygenation.Conclusion:TGA with aortopulmonary window can be safely correctly with the arterial switch operation.

Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm,further clinical research is warranted.

Relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine fetal distress

BACKGROUND By comprehensively analyzing the blood flow parameters of the umbilical and middle cerebral arteries,doctors can more accurately identify fetal intrauterine distress,as well as assess its severity,so that timely interventions can be implemented to safeguard the health and safety of the fetus.AIM To identify the relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine distress.METHODS Clinical data of pregnant women admitted between January 2021 and January 2023 were collected and divided into the observation and control groups(n=50 each),according to the presence or absence of intrauterine distress.The ultrasound hemodynamic parameters of the uterine artery(UtA),fetal middle cerebral artery(MCA),and umbilical artery(UmA)were compared with neonatal outcomes and occurrence of intrauterine distress in the two groups.RESULTS Comparison of ultrasonic hemodynamic parameters,resistance index(RI),pulsatility index(PI),and systolic maximal blood flow velocity of UmA compared to diastolic blood flow velocity(S/D),revealed higher values of fetal MCA,PI,and S/D of UmA in pregnant women with UtA compared to controls(P<0.05),while there was no difference between the two groups in terms of RI(P<0.05)The incidence of a neonatal Apgar score of 8-10 points was lower in the observation group(66.7%)than in the control group(90.0%),and neonatal weight(2675.5±27.6 g)was lower than in the control group(3117.5±31.2 g).Further,cesarean section rate was higher in the observation group(70.0%)than in the control group(11.7%),and preterm labor rate was higher in the observation group(40.0%)than in the control group(10.0%).The incidence of fetal distress,neonatal growth restriction and neonatal asphyxia were also higher in the observation group(all P<0.05).CONCLUSION Fetal MCA,UmA,and maternal UtA hemodynamic abnormalities all develop in pregnant women with intrauterine distress during late pregnancy,which suggests that clinical attention should be paid to them,and monitoring should be strengthened to provide guidance for clinical intervention.

Digesting gluten with oral endopeptidases to improve the management of celiac disease

In our editorial,we want to comment on the article by Stefanolo et al titled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”.Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals.Although avoiding gluten can permit patients to live symptom-free,ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel mucosa.As villous atrophy predisposes patients to life threatening complications,such as osteoporotic fractures or malignancies,therapeutic adjuncts to gluten-free diet become important to improve patients’quality of life and,if these adjuncts can be shown to improve villous atrophy,avoid complications.Oral administration of enzyme preparations,such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflam-mation,is one clinical strategy under investigation.The article is about the utility of one endopeptidase isolated from Aspergillus niger.We critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.

Aspergillus niger prolyl endopeptidase in celiac disease

We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroenterology.Celiac disease is a well-recognized systemic autoimmune disorder.In genetically susceptible people,the most evident damage is located in the small intestine,and is caused and worsened by the ingestion of gluten.For that reason,celiac patients adopt a gluten-free diet(GFD),but it has some limitations,and it does not prevent re-exposure to gluten.Research aims to develop adjuvant therapies,and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease(AN-PEP),which is able to degrade gluten in the stomach,reducing its concentration in the small intestine.The study found a high adherence to the GFD,but did not address AN-PEP as a gluten immunogenic peptide reducer,as it was only tested in patients following a GFD and not in gluten-exposing conditions.This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.

Advances in understanding and managing celiac disease:Pathophysiology and treatment strategies

In this editorial,we comment on an article published in the recent issue of the World Journal of Gastroenterology.Celiac disease(CeD)is a disease occurring in genetically susceptible individuals,which is mainly characterized by gluten intolerance in the small intestine and clinical symptoms such as abdominal pain,diarrhea,and malnutrition.Therefore,patients often need a lifelong gluten-free diet,which greatly affects the quality of life and expenses of patients.The gold standard for diagnosis is intestinal mucosal biopsy,combined with serological and genetic tests.At present,the lack of safe,effective,and satisfactory drugs for CeD is mainly due to the complexity of its pathogenesis,and it is difficult to find a perfect target to solve the multi-level needs of patients.In this editorial,we mainly review the pathological mechanism of CeD and describe the current experimental and improved drugs for various pathological aspects.

