This approach would be particularly beneficial in obese patients. Such miniature endoscopic systems are not yet available commercially, but are currently in development. Another problem that is inherent to any HIFU system with ultrasound guidance is the absence of direct operator control over the thermal dose that the target tissue received. In order to estimate thermal dose, one needs to know the output acoustic energy of the device, the absorption coefficient of the target tissue Inhibitors,research,lifescience,medical and the attenuation by the intervening tissue (primarily abdominal wall and viscera). Therefore, careful calibration of HIFU fields and studies on in-vivo measurement of acoustic attenuation and absorption in different tissues are of great importance

(46). Summary HIFU ablation has been shown a promising method for palliative treatment of pancreatic tumors.

A number of preliminary studies suggest that this technique is safe and can be used alone or in combination with systemic chemotherapy Inhibitors,research,lifescience,medical or radiation therapy. Further clinical trials are currently being planned and will help to define the future role of HIFU in the treatment of patients with pancreas cancer. Footnotes No potential conflict of interest.
Pancreatic Baricitinib ic50 cancer presents as a locally advanced Inhibitors,research,lifescience,medical or metastatic cancer in most patients and only about 20-25% of patients present with a potentially resectable cancer. Even in these patients, the 5-year survival rate after a successful pancreaticoduodenectomy (PD) or pancreatectomy is approximately 15-20% (1). Patients who undergo a margin positive Inhibitors,research,lifescience,medical resection (R2 or R1) do poorly and their survival is similar to those with locally advanced disease (2)-(5). Given the systemic nature of pancreatic adenocarcinoma, and the morbidity involved with surgery, it is essential to clearly determine the resectability status at the time

of initial staging evaluation. This is best accomplished by a computerized tomography (CT) scan optimized for pancreatic imaging (6). Based on this high quality CT imaging, pancreatic tumors are classified as resectable, locally advanced or metastatic. Tumors of “borderline resectability” are emerging as of a distinct Inhibitors,research,lifescience,medical subset of pancreatic tumors and do not easily fit the traditional categories of resectable or locally advanced pancreatic cancers (7),(8). It is important to make this distinction because these presentations tend to confound the results of clinical trials and misguide treating physicians – i.e. in the absence of objective criteria for preoperative staging, some patients with borderline resectable pancreatic cancer will be treated as if they have resectable cancer (with an increased risk of margin positive resection) while others will be treated as having locally advanced disease (and suggest ‘dramatic’ downstaging and operability). These patients are poor candidates for upfront PD given the high rate of margin positive resection and in selected patients; preoperative therapy can achieve an R0 resection surgery.

Two randomized controlled trials of the GF/CF diet indicated that it may improve symptoms in some children,37,38 although these trials were small, both in terms of size and duration. Although the GF/CF diet may improve symptoms by inducing changes in the microbiota and/or their metabolites, another mechanism #GF109203X randurls[1|1|,|CHEM1|]# is by increasing gut integrity. Abnormally high intestinal Inhibitors,research,lifescience,medical permeability (IPT), or a “leaky gut,”

has also been associated with autism, suggesting that autistic individuals may have increased sensitivity to components of our diet and their metabolites, because they Inhibitors,research,lifescience,medical can more easily access the bloodstream.56 Autistic individuals on a GF/CF diet had significantly lower intestinal permeability compared with individuals on an unrestricted diet.56 Genetic factors have also been implicated in impaired gut integrity in autistic individuals; a mutation affecting the expression of the gene encoding the MET receptor tyrosine kinase has been associated with both ASD and gastrointestinal conditions, and functions Inhibitors,research,lifescience,medical in both brain development and gastrointestinal repair.57 To our knowledge no study has evaluated how the Inhibitors,research,lifescience,medical GF/CF diet affects the structure, gene expression,

and function of the gut (fecal) microbiota or microbiome. In general, studies of the gut microbiota in children with ASDs have been very limited, typically examining just a few

subjects, with shallow sequencing of bacterial 16S rRNA gene amplicons generated from just a few biospecimens/participant (ie, extensive time series studies have not been performed), and without concomitant analyses Inhibitors,research,lifescience,medical of (i) microbiome gene content (by shotgun sequencing of total fecal community DNA); (ii) microbiome gene expression (by RNA-Seq profiling Olopatadine of the community’s meta-transcriptome); or (iii) microbial metabolism (or host-microbial cometabolism, eg, by MS or NMR). Several groups are currently conducting these types of analyses. The results may identify microbiota/microbiome biomarkers useful for improved classification schemes, for understanding pathophysiology, and for monitoring the efficacy of therapeutic interventions. With improved phenotyping (eg, using functional magnetic resonance imaging [fMRI] or monitoring eyetracking) earlier diagnosis may be possible, allowing for prospective characterizations of microbial community metabolism and host-microbial cometabolism during postnatal development (and in the mother).

