Determining the prevalence of Escherichia coli, Salmonella, and shiga toxin-producing Escherichia coli in manure of dairy lagoons.

AIM: The aim of this study was to determine the prevalence of microbial pathogens in manure of dairy lagoons in California. METHODS AND RESULTS: To determine pathogens in dairy manure stored in anaerobic lagoons of dairy farm, an extensive field study was conducted across California to sample manure from 20 dairy farms. Samples were analyzed to determine the prevalence of indicator E. coli, Shiga toxin producing E. coli (STEC), Salmonella, and E. coli O157:H7. To test the E. coli, STEC, and Salmonella, we used agar culture-based method followed by polymerase chain reaction (PCR) method. In addition, a real- time PCR based method was used to determine the presence of E coli O157:H7. Study demonstrated that the prevalence of Salmonella in manure sample is lower than E. coli. The presence of Salmonella was found in 2.26% of the samples, and both the culture-based and PCR methods yielded comparable outcomes in detecting Salmonella. Moreover, approximately 11.30% of the total samples out of the 177 were identified as positive for STEC by qPCR. CONCLUSION: These findings demonstrate that indicator E. coli are abundantly present in anaerobic lagoons. However, the presence of STEC, and Salmonella is substantially low.

Two Cases of Exacerbation of Asthma during Treatment with Enfortumab Vedotin.

Enfortumab vedotin is an antibody-drug conjugate against nectin-4 that is recently being used in the management of patients with urothelial carcinoma. The common adverse events include rashes, peripheral neuropathy, and hyperglycemia. Only a few cases of associated respiratory symptoms have been reported. Herein, we describe 2 patients with advanced urothelial carcinoma who experienced asthma exacerbation after initiating enfortumab vedotin treatment. Both patients improved with inhalation therapy. Since nectin-4 is expressed in the tracheal epithelium, its association with asthma is likely. This study highlights that clinicians should caution patients with a history of asthma against the worsening of respiratory symptoms when enfortumab vedotin is administered.

Relationship between the Responsiveness of Amyloid ß Protein to Platelet Activation by TRAP Stimulation and Brain Atrophy in Patients with Diabetes Mellitus.

Type 2 DM is a risk factor for dementia, including Alzheimer's disease (AD), and is associated with brain atrophy. Amyloid ß protein (Aß) deposition in the brain parenchyma is implicated in the neurodegeneration that occurs in AD. Platelets, known as abundant storage of Aß, are recognized to play important roles in the onset and progression of AD. We recently showed that Aß negatively regulates platelet activation induced by thrombin receptor-activating protein (TRAP) in healthy people. In the present study, we investigated the effects of Aß on the TRAP-stimulated platelet activation in DM patients, and the relationship between the individual responsiveness to Aß and quantitative findings of MRI, the volume of white matter hyperintensity (WMH)/intracranial volume (IC) and the volume of parenchyma (PAR)/IC. In some DM patients, Aß reduced platelet aggregation induced by TRAP, while in others it was unchanged or rather enhanced. The TRAP-induced levels of phosphorylated-Akt and phosphorylated-HSP27, the levels of PDGF-AB and the released phosphorylated-HSP27 correlated with the degree of platelet aggregability. The individual levels of not WMH/IC but PAR/IC was correlated with those of TRAP-stimulated PDGF-AB release. Collectively, our results suggest that the reactivity of TRAP-stimulated platelet activation to Aß differs in DM patients from healthy people. The anti-suppressive feature of platelet activation to Aß might be protective for brain atrophy in DM patients.

Regular intake of cow's milk with oral immunotherapy improves statures of children with milk allergies.