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

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

Beyond the gluten-free diet:Innovations in celiac disease therapeutics

Celiac disease(CD)is an autoimmune disorder exacerbated by the ingestion of gluten in genetically susceptible individuals,leading to intestinal inflammation and damage.This chronic disease affects approximately 1%of the world’s po-pulation and is a growing health challenge due to its increasing prevalence.The development of CD is a complex interaction between genetic predispositions and environmental factors,especially gluten,culminating in a dysregulated immune response.The only effective treatment at present is a strict,lifelong gluten-free diet.However,adherence to this diet is challenging and often incomplete,so research into alternative therapies has intensified.Recent advances in under-standing the molecular and immunological aspects of CD have spearheaded the development of novel pharmacologic strategies that should provide more effec-tive and manageable treatment options.This review examines the latest inno-vations in CD therapies.The focus is on drugs in advanced clinical phases and targeting specific signaling pathways critical to the disease pathogenesis.We dis-cuss both quantitative strategies such as enzymatic degradation of gluten,and qualitative approaches including immunomodulation and induction of gluten tolerance.Innovative treatments currently under investigation include transglu-taminase inhibitors,which prevent the modification of gluten peptides,and nano-particle-based therapies to recalibrate the immune response.These new therapies not only promise to improve patient outcomes but are also expected to improve quality of life by reducing the burden of dietary restrictions.The integration of these new therapies could revolutionize the treatment of CD and shift the para-digm from strict dietary restrictions to a more flexible and patient-friendly thera-peutic approach.This review provides a comprehensive overview of the future prospects of CD treatment and emphasizes the importance of continued research and multidisciplinary collab-oration to integrate these advances into standard clinical practice.

Prevalence of malignant neoplasms in celiac disease patients-a nationwide United States population-based study

BACKGROUND Celiac disease(CeD)is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals.Recent research has unveiled a heightened risk of developing specific malignant neoplasms(MN)and various malignancies,including gastrointestinal,lymphomas,skin,and others,in individuals with CeD.AIM To investigate the prevalence of MN in hospitalized CeD patients in the United States.METHODS Using data from the National Inpatient Sample spanning two decades,from January 2000 to December 2019,we identified 529842 CeD patients,of which 78128(14.75%)had MN.Propensity score matching,based on age,sex,race,and calendar year,was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio.RESULTS Positive associations were observed for several malignancies,including small intestine,lymphoma,nonmelanoma skin,liver,melanoma skin,pancreas myelodysplastic syndrome,biliary,stomach,and other neuroendocrine tumors(excluding small and large intestine malignant carcinoid),leukemia,uterus,and testis.Conversely,CeD patients exhibited a reduced risk of respiratory and secondary malignancies.Moreover,certain malignancies showed null associations with CeD,including head and neck,nervous system,esophagus,colorectal,anus,breast,malignant carcinoids,bone and connective tissues,myeloma,cervix,and ovary cancers.CONCLUSION Our study is unique in highlighting the detailed results of positive,negative,or null associations between different hematologic and solid malignancies and CeD.Furthermore,it offers insights into evolving trends in CeD hospital outcomes,shedding light on advancements in its management over the past two decades.These findings contribute valuable information to the understanding of CeD’s impact on health and healthcare utilization.

High Prevalence of Anatomical Variations and Anomalies of the Coronary Arteries Detected by CT Angiography in Symptomatic Patients

Objective:Coronary artery anatomical variations and anomalies are an important topic due to their potential clinical manifestations.This study aims to investigate the prevalence of coronary artery anatomical variations and anomalies in symptomatic patients with coronary computed tomography angiography(CCTA).Methods:This is a retrospective study that included all symptomatic patients who had CCTA in a tertiary care hospital in Saudi Arabia during a period of seven years.Results:The total number of included patients was 507(60%males)with a mean age of 57.4 years.Approximately 41%had luminal stenoses,averaging 49.7%.The total num-ber of patients with coronary anatomical variations(CAV)and coronary artery anomalies(CAA)was 217(43%).CAV prevalence was 26%,which included 14%non-right coronary dominance,5%short left main coronary artery(LMCA),and 7%division variations(trifurcation and quadrifurcarion)of the LMCA.The prevalence of CAA was 29%,which included 5%origin anomalies,22%myocardial bridge,and 2%course anomalies.Conclusions:A high prevalence of coronary artery anatomic variations and anomalies in symptomatic patients is reported in this study.Systematic reviews,meta-analyses,reporting guidelines,and unified definitions and classifications of cor-onary variations and anomalies are lacking in the literature,presenting potential opportunities for future research and publications.