​(Fig.2,2, Table S1; all slices displayed in Fig. S2). No regions showed greater ICD in meditators compared

to novices. Figure 2 Brain regions showing less intrinsic connectivity 5-HT receptor agonist and antagonist drugs during loving kindness meditation in meditators as compared to novices (P < 0.05 FWE, cluster corrected; slices displayed left to right). Seed-based functional Inhibitors,research,lifescience,medical connectivity Whole-brain contrast maps revealed a significant difference in functional connectivity with the PCC/PCu during loving kindness meditation between meditators and novices. Novices showed greater functional connectivity between the PCC/PCu and clusters in the bilateral Inhibitors,research,lifescience,medical parahippocampal gyrus, hippocampus, cerebellum, precuneus, posterior cingulate cortex, and posterior insula lobe; and the bilateral middle orbital gyrus, anterior

cingulate cortex, and superior medial gyrus (Fig. ​(Fig.3,3, Table S2; all slices displayed in Fig. S3). Meditators showed greater Inhibitors,research,lifescience,medical functional connectivity between the PCC/PCu and clusters in the left IFG, middle frontal gyrus and insula lobe, and the right cerebellum (Fig. ​(Fig.4,4, Table S3; all slices displayed in Fig. S4). Figure 3 Brain regions showing greater Inhibitors,research,lifescience,medical functional connectivity with the posterior cingulate cortex/precuneus during loving kindness meditation in novices than meditators

(P < 0.05 FWE, cluster corrected; slices displayed left to right). Figure 4 Brain regions showing greater functional connectivity with the posterior cingulate cortex/precuneus during loving kindness meditation in meditators than novices (P < 0.05 FWE, cluster corrected; slices displayed Inhibitors,research,lifescience,medical left to right). Discussion This fMRI study describes the neural substrate of loving kindness meditation in meditators as compared to novices. To our knowledge, no prior neuroimaging study has reported see more on the neural substrate of loving kindness without a concurrent task. In addition to GLM analyses, we used a relatively novel method, the ICD, to identify regions of the brain that differ in the degree of connectivity between groups during loving kindness meditation. On the basis of our prior interest in the PCC/PCu, we used secondary seed-based analysis to identify which connections with this brain region differed between groups during loving kindness meditation. Overall, meditators showed reduced BOLD signal and intrinsic connectivity during loving kindness meditation as compared to novices.

A further complicating issue in the differential diagnosis between PTSD and TBI is the range of other comorbid problems that commonly coexist with both TBI and PTSD. For example, depression is highly prevalent with both conditions. Numerous studies have suggested that TBI increases the risk for developing depression,29,30 eg, refs 31,32,33. Some of the core symptoms noted across TBI and PTSD are also seen in depression, especially the more severe forms of TBI, including concentration problems, memory problems, irritability, reduced motivation,

and fatigue. Highlighting this problem in one study was a finding that more than 50% of depressed Inhibitors,research,lifescience,medical patients met symptom criteria for moderate/severe postconcussive Inhibitors,research,lifescience,medical syndrome.34 This contributes to the conclusion that some of the symptoms attributed to TBI may in fact be generic symptoms of psychological malaise, which are observed across anxiety and depressive responses. Complicating the issue of comorbidity is

compounded by the fact that TBI, PTSD, and depression commonly occur in the context of chronic pain, which Inhibitors,research,lifescience,medical also results in symptoms that overlap with each of these conditions.35-41 Prevalence PTSD and TBI are not uncommon. Epidemiological studies indicate that most people in the community have been exposed to traumatic stressors,42,43 although anly a minority develop PTSD. For example, the National Comorbidity Survey found that 21 % of the women and 8% of the men had developed PTSD.42 Similarly, a Detroit study found that 13% of the women and 6% of the men had developed PTSD.43 That is, although men are more likely to be exposed to trauma than women, women have at least a twofold risk of developing PTSD compared with men. 44 More severe Inhibitors,research,lifescience,medical traumas tend to result in more severe PTSD. Interpersonal violence Inhibitors,research,lifescience,medical leads to

