22 First, we excluded patients age <30 and >100 years old. To enroll patients with type 2 diabetes, click here we further excluded those who (1) had a hospital admission

with a discharge diagnosis of insulin dependent diabetes mellitus (ICD-9-CM code 250.x1, 250.x3), or (2) received a catastrophic illness certificate issued by the Department of Health for type 1 diabetes (Fig. 1). Patients were classified as having prevalent or newly diagnosed type 2 diabetes according to the criteria in 1999. Those who had a history of cancer recorded in the National Cancer Registry any time before the cohort entry date, that is, date of diabetes diagnosis for newly diagnosed patients and January 1 2000 for prevalent patients, were also excluded. Patients were followed from January 1 2000 (for prevalent type 2 diabetes patients) or the date of diabetes diagnosis in 2000 (for newly diagnosed type 2 diabetes patients) to the earliest of cancer diagnosis, death, disenrollment from the national health insurance, selleck or December 31 2007. All individuals in the study cohort with the first occurrence of liver, colorectal, lung, and urinary bladder cancer were included as cases. All potential cases were validated by a linkage

through National Cancer Registry. A risk-set sampling (that is, controls sampled from those in the original study cohort who remained free of outcome at the time point when a case occurred) matched by age (within 5 years), sex, and the number of days of follow-up was used to find controls for the

cohort. For newly diagnosed type 2 diabetes patients, cases and controls were also matched on antidiabetic treatment duration (within 30 days) at cancer diagnosis. For newly diagnosed diabetic patients, this scheme that matched follow-up duration would have, by design, also taken diabetes duration into consideration. For prevalent patients with unknown duration, we selected controls with the same follow-up duration to reduce the confounding effect by diabetes duration. Up to four controls were selected for each case. The main exposure of interest was the use of rosiglitazone and pioglitazone, which entered Taiwan’s market in March 2000 and selleck compound June 2001, respectively. We collected information of prescribed drug types (according to the anatomic therapeutic chemical [ATC] classification system, A10BG02 for rosiglitazone and A10BG03 for pioglitazone), dosage, date of prescription, supply days, and total number of pills dispensed from the outpatient pharmacy prescription database. The mean daily dose for each individual was calculated as dividing the cumulative number of pills by the follow-up duration. Subsequently, the defined daily dose (DDD) was then established by an expert panel according to the relative amount compared to the typical maintenance dose for an adult.

The term also gives no clue as to whether the problem is primarily a motor or sensory one. Typically, patients complain of the feeling of food/drink sticking, or a discomfort either in the throat or retrosternally, or simply being able to “sense” the act of swallowing; occasionally, regurgitation, aspiration, or even hiccup may be the presenting complaint.2

The most important first step in assessing dysphagia is to determine whether it is oropharyngeal or esophageal in origin, as their potential causes and subsequent investigation and management can differ greatly. This can Pexidartinib supplier usually be achieved through taking a careful history, which has been shown to accurately differentiate between oropharyngeal, esophageal, and neuromuscular causes of dysphagia in up to 85% of patients.3 It is important to know if the dysphagia is present only during swallowing or at all times, the latter suggests potential sensory dysfunction, and the most common disorder is globus hystericus. Dysphagia that occurs only during swallowing of solids is more likely to indicate underlying mechanical obstruction, whereas when both solids and liquids are affected, dysmotility is the likely cause. The presence of symptoms such as delayed or absent swallow initiation, Selumetinib order cough post-swallowing, nasopharyngeal

regurgitation, and repeated swallows to effect pharyngeal clearance, indicate potential oropharyngeal dysphagia.2 Localization of the hold-up site based on symptom is not always a reliable guide to the site of the obstruction.2,4 However, dysphagia felt in the throat is more likely to be oropharyngeal in origin as compared with that in the retrosternal region, which is more suggestive of an esophageal disorder. The duration and progression of symptoms are also important features. Chronic and stable symptoms suggest benign conditions such as peptic strictures or Schatzki’s ring, while rapidly progressive symptoms, especially in association with weight loss, indicate a more sinister cause. The presence of regurgitation immediately after swallowing suggests esophageal retention of food, whereas regurgitation in between meals indicates the presence

of a pharyngeal pouch or Zenker’s diverticulum. Dysphagia that occurs after a long history of reflux symptoms, especially with patients giving a history of poor symptom control, may suggest the development click here of complications such as peptic stricture, Barrett’s esophagus and possibly, esophageal adenocarcinoma. Patients with known esophageal dysmotility often have volume reflux, and throat irritation caused by reflux can induce the sensation of dysphagia. In young patients who present with dysphagia or food bolus obstruction, especially those with a history of atopy, eosinophilic esophagitis must be suspected and esophageal biopsies must be performed on subsequent gastroscopy. Dysphagia may be a complication of systemic disease or medication.