BACKGROUND: Children who avoid cow's milk (CM) because of food allergy may show disturbed growth. Calcium insufficiency, in particular, was reported among those who completely avoided dairy products. We retrospectively examined whether oral immunotherapy (OIT) affected the stature of patients who had completely avoided CM owing to their severe CM allergy. METHODS: The CM-OIT group included subjects who had completely avoided milk their entire lives and were administered OIT between 2009 and 2013. The complete milk avoidance (CM-Avoid) group included subjects who were diagnosed with a CM allergy using oral food challenges between 2013 and 2014 who subsequently avoided CM completely. By examining clinical records and questionnaires, we investigated patient height changes over time. We calculated age- and sex-stratified height standard deviation scores (HtSDS) and analyzed changes in HtSDS retrospectively. The observation period was 1-2 years. To exclude pubertal growth spurts, we set the age criteria as less than 11 years in boys and less than 9 years in girls. RESULTS: We recruited 29 patients (19 boys) for the CM-OIT group and 20 (9 boys) for the CM-Avoid group. The patients' median ages at the start of the observation period were 7.5 years (6.1-9.6) for boys and 6.8 years (5.8-7.8) for girls in the CM-OIT group, and 5.4 years (5.0-7.5) for boys and 5.7 years (5.0-7.1) for girls in the CM-Avoid group. The initial HtSDS in the CM-OIT group was -0.31 (median) and increased to -0.22 (median) after OIT (p = 0.016). In contrast, there was no significant change in HtSDS for the CM-Avoid group. CONCLUSIONS: Physical growth of pediatric patients with severe CM allergies, who have avoided CM completely, could be improved by OIT for CM allergy.

＜Editors' Choice＞ Renewed Japanese spirometric reference variables and risk stratification for postoperative outcomes in COPD patients with resected lung cancer.

Although the lower limit of normal (LLN) of FEV1/FVC detects at-risk patients for postoperative outcomes among Japanese chronic obstructive pulmonary disease (COPD) patients with resected lung cancer, there was a lack of a Japanese reference equation to calculate the LLN of FEV1/FVC. Renewed Japanese spirometric reference variables might enable us to verify clinical impact of the LLN of FEV1/FVC among the Japanese population. To evaluate the clinical impact of the LLN of FEV1/FVC by using this renewed reference, data were retrospectively analyzed from 609 newly diagnosed lung cancer patients who had undergone thoracic surgery between 2006 and 2011. The combined assessment of the 0.70 fixed ratio and the LLN of the FEV1/FVC ratio classified the 609 subjects into the COPD (214 subjects), non-COPD (337 subjects), and in-between (58 subjects) groups, respectively. All of the relative odds ratios (ORs) of postoperative outcomes for the comparison between the in-between and non-COPD groups did not show significant confidence intervals (CIs). On the other hand, the adjusted ORs of postoperative outcomes for the COPD group versus the non-COPD group were 2.840 (95% CI: 1.824-4.421) for prolonged oxygen therapy (POT), 1.836 (95% CI: 1.166-2.890) for prolonged postoperative stays, and 1.637 (95% CI: 1.007-2.663) for combined complications. Adjusted comparisons of POT between the in-between and COPD groups also showed a significant relative OR of 2.984 (95% CI: 1.447-6.153). A standardized assessment of the LLN of FEV1/FVC by a renewed Japanese spirometric reference provides risk stratification for postoperative outcomes in the population.

Thin-section computed tomography-determined usual interstitial pneumonia pattern affects the decision-making process for resection in newly diagnosed lung cancer patients: a retrospective study.

BACKGROUND: There is only limited information on the impact of thin-section computed tomography (TSCT)-determined usual interstitial pneumonia (UIP) pattern in the decision-making for resection in newly diagnosed lung cancer patients. METHODS: In this retrospective analysis, data were reviewed from 499 newly diagnosed lung cancer patients who received bronchoscopy between 2010 and 2014. The clinical impact of TSCT-determined UIP pattern on the decision-making process for resection in this cohort was evaluated. RESULTS: The prevalence rate of TSCT-determined fibrosis was 14.8% (74/499 cases), 86.5% (64/74 cases) of which also had TSCT-determined emphysema. The fibrosis group comprised 40 patients with possible UIP and 34 patients with the UIP pattern. Among surgical candidates, the number of surgeries performed was lower in the fibrosis group (60.8%) than in the normal and emphysema groups (84.7 and 77.3%, respectively). Although the proportion of possible UIP did not differ between surgical candidates and patients with resected lung cancer, the proportion of UIP pattern in patients with resected lung cancer was decreased by 8.5%, compared to the surgical candidates. Although measurement of diffusing capacity of the lung for carbon monoxide (DLCO) was performed in more than 97% of patients with thoracic surgery, only 58% of patients without thoracic surgery had DLCO measurement. Multivariate analysis showed that the finding of UIP pattern independently affects the decision-making process for thoracic surgery. The adjusted odds ratios for the comparison between the patients without fibrosis and the patients with UIP pattern was 0.266 (95% confidence intervals: 0.087-0.812). CONCLUSIONS: The presence of TSCT-determined UIP pattern might independently affect the decision-making process for proposing thoracic surgery with curative intent.

Heated egg yolk challenge predicts the natural course of hen's egg allergy: a retrospective study.

BACKGROUND: Children do not always outgrow hen's egg allergies in early childhood. Because egg yolks are less allergenic than egg whites, we performed an oral food challenge with heated egg yolk slightly contaminated with egg white (EYSEW OFC) in infants allergic to hen's egg. We hypothesized that the EYSEW OFC results would predict the egg allergy's natural course. METHODS: We retrospectively reviewed participants with hen's egg allergy who underwent their first EYSEW OFC at 12-23 months of age between 2004 and 2010. Participants who passed the first EYSEW OFC were defined as EYSEW-tolerant, and participants who failed the OFC were defined as EYSEW-reactive. Participants who passed the EYSEW OFC underwent an OFC with half of a heated whole egg (WE OFC). Participants who passed a WE OFC were defined to be heated hen's egg-tolerant. Participants who failed the EYSEW OFC or the WE OFC underwent another OFC at least 6 months later. We compared tolerance to heated hen's egg at 36 months after the first EYSEW OFC between EYSEW-tolerant and EYSEW-reactive participants. Univariate and multivariate logistic regression analyses were conducted. RESULTS: Of the 197 included participants (median age: 18.3 months; range: 12.1-23.8 months), 179 (90.9 %) were EYSEW tolerant and 18 (9.1 %) were EYSEW reactive. At 36 months after the first EYSEW OFC, 164 EYSEW-tolerant (91.6 %) and 12 EYSEW-reactive participants (66.7 %) achieved heated hen's egg tolerance. In the univariate logistic regression analyses, EYSEW-reactive participants (crude odds ratio [OR], 5.5 [95 % confidence intervals [CI], 1.8-16.6]; p = 0.003) and those with baseline egg white sIgE levels (crude OR: 3.9 per ten-fold increase [95 % CI, 1.5-10.2]; p = 0.005) had greater odds of persistent allergy to hen's egg at 36 months after the first EYSEW OFC. In a multivariate logistic regression analysis after adjustment for baseline egg white sIgE, EYSEW-reactive participants had greater odds of persistent allergy to hen's egg than EYSEW-tolerant participants (adjusted OR: 4.6 [95 % CI, 1.5-15.0]; p = 0.003). CONCLUSIONS: Classifying infants who are allergic to hen's egg into EYSEW tolerant and EYSEW reactive groups was useful in determining prognosis.

Factors influencing sustainable efficacy of smoking cessation treatment with varenicline beyond nine months.

Pharmacological therapies play an important role in the success of interventions for smoking cessation; however, long-term follow-up studies with analysis of influencing factors are scarce. We examined the sustainable effects of smoking cessation therapy with varenicline, beyond nine months as well as the factors influencing effectiveness. Our sample consisted of 193 patients (126 men [68.2%], 67 women [31.8%], aged 26 to 85 years) who underwent varenicline therapy at the Nagoya University Hospital between January 2009 and October 2013. We examined their clinical records and also conducted a mail survey and evaluated success rates of smoking cessation therapy beyond nine months. Overall, 95.8% (185/193) of the patients had at least one complication. The response rate of questionnaires at the end of smoking cessation was 61.6% (119/193). The smoking cessation rate continued to decline for one year and leveled off afterwards. Smoking cessation rates tended to correlate with an increasing number of outpatient visits. Logistic regression analysis showed that two factors, young age and high Beck Depression Inventory-II (BDI-II) scores, were inversely correlated with success rates of smoking cessation. From the results of this study, aggressive intervention would needed for younger patients or patients with higher BDI-II scores.

Psychogenic nonepileptic seizures as a manifestation of psychological distress associated with undiagnosed autism spectrum disorder.

Psychogenic nonepileptic seizures (PNES) are observable changes in behavior or consciousness that are similar to epileptic seizures but are not associated with electrophysiologic changes. PNES occur in children with underlying psychological distress and are especially frequent in those with epilepsy. Because PNES are heterogeneous, comprehensive treatment tailored to each patient is required to reduce psychosocial stress. Currently, reports regarding children with PNES concomitant with autism spectrum disorder (ASD) do not exist, and effective treatment strategies for these children are lacking. In this case report, we describe a 10-year-old Japanese