more PTSD than impersonal trauma; for example, whereas 55% of rape victims develop PTSD, only 7.5% of accident victims develop PTSD:42,45 In terms of TBI, there are between 1.5 and 2 million people in the USA alone who sustain a TBI, with approximately 70 000 to 90 000 experiencing persistent functional difficulties.46 The Centers for Disease Control and Prevention Selleck Galunisertib estimates that approximately 5.3 million people in the USA are living with a disability due to TBI.47 of Certain populations appear to be more at risk of sustaining TBIs. For example, military estimates of mild TBI of deployed (non-mcdically evacuated) personnel indicate that between 10% and 20% may have suffered a mild TBI during deployment.48 One study reported a rate as high as 23% in personnel assessed after returning to the USA.49 Can PTSD develop following TBI? Some earlier commentators argued that PTSD could not develop following TBI because the impaired consciousness at the time of trauma precluded encoding of the traumatic experience, and this prevented trauma memories that are necessary for PTSD development.50,51 In contrast, evidence has accumulated that PTSD can develop following mild TBI.

Minor intellectual deficits are present in many patients in contrast with CDM and childhood onset DM1. Avoidant, obsessive-compulsive and passive-aggressive personality features have also been

reported (24, 25). Nocturnal apnoeic episodes and daytime sleepiness are a common manifestation. Gastrointestinal tract involvement covers irritable bowel syndrome, symptomatic gall stones and gamma-glutamyltransferase elevations. Finally, endocrine abnormalities include testicular atrophy, hypotestosteronism, insulin resistance with usually mild type-2 diabetes, thyroid dysfunction. Late-onset/asymptomatic DM1 In late-onset or asymptomatic Inhibitors,research,lifescience,medical patients (with low number of CTG repeats), only limited features are found on clinical and paraclinical assessment. Myotonia, weakness and excessive daytime sleepiness are rarely present. Before DNA tests became Inhibitors,research,lifescience,medical available, there were many examples of incorrect ascertainment, even when using markers such as EMG evidence of myotonia and slitlamp examination for the characteristic cataracts (26). In late-onset patients, the search for cataracts is helpful for identifying the transmitting person. Myotonic Dystrophy type 2 Clinical features The prevalence of DM2 is not well established, but estimated

to be similar to DM1 in European populations (27). In DM2 there Inhibitors,research,lifescience,medical are no distinct clinical subgroups although initially different phenotypes of DM2 were described: DM2/PROMM and PDM (5-7). The most important discrepancy between DM1 and DM2 is absence of a congenital or early-onset form in DM2 (12, 28) and the clinical presentation is a more continuum from early adult-onset Inhibitors,research,lifescience,medical severe form to very late–onset mild Inhibitors,research,lifescience,medical symptoms (paucisymptomatic). Clinically based ascertainment of DM2 patients is even more difficult because of the large phenotypic variability and a large number of individuals with www.selleckchem.com/products/Acadesine.html milder symptoms who remain undiagnosed. Moreover, milder phenotypes with

prominent myalgia may easily be misdiagnosed as fibromyalgia (29) and patients with onset of slowly progressive proximal muscle weakness after age 70 years may not be referred Rebamipide for neuromuscular investigations. Further evidence that a large proportion of DM2 patients may be undiagnosed came from a recent study which indicate that co-segregation of heterozygous recessive CLCN1 mutations in DM2 patients is higher than expected (30). In DM2 patients with co-segregating CLCN1 the severity of myotonia appear to be more evident either clinically or on EMG, thus these patients could be more easily identified and diagnosed than DM2 patients without the modifier allele. Consequently the majority of DM2 patients remains undiagnosed even in clinical centers with considerable experience with DM2.