The term also gives no clue as to whether the problem is primarily a motor or sensory one. Typically, patients complain of the feeling of food/drink sticking, or a discomfort either in the throat or retrosternally, or simply being able to “sense” the act of swallowing; occasionally, regurgitation, aspiration, or even hiccup may be the presenting complaint.2

The most important first step in assessing dysphagia is to determine whether it is oropharyngeal or esophageal in origin, as their potential causes and subsequent investigation and management can differ greatly. This can PI3K Inhibitor Library datasheet usually be achieved through taking a careful history, which has been shown to accurately differentiate between oropharyngeal, esophageal, and neuromuscular causes of dysphagia in up to 85% of patients.3 It is important to know if the dysphagia is present only during swallowing or at all times, the latter suggests potential sensory dysfunction, and the most common disorder is globus hystericus. Dysphagia that occurs only during swallowing of solids is more likely to indicate underlying mechanical obstruction, whereas when both solids and liquids are affected, dysmotility is the likely cause. The presence of symptoms such as delayed or absent swallow initiation, Tyrosine Kinase Inhibitor Library cough post-swallowing, nasopharyngeal

regurgitation, and repeated swallows to effect pharyngeal clearance, indicate potential oropharyngeal dysphagia.2 Localization of the hold-up site based on symptom is not always a reliable guide to the site of the obstruction.2,4 However, dysphagia felt in the throat is more likely to be oropharyngeal in origin as compared with that in the retrosternal region, which is more suggestive of an esophageal disorder. The duration and progression of symptoms are also important features. Chronic and stable symptoms suggest benign conditions such as peptic strictures or Schatzki’s ring, while rapidly progressive symptoms, especially in association with weight loss, indicate a more sinister cause. The presence of regurgitation immediately after swallowing suggests esophageal retention of food, whereas regurgitation in between meals indicates the presence

of a pharyngeal pouch or Zenker’s diverticulum. Dysphagia that occurs after a long history of reflux symptoms, especially with patients giving a history of poor symptom control, may suggest the development selleckchem of complications such as peptic stricture, Barrett’s esophagus and possibly, esophageal adenocarcinoma. Patients with known esophageal dysmotility often have volume reflux, and throat irritation caused by reflux can induce the sensation of dysphagia. In young patients who present with dysphagia or food bolus obstruction, especially those with a history of atopy, eosinophilic esophagitis must be suspected and esophageal biopsies must be performed on subsequent gastroscopy. Dysphagia may be a complication of systemic disease or medication.

We hypothesized that the call is specific to provisioning behavior in the context of parent–offspring communication, and tentatively designated it ‘provisioning call’. To test this hypothesis, we observed nesting females in the laboratory to determine if and when they emitted the call, and the response of nymphs. In every case, the call was clearly coordinated with female provisioning behaviors: females emitted the call only upon returning to their nests with a drupe. Moreover,

nymphs quickly gathered to the drupe while the female was calling. Because nymphs usually hide in crevices throughout the nest debris while the mother is foraging, we also hypothesized that the provisioning call functions to induce nymphs to gather and feed synchronously on newly provisioned drupes. A playback experiment indicated that significantly more nymphs gathered on a drupe with the playback call than without the http://www.selleckchem.com/products/ldk378.html call,

supporting this hypothesis. Furthermore, observations through nymphal development revealed that the total length of all sound bouts in a single provisioning this website call was shorter for females with older nymphs. This is consistent with the assumption that older nymphs should gather on the provisioned drupe more quickly than young, less-motile nymphs. To the best of our knowledge, this is the first report of a parent producing sound and/or vibration signals directly to offspring at repeated progressive provisioning events in a subsocial insect. “
“Apex predators are essential for the viability of healthy ecosystems. By studying carnivoran feeding ecology, we can obtain a better understanding of the ecological limits, resilience and predator–prey dynamics that govern these populations. However, monitoring elusive predators – like the leopard Panthera pardus – is often fraught with logistical and financial constraints, particularly selleckchem in inaccessible terrain. In this study, we identified clusters of Global Positioning System (GPS) points