A 63-Year-Old Male with D-Transposition of the Great Arteries Who Had an Early Form of the Arterial Switch Operation

We describe a 63-year-old male who appears to have undergone an early form of the arterial switch operation for D-transposition of the great arteries performed in the mid-1960s.We review the clinical and imaging data that support our conclusion.He had a diagnostic cardiac catheterization which demonstrated severe pulmonary hypertension responsive to epoprostenol and oxygen.Our case may represent one example of the experimental surgical work done prior to Dr.Adibe Jatene’s description of thefirst successful arterial switch performed in 1975.

ARTERIAL SWITCH OPERATION FOR COMPLETE D-TRANSPOSITION OF THE GREAT ARTERIES: SURGICAL RESULTS AND ANALYSIS

Objective To review and analyze the surgical results of arterial switch operations in complete D-transposition of the great arteries （TGA）. Methods A total of 113 patients underwent arterial switch operation from Jan. 2001 to Dec. 2005. There were 60 patients with transposition of the great arteries and intact ventricular septum （TGA/IVS） and 53 patients with transposition of the great arteries and ventricular septal defect （TGA/VSD）. The lowest body weight was 2. 3 kg and the smallest age was 6 h. The arterial switch operation was performed under deep hypothermia with circulatory arrest and low-flow perfusion. Results The total mortality was 9. 73%. There were 5 deaths in TGA/IVS （8.3%）, 6 deaths in TGA/VSD （ 11.3% ）. With the development of surgical technique, peri-operative management and cardiopulmonary bypass, the total mortality significantly decreased from 16. 65% in the early times to 5. 5% lately. Conclusion The vital risk of the operation is coronary artery malformation. The incidence of coronary artery malformation is higher in TGA/VSD than in TGA/ [VS. The positional relationship of the great arteries does not affect the results of the operation. The arterial switch operation should be prevented when the pressure ratio between the left and right ventricle is less than 0.6, otherwise it is great likely to cause severe low cardiac output postoperatively.

Capsule endoscopy in celiac disease

Video capsule endoscopy is an attractive and patient- friendly tool that provides high quality images of the small bowel. Obscure gastrointestinal bleeding is the primary and most evaluated indication to capsule endoscopy;however,indications are expanding and a small number of preliminary reports have been presented concerning the role of video capsule endoscopy in the diagnosis of celiac disease. The purpose of this review is to update the current knowledge and to hypothesize on future perspectives of the use of video capsule endoscopy in patients with celiac disease.

Coexistence of acute myocardial infarction with normal coronary arteries and migraine with aura in a female patient

Acute myocardial infarction with normal coronary arteries is a well known condition,which is typically diagnosed in young patients.Coronary vasospasm,inherited,acquired or malignancy-induced hypercoagulable state,collagen vascular disease and coronary arterial embolism have been considered as underlying etiologic factors.An association between migraine with aura and increased risk of ischemic stroke,angina and myocardial infarction has been demonstrated in studies.Patients with migraine and especially with aura should be followed closely against cardiovascular events even if they are young and do not have traditional risk factors.

Does kidney transplantation onto the external iliac artery affect the haemodynamic parameters of the cavernosal arteries？

Reduced cavernosal arterial inflow has been hypothesized to be the likely cause of erectile dysfunction after kidney transplants in recipients revascularized through end-to-end anastomosis to the internal lilac artery, suggesting that end-to-side anastomosis at the external iliac artery is preferable. The aim of this study was to prospectively evaluate the effect of the use of the external iliac artery on erectile function, hormone profiles and penile blood flow by evaluating changes in penile colour Doppler ultrasound parameters in a consecutive series of 22 recipients before and after end-to-side external lilac artery transplantation. The mean International Index of Erectile Function-Erectile Function （IIEF-EF） domain score decreased significantly 3 months after transplant （18.09±6.33 vs. 22.50±7.09, P=O.01）. The reduction in peak systolic velocity （PSV） was significant for the cavernous artery homolateral to the side of transplant （42.60±18.77 vs. 52.01±19.91, P=0.01）. The mean postoperative end diastolic velocity （EDV） did not differ significantly from the preoperative value （P=0.74）. No statistical differences were found in the serum levels of testosterone or prolactin. Kidney grafts anastomosed at the external lilac artery produced significant （P=0.01） reductions in arterial inflow at the homolateral cavernosal artery that remained above the normal threshold. Whether these haemodynamic changes can explain the worsening of postoperative erectile function remains to be proven.