An attempt was also made to constrain our kinetic parameters by training them with data based on three distinct experimental conditions. However, our model was able to predict only one state revealing the limits of using FBA steady states to constrain a dynamic model. Optimisation techniques can be used to estimate kinetic parameters based on

simulated or experimental data [34,35]. However, these estimated parameter values are usually not unique given a set of an input data due to mathematical redundancy Inhibitors,research,lifescience,medical [29]. This redundancy means that multiple sets of parameter values can fit to an experimental data series equally well. There have been attempts in the past to reduce redundancy in parameter estimation. One noticeable approach is the use of Dynamic Flux Estimation (DFE) proposed by Goel et al [25] where there is a verification of mass conservation within metabolic time-series data and fluxes are expressed as functions of the relative variables affecting them. Although results from DFE show Inhibitors,research,lifescience,medical that redundancy can be reduced, the approach Inhibitors,research,lifescience,medical is computationally expensive due to the internal verification process. 4. Conclusions In this article, we developed a genome-scale kinetic

model of Mycobacterium tuberculosis based on generic kinetic equations. The model has 739 metabolites, 856 metabolic reactions and 856 enzymes. All kinetic parameters were Inhibitors,research,lifescience,medical estimated using a genetic algorithm based on the stoichiometry of reactions and flux distributions in the network. Our results show a near-perfect agreement with flux distributions under different growth conditions.

The kinetic parameters used in our model were estimated using only fluxes, therefore there remains a degree of redundancy in parameter values. To further improve Inhibitors,research,lifescience,medical the selleck inhibitor predictive power of genome-scale dynamic models, the integration of more experimental data types including gene expression, proteomics and metabolomics, as well as the use of dynamic training data sets, will be needed. Nevertheless, our method for constructing a genome-scale kinetic model of M. tuberculosis represents a platform for further model development and analysis. Acknowledgments D.A.A. is supported by a studentship from the Biotechnology and Biological Sciences Research Council (BBSRC), UK. Supplementary Files Supplementary File 1 Supplementary (ZIP, 69 KB) Click here for additional data file.(69K, zip) Adenylyl cyclase Supplementary File 2 Supplementary (ZIP, 74 KB) Click here for additional data file.(74K, zip) Supplementary File 3 Supplementary (ZIP, 79 KB) Click here for additional data file.(79K, zip) Supplementary File 4 Supplementary (XLSX, 103 KB) Click here for additional data file.(103K, xlsx) Supplementary File 5 Supplementary (DOCX, 23 KB) Click here for additional data file.(23K, docx) Supplementary files Supplementary files Supplementary File 1: Model of M.

Focusing on what is known

as “the prodromal period” will also make it possible to characterize a subset of individuals who are at risk and go on to develop schizophrenia, versus another subset of individuals who are at risk but who do not go on to develop schizophrenia. A focus on this group of subjects will also make it possible to learn more about the timing of brain abnormalities in schizophrenia, and to begin to develop putative brain markers or brain signatures that predispose an individual to develop schizophrenia. Another approach is to study family members of schizophrenic Inhibitors,research,lifescience,medical patients in order to discern brain abnormalities that are associated with genetically regulated Inhibitors,research,lifescience,medical variations in brain structure, but which are neither necessary nor sufficient for the SB590885 cell line development of psychosis. Some of these strategies, along with recent findings, are reviewed, below. High-risk studies To address the question of “what is the timing of brain abnormalities in schizophrenia?” it is useful to study individuals who are at high risk for developing schizophrenia, but who have not yet developed the disorder, ie, before psychosis begins. As noted above, this can be addressed to some extent with longitudinal studies, but can also be addressed Inhibitors,research,lifescience,medical by studying individuals who are at high risk for developing

schizophrenia, as one can observe whether or not there are brain abnormalities present prior to Inhibitors,research,lifescience,medical onset of schizophrenia. This approach is quite appealing

given that there is evidence to suggest that as many as 35% of individuals defined as being at ultra high-risk for schizophrenia convert to schizophrenia within the first year of being indentified17 (see also discussion below). With respect to high-risk studies, two of the largest and best known research programs come to mind. The first Inhibitors,research,lifescience,medical is the Edinburgh High-Risk Study (EHRS),47 which evaluates individuals at risk for developing schizophrenia. The EHRS defines “at-risk” based on cognitive impairment measures from the Structural Interview for Schizotypy (SIS). Findings thus far indicate that indi viduals who are at risk and who also have schizotypal no features tend to have increased right prefrontal cortical folding, which further predicts those individuals who develop schizophrenia. These investigators speculate that abnormalities in cortical folding reflect disordered connectivity in the right prefrontal lobe. The second large research program to evaluate individuals at risk for psychosis is the Melbourne Ultra HighRisk Studies, in collaboration with the Personal Assessment and Crisis Evaluation (PACE) clinic. This study investigates individuals at risk for developing psychosis.