from four GPS-collared leopards and investigated them in the field for potential kills. Environmental data from cluster sites were gathered alongside spatial and temporal data collected via GPS cluster analysis to develop statistical models capable of predicting the occurrence of leopard predatory events. Our results demonstrate that leopard predation can be accurately modelled either by using a combination of field data (i.e. collected at cluster sites) and remote data (i.e. obtained via GPS analysis), or simply remote data alone. Kills were more likely to be present at clusters where leopards exhibited longer handling times, at sites with dense vegetation cover, when leopards were more active 12 h before the cluster than 12 h after, where more tree refugia were present, in areas of higher elevation, at sites containing low levels of shrub cover, and when clusters began during diurnal or crepuscular hours.

Lactobacillus johnsonii MH-68 and L. salivarius subsp. salicinius AP-32 effectively suppress H. pylori viability, and when used as probiotics, they may help decrease the occurrence of gastritis, and even reduce the risk of H. pylori

infection. “
“Background:  viral and bacterial antigens have been suspected to be able to mimic the antigenic profile Ensartinib research buy of the thyroid cell membrane and to play an important role in the onset of the autoimmune diseases, such as Graves’ disease and Hashimoto thyroiditis. The Helicobacter pylori infection is worldwide diffused and is present in the developed countries up to 50% of the population. The presence of the cytotoxin-associated gene A antigens identifies the most virulent strains of the bacterium. Previous studies have demonstrated the possible correlation between the Helicobacter pylori and Hashimoto’s thyroiditis but these results are controversial. Aims:  We studied the prevalence rate of this bacterium in the Graves’ disease and two selected subgroups such as the hyperthyroid patients, at the first time of diagnosis, and the euthyroid methimazole-treated patients. Materials and Methods:  We analyzed Helicobacter pylori in fresh stool samples with an enzyme immunoassay method and the presence of cytotoxin-associated gene A antigens with a serological test. Results:  Our results show that a significative increased rate of prevalence is present in Graves’ patients, when the disease is ongoing,

with an overall prevalence of the strains expressing the cytotoxin-associated gene A antigens compared to the control group. Conclusions:  The association between the find more Helicobacter pylori and Graves’ disease suggests a possible role of this bacterium in the onset and/or the maintenance of the disease. “
“Helicobacter pylori infections and clinical outcome learn more are dependent on sophisticated interactions between the bacteria and its host. Crucial bacterial factors associated with pathogenicity

comprise a type IV secretion system encoded by the cag pathogenicity island, the effector protein CagA, the vacuolating cytotoxin (VacA), peptidoglycan, lipopolysaccharide (LPS), γ-glutamyl transpeptidase (GGT), protease HtrA, and the adhesins BabA, SabA, and others. The high number of these factors and allelic variation of the involved genes generates a highly complex scenario and reveals the difficulties in testing the contribution of each individual factor. Much effort has been put into identifying the molecular mechanisms associated with H. pylori-associated pathogenesis using human primary tissues, Mongolian gerbils, transgenic, knockout, and other mice as well as in vitro cell model systems. Interactions between bacterial factors and host signal transduction pathways seem to be critical for mediating the induction of pathogenic downstream processes and disease development. In this review article, we discuss the most recent progress in this research field.

Lactobacillus johnsonii MH-68 and L. salivarius subsp. salicinius AP-32 effectively suppress H. pylori viability, and when used as probiotics, they may help decrease the occurrence of gastritis, and even reduce the risk of H. pylori

infection. “
“Background:  viral and bacterial antigens have been suspected to be able to mimic the antigenic profile PLX-4720 clinical trial of the thyroid cell membrane and to play an important role in the onset of the autoimmune diseases, such as Graves’ disease and Hashimoto thyroiditis. The Helicobacter pylori infection is worldwide diffused and is present in the developed countries up to 50% of the population. The presence of the cytotoxin-associated gene A antigens identifies the most virulent strains of the bacterium. Previous studies have demonstrated the possible correlation between the Helicobacter pylori and Hashimoto’s thyroiditis but these results are controversial. Aims:  We studied the prevalence rate of this bacterium in the Graves’ disease and two selected subgroups such as the hyperthyroid patients, at the first time of diagnosis, and the euthyroid methimazole-treated patients. Materials and Methods:  We analyzed Helicobacter pylori in fresh stool samples with an enzyme immunoassay method and the presence of cytotoxin-associated gene A antigens with a serological test. Results:  Our results show that a significative increased rate of prevalence is present in Graves’ patients, when the disease is ongoing,