Myocardial infarction with non-obstructive coronary arteries: A comprehensive review and future research directions

Acute coronary syndromes constitute a variety of myocardial injury presentations that include a subset of patients presenting with myocardial infarction with non-obstructive coronary arteries(MINOCA).This acute coronary syndrome differs from type 1 myocardial infarction(MI)regarding patient characteristics,presentation,physiopathology,management,treatment,and prognosis.Two-thirds of MINOCA subjects present ST-segment elevation;MINOCA patients are younger,are more often female and tend to have fewer cardiovascular risk factors.Moreover,MINOCA is a working diagnosis,and defining the aetiologic mechanism is relevant because it affects patient care and prognosis.In the absence of relevant coronary artery disease,myocardial ischaemia might be triggered by an acute event in epicardial coronary arteries,coronary microcirculation,or both.Epicardial causes of MINOCA include coronary plaque disruption,coronary dissection,and coronary spasm.Microvascular MINOCA mechanisms involve microvascular coronary spasm,takotsubo syndrome(TTS),myocarditis,and coronary thromboembolism.Coronary angiography with non-significant coronary stenosis and left ventriculography are first-line tests in the differential study of MINOCA patients.The diagnostic arsenal includes invasive and non-invasive techniques.Medical history and echocardiography can help indicate vasospasm or thrombosis,if one finite coronary territory is affected,or specify TTS if apical ballooning is present.Intravascular ultrasound,optical coherence tomography,and provocative testing are encouraged.Cardiac magnetic resonance is a cornerstone in myocarditis diagnosis.MINOCA is not a benign diagnosis,and its polymorphic forms differ in prognosis.MINOCA care varies across centres,and future multi-centre clinical trials with standardized criteria may have a positive impact on defining optimal cardiovascular care for MINOCA patients.

Successful endovascular treatment in patients with acute thromboembolic ischemia of the lower limb including the crural arteries

AIM To examine the efficacy and safety of the 6 French(6F) Rotarex~S catheter system in patients with acute limb ischemia(ALI) involving thromboembolic occlusion of the proximal and mid-crural vessels.METHODS The files of patients in our department with ALI between 2015 and 2017 were examined. In seven patients, the Rotarex~S catheter was used in the proximal segment of the crural arteries. Data related to the clinical examination, Doppler sonography, angiography and followup from these patients were further used for analysis.RESULTS Two patients(29%) had thrombotic occlusion of the common femoral artery, and the remaining five exhibited thrombosis of the superficial femoral artery and popliteal artery. Mechanical thrombectomy was performed in all cases using a 6F Rotarex~S catheter. Additional Rotarex~S catheter thrombectomy due to remaining thrombus formation with no reflow was performed in the anterior tibial artery in two of seven cases(29%), in the tibiofibular tract and posterior tibial artery in two of seven cases(29%) and in the tibiofibular tract and fibular artery in the remaining three of seven cases(43%). Ischemic symptoms resolved promptly in all, and none of the patients experienced a procedural complication, such as crural vessel dissection, perforation or thrombus embolization.CONCLUSION Mechanical debulking using the 6F Rotarex~S catheter system may be a safe and effective treatment option in case of thrombotic or thromboembolic occlusion of the proximal and mid-portion of crural arteries.

Refractory celiac disease and sprue-like intestinal disease

Celiac disease is a gluten-dependent small intestinal mucosal disorder that causes malabsorption, often with diarrhea and weight loss. Diagnosis is based on detection of typical biopsy changes in the proximal small bowel, followed by evidence for an unequivocal response to a gluten-free diet. Refractoriness in celiac disease may be due to poor diet compliance, sometimes intentional, or consumption of ubiquitious sources of gluten. Alternatively, the original diagnosis may not be correct (eg., duodenal Crohn's disease), or a second cause for symptoms may be present (eg., collagenous colitis, functional bowel disorder). In some with recurrent symptoms, a complication may be present (eg., collagenous sprue, small bowel carcinoma, lymphoma). In some, a response to a gluten-free diet can not be unequivocally defined, and more precise historical terms have been used including "sprue-like intestinal disease" or "unclassified sprue". Although a "wastebasket diagnosis", these likely represent a heterogeneous group, and some, but not all, may develop lymphoma. Precise definition will be critical in the future as an array of new treatments, including biological agents, may emerge.