2004). In Thailand, almost all (94%) ECT administration was unmodified (Chanpattana and Kramer 2004). In India, both modified and unmodified ECT was administered (Chanpattana et al. 2005b), 52% of patients received unmodified at 50% of all institutions, and 30% of institutions administered only unmodified. BI-6727 Overall in Asia, only 45% of facilities used modified ECT exclusively (Chanpattana et al. 2010), in Hong Kong 87% modified (Chung et al. 2003), and the Asian Pacific Region (Little Inhibitors,research,lifescience,medical 2003) and Katmandu, Nepal, used only modified (Ahikari et al. 2008). Eight facilities in Asia reported succinylcholine muscle relaxant used routinely without anesthesia (Chanpattana et al.

2010). Anesthesia was also used without muscle relaxants in Japan, and extreme motion from the convulsions held down with aid of assistants restraining Inhibitors,research,lifescience,medical patient’s shoulders, arms, and thighs (Ishimoto

et al. 2000). Overall, 26% Latin American countries used unmodified ECT (Levav and Gonzalez 1996), except for all modified in Rio de Janeiro, Brazil and one country in the Caribbean (Levav and Gonzalez 1996; Pastore et al. 2008). Placement and devices On a worldwide scale, Inhibitors,research,lifescience,medical BL placement was the preferred electrode placement. However, UL placement was the first main choice in Australia and New Zealand (O’Dea et al. 1991; Ministry of Health 2005; Chanpattana 2007; Lamont et al. 2011), likewise to several European countries such as Vienna (Tauscher et al. 1997), Munich Inhibitors,research,lifescience,medical (Baghai et al. 2005), Netherlands (van Waarde et al. 2009), and Norway (Schweder et al. 2011b). In the United States, there was some sine wave (2%) (Prudic et al. 2001) and some UL (16–21%) (Reid et al. 1998; Scarano et al. 2000; Prudic et al. 2001) report, but BL placement (73–79%) and brief-pulse wave current (Reid et al. 1998; Scarano et al. 2000; Prudic et al. 2001) was mainstream. Similarly, brief-pulse wave current devices were dominant Inhibitors,research,lifescience,medical in Europe, except sine-wave current still used in Spain 14% (Bertolin-Guillen et al. 2006), Russia 26% (Nelson 2005),

Belgium 34% (Sienaert et al. 2006), Poland 30% (Gazdag et al. 2009a), Germany 39% (Muller et al. 1998), and Hungary 52% (Gazdag et al. 2004a). Overall electrode placement in Asia was BL (77%) (Chanpattana et al. Resminostat 2010). Thailand (Chanpattana and Kramer 2004) and Japan (Motohashi et al. 2004) reported only the use of BL and India always reported the use of BL in 82% (Chanpattana et al. 2005b). In Asia, 58% of institutions used brief-pulse devices and 42% sine wave (Chanpattana et al. 2010). In Japan, the device type was often Japanese-produced Sakai C1, but also some had Thymatron® DGx devices (Somatics, Inc., http://www.thymatron.com) (Chanpattana et al. 2005a). In India, a diversity of devices was in use, including locally made (Chanpattana et al. 2005b). In Katmandu, Nepal, device type was only brief pulse (Ahikari et al. 2008).

14,15 From a legal

perspective, each country or state has its legal regulations for death. On the basis of these regulations, each hospital establishes criteria for the determination of brain death. Subsequently, a large variability in the determination of brain death between and within individual hospitals has been see more reported in American and European hospitals.14,15 ETHICAL RULES FOR LIVING DONORS Living Inhibitors,research,lifescience,medical donor donations are widely used worldwide, and the numbers are constantly increasing. According to recent publications, 27,000 living donor kidney and 2,000 living donor liver transplants are performed worldwide annually.16,17 The shortage of deceased donor organs led to a steady increase in live donors over the last years. The ethical rules for live donation are different than those for deceased donors, but what is common to both is the Inhibitors,research,lifescience,medical extensive

attention to the act of organ donation by ethicists, religions, and the medical communities. The majority of live organ donations are kidney Inhibitors,research,lifescience,medical transplants, followed by partial liver and partial lung transplants. The main ethical principle in live donations is to cause little or no harm to the donor. Organ donations between family members are well accepted and valued by society. It is also accepted that altruistic donations, those with a pure and non-financial motivation to help a patient suffering, are a noble thing. However, any donation which is associated with financial payment for Inhibitors,research,lifescience,medical the organ is generally unacceptable. While arguments are voiced that patients may have the rights over their bodies and they can “sell” organs as they wish, it is widely accepted that such practice is unethical and should be banned. Organ trafficking has been and continues to be a major problem in the world. Modern societies worldwide are now strictly against organ trafficking, and international

actions are taken to prevent such cases. In 2008, the Declaration of Inhibitors,research,lifescience,medical Istanbul on Organ Trafficking and Transplant Tourism, the European Parliament, and the Asian Sclareol Taskforce on Organ Trafficking each issued formal statements urging member states to define conditions in which reimbursement can be granted.18 A clear distinction is made between the acceptable practice of reimbursement of legitimate expenses incurred due to the transplant process and payment resulting in illegal financial gain. In Israel, according to a recent law on organ transplantation that is in effect since 2008, direct payments to donors from another source or from insurance are now illegal.19 At the same time the law allows for compensation of the direct expenses of organ donation incurred by the donor and also adjustment of his medical insurance benefit to his new more liable condition.

The patient had attained menopause 3 months earlier, before which she had regular cycles. There was no history of cough with expectoration, headache, arthralgia, and rash, and nor was there a history of recent travel to malaria endemic zone or exposure to any patient of tuberculosis. Examination of the patient revealed pulse rate of 118 per minute, blood pressure of 110/70 mm Hg (supine), and oral temperature of 38.3°C (101°F). She had moderate conjunctival pallor and scleral icterus. There was no lymphadenopathy, clubbing, eschar, or skin rashes. Oxygen saturation was 99% on room air, and there were no signs of respiratory Inhibitors,research,lifescience,medical distress in

the patient. Cardiovascular examination revealed a systolic flow murmur in the aortic area. The respiratory and nervous system examinations

were within normal limits. Her chest X-ray and abdomen ultrasound revealed no significant Inhibitors,research,lifescience,medical abnormalities except for mild hepatomegaly. Routine hematological evaluation, on admission, revealed very low hemoglobin (Hb); 22 g/L (120-160), hematocrit; 7.2% (35-45), total leukocyte count (TLC); 3×109/L (4-11), total platelet count (TPC); 64.5×109/L (150-450), absolute neutrophil count; 1.9×109/L (1.5-8×109/L), corrected Belinostat mouse reticulocyte count; 1.5% (0.5-2), Inhibitors,research,lifescience,medical red cell distribution width; 17.5% (11.5-14.5), mean corpuscular volume (MCV); 114.3 fL (80-98), mean corpuscular hemoglobin (MCH); 34.9 pg (26-32), and mean corpuscular hemoglobin Inhibitors,research,lifescience,medical concentration (MCHC); 30.6% (32-36). Peripheral smear showed pancytopenia

with a moderate degree of anisopoikilocytosis and a good number of macrocytes, macro-ovalocytes, and hypersegmented neutrophils. Bone marrow aspiration and trephine biopsy from the right posterior superior iliac Inhibitors,research,lifescience,medical spine revealed marked hypercellularity for age (70%), florid erythroid hyperplasia with an altered myeloid to erythroid ratio (1:2), megaloblastic dyspoiesis, and numerous giant metamyelocytes. Micromegakaryocytes and/or megakaryocyte clustering were not seen. Perl stain showed PAK6 adequate marrow iron stores without any ring sideroblasts. There was no evidence of blast prominence (4%), granulomas, hemoparasites, malignancy, or increased reticulin condensation (figures 1 and ​and2).2). The bone marrow morphology was suggestive of megaloblastic anemia, which was confirmed biochemically by low levels of serum vitamin B12 (59.6 pg/mL, reference; 180- 900), low normal folic acid (3.9 ng/mL, reference; 4-24), and markedly elevated serum lactate dehydrogenase (LDH) [10,550 IU/L, reference; 225-420]. The patient’s routine liver and renal function tests were within normal limits except for mild unconjugated hyperbilirubinemia (total bilirubin; 4.8 mg/dL [0.2-1.2]/direct; 0.4 mg/dL [up to 0.3]). Her upper and lower gastrointestinal endoscopy did not show any abnormality.