with an overall prevalence of the strains expressing the cytotoxin-associated gene A antigens compared to the control group. Conclusions:  The association between the selleck chemicals Helicobacter pylori and Graves’ disease suggests a possible role of this bacterium in the onset and/or the maintenance of the disease. “
“Helicobacter pylori infections and clinical outcome selleck screening library are dependent on sophisticated interactions between the bacteria and its host. Crucial bacterial factors associated with pathogenicity

comprise a type IV secretion system encoded by the cag pathogenicity island, the effector protein CagA, the vacuolating cytotoxin (VacA), peptidoglycan, lipopolysaccharide (LPS), γ-glutamyl transpeptidase (GGT), protease HtrA, and the adhesins BabA, SabA, and others. The high number of these factors and allelic variation of the involved genes generates a highly complex scenario and reveals the difficulties in testing the contribution of each individual factor. Much effort has been put into identifying the molecular mechanisms associated with H. pylori-associated pathogenesis using human primary tissues, Mongolian gerbils, transgenic, knockout, and other mice as well as in vitro cell model systems. Interactions between bacterial factors and host signal transduction pathways seem to be critical for mediating the induction of pathogenic downstream processes and disease development. In this review article, we discuss the most recent progress in this research field.

[15, 16] HCV-induced modulations of lipid metabolism include increased cellular triglyceride and cholesterol storage to facilitate viral replication.[15-17] Furthermore,

both cholesterol[18] and lipoprotein[19, 20] receptors have been implicated as HCV entry factors. Viral particle assembly and secretion also use components of the very-low density lipoprotein (VLDL) pathway.[21] Given this intimate link between HCV and hepatic metabolism, we examined the role of miR-27 in HCV pathogenesis and, herein, establish its role in HCV-induced hepatic steatosis. The pFK-I389luc/NS3-3′/5.1 Alectinib solubility dmso plasmid containing the HCV subgenomic replicon (genotype 1b isolate Con1, GenBank accession no. AJ242654) and the NS5B active site mutant replicon were kind gifts from Dr. Ralf Bartenschlager (Institute of Hygiene, University of Heidelberg, Heidelberg, Germany). The

Huh7.5 cell line stably expressing the full-length HCV genotype 1b replicon with a S2204I adaptive mutation in NS5A (Huh7.5-FGR) was a kind gift from Dr. Charles M. Rice (Rockefeller University, New York, NY) and Apath (St. Louis, MO). Imaged cells were washed twice with phosphate-buffered saline (PBS), followed by a 15-minute incubation at room temperature with fixing solution (4% formaldehyde, 4% sucrose, 1 mL). The fixed cells were washed twice with PBS for 3 minutes and find more then stored at 4°C in PBS prior to imaging. The imaging and subsequent quantitative voxel analysis of TG content was performed as described.[22, 23] Lipid droplet (LD) sizing/counting was performed using ImageJ (NIH, Bethesda, MD). Liver frozen sections (at 4 μm thickness) were fixed in 4% freshly made paraformaldehyde for 30 minutes, followed by 5 minutes learn more PBS rinse to remove excess paraformaldehyde. Fixed slides were then permeabilized in PBS containing 0.5% Triton X-100 for 10 minutes and blocked in PBS with 10% normal goat serum for 1 hour. The 1/100 diluted primary rabbit monoclonal antibody specifically recognizing human Cytokeratin 18 (CK-18) (Abcam, Cambridge, MA) was applied to the liver sections

and incubated at 4°C overnight. The next day liver sections were incubated in secondary antibody cocktail, including Alexa Fluor 488-conjugated goat antirabbit and DAPI, for 1 hour in the dark. After 3 washes of PBS, slides were immersed in Oil Red O working solution (freshly prepared in 30% triethyl-phosphate),[24] for 30 minutes in the dark, followed by 3 rinses with distilled water. Finally, slides were rinsed in the dark for 10 minutes, air dried, mounted with prolong gold mounting medium (Invitrogen), and coverslipped. Samples were examined with a Leica TCS SP5 confocal microscope. Oil Red O staining of lipids was visualized at far-red wavelength: 633 (ex) and 647 (em). Images were processed using LAS AF Lite software.

[15, 16] HCV-induced modulations of lipid metabolism include increased cellular triglyceride and cholesterol storage to facilitate viral replication.[15-17] Furthermore,

both cholesterol[18] and lipoprotein[19, 20] receptors have been implicated as HCV entry factors. Viral particle assembly and secretion also use components of the very-low density lipoprotein (VLDL) pathway.[21] Given this intimate link between HCV and hepatic metabolism, we examined the role of miR-27 in HCV pathogenesis and, herein, establish its role in HCV-induced hepatic steatosis. The pFK-I389luc/NS3-3′/5.1 ACP-196 plasmid containing the HCV subgenomic replicon (genotype 1b isolate Con1, GenBank accession no. AJ242654) and the NS5B active site mutant replicon were kind gifts from Dr. Ralf Bartenschlager (Institute of Hygiene, University of Heidelberg, Heidelberg, Germany). The

Huh7.5 cell line stably expressing the full-length HCV genotype 1b replicon with a S2204I adaptive mutation in NS5A (Huh7.5-FGR) was a kind gift from Dr. Charles M. Rice (Rockefeller University, New York, NY) and Apath (St. Louis, MO). Imaged cells were washed twice with phosphate-buffered saline (PBS), followed by a 15-minute incubation at room temperature with fixing solution (4% formaldehyde, 4% sucrose, 1 mL). The fixed cells were washed twice with PBS for 3 minutes and selleck compound then stored at 4°C in PBS prior to imaging. The imaging and subsequent quantitative voxel analysis of TG content was performed as described.[22, 23] Lipid droplet (LD) sizing/counting was performed using ImageJ (NIH, Bethesda, MD). Liver frozen sections (at 4 μm thickness) were fixed in 4% freshly made paraformaldehyde for 30 minutes, followed by 5 minutes selleck chemical PBS rinse to remove excess paraformaldehyde. Fixed slides were then permeabilized in PBS containing 0.5% Triton X-100 for 10 minutes and blocked in PBS with 10% normal goat serum for 1 hour. The 1/100 diluted primary rabbit monoclonal antibody specifically recognizing human Cytokeratin 18 (CK-18) (Abcam, Cambridge, MA) was applied to the liver sections

and incubated at 4°C overnight. The next day liver sections were incubated in secondary antibody cocktail, including Alexa Fluor 488-conjugated goat antirabbit and DAPI, for 1 hour in the dark. After 3 washes of PBS, slides were immersed in Oil Red O working solution (freshly prepared in 30% triethyl-phosphate),[24] for 30 minutes in the dark, followed by 3 rinses with distilled water. Finally, slides were rinsed in the dark for 10 minutes, air dried, mounted with prolong gold mounting medium (Invitrogen), and coverslipped. Samples were examined with a Leica TCS SP5 confocal microscope. Oil Red O staining of lipids was visualized at far-red wavelength: 633 (ex) and 647 (em). Images were processed using LAS AF Lite software.

RESULTS: The search identified 496 citations, including 7 retrospective series, and 692 patients met eligibility criteria. The use of duct-to-duct anastomosis was not associated with a significant difference in clinical outcomes, including 1-year recipient survival rates (OR 1.02; 95% CI 0.65–1.60; p=0.95), 1-year graft survival rates (OR 1.11; 95% CI 0.72–1.71; p=0.64), risk of biliary leaks (OR of 1.23; 95% confidence interval [CI] 0.59–2.59; p=0.33), risk of biliary strictures (OR 1.99; 95% CI 0.98–4.06; p=0.06),

or rate of recurrence of PSC (OR 0.94; 95% CI 0.19–4.78; p=0.94). CONCLUSION: The current evidence presented herein does not support the universal preference of Roux-en-Y choledochojejunostomy for all patients undergoing OLT for PSC, as there is no significance difference XL184 in vitro in clinical outcomes between well-selected patients who receive duct-to-duct anastomosis versus Roux-en-Y loops. Selection will continue to be made by the surgeon at time of LT with or without pre-LT cholangiography, based on donor and recipient characteristics, but barring other factors such as a diseased common bile duct, our results suggest duct-to-duct anastomosis should be preferred. Disclosures: The following people have nothing to disclose: Malcolm M. Wells, Kristopher Croome, Erin Boyce, Natasha check details Chandok [Background] Glucose storage

diseases (GSD) show growth retardation, but there are a few reports about the growth pattern and the effect of portocaval shunt (PCS) and liver transplantation (LT) for GSD patients. This study aims to analyze the change of physical growth and 2nd sexuality after PCS or/and LT in GSD type I. [Patients and Methods] We reviewed retrospectively 56 patients (M : F=38 : 18) with GSD type I

between 1975 and 2013. Among them, 13 underwent LT (at median 14 year-old, range 9–21, LT group) and 17 with PCS (10, 4–12, PCS group). Their data were compared with the normal data of CDC & WHO and the height standard deviation scores (Z-scores) and its annual differences (delta Z-score) were calculated click here and presented. And a modified delta Z-score (m-delta Z-score) was defined an annual difference between Z-score of operation group and the cross-sectional median Z-score of non-operation group. [Results] Regardless of height at birth, Z score for their height was sharply decreased to less than zero within 4 years in all patients. After operations, there was a spurt of height in the postoperative period. The median Z-score was −3.1 in LT group and −2.7 in PCS group at the time of operations. They caught up growth up to Z=−0.25 at postoperative 4 years in LT group and to Z=−0.6 at postoperative 6 years in PCS group. Delta Z-score were +0.4 and +0.6 respectively in the postoperative 1st year after LT or PCS. Then delta Z-score decreased annually.

Ascaris lumbricoides seropositivity correlated with elevated IgE and anti-inflammatory Th2-IgG1 responses to H. pylori, while Toxoplasma gondii seropositivity was linked to elevated IgE, pro-inflammatory Th1-IgG2, IgG3, and IgG4 responses to H. pylori. These infections may have an impact on inflammatory responses to H. pylori and may partially explain differences in gastric cancer risk in Colombia [19]. Hirsch et al. [20] were able to detect H. pylori DNA by PCR in several plaque and root canal samples, and cultured H. pylori from two root canals, suggesting that root canals of endodontic-infected deciduous teeth may be a reservoir for H. pylori

and serve as a potential source of transmission. Mother-to-child transmission p38 MAPK signaling was suspected in 2 of 3 families, and father–child transmission in one family in the study by Osaki et al. [21] using multilocus sequence typing (MLST) of total DNA extracted from fecal specimens. Helicobacter pylori infection is recognized as a cause of gastritis and peptic ulcer disease (PUD) in children. Symptoms, except those related to PUD, are nonspecific. Only a small proportion of children develop symptoms and clinically relevant gastrointestinal disease [22]. Dore et al. [9], in a cross-sectional sero-epidemiologic study,

found that nausea or vomiting and diarrhea were significantly associated with H. pylori infection (OR 2.2 and 2.1, respectively), but not with abdominal pain or heartburn. Perforated ulcer is rare, but several cases learn more of peritonitis secondary to duodenal perforation have been described [23, 24]. Helicobacter pylori infection not only causes damage to the gastric epithelium, it also plays a potential pathogenic role in several extraintestinal diseases. Bradbeer et al. [25] described the resolution of recurrent headaches in a child this website after eradication of H. pylori infection and postulated this possible association. Controversy exists concerning the relationship of H. pylori infection and

somatic growth retardation in children. Dehghani et al. [26] evaluated the relationship between H. pylori infection and growth parameters in Indian children and concluded that symptomatic infection does not appear to influence linear growth. The gastrointestinal hormone ghrelin is a gut–brain peptide that regulates food intake in humans and has strong growth hormone-releasing activity. Decreased appetite in H. pylori-infected children has been related to low plasma ghrelin levels which returned to normal after H. pylori eradication. Deng et al. [27] evaluated plasma and gastric ghrelin production as well as body mass index (BMI), before and after treating H. pylori infection in 50 Chinese children, divided into two groups based on the success of H. pylori treatment. They found that plasma and tissue ghrelin levels increased substantially after treatment in the group with therapeutic success, but only minor changes were observed in the group with treatment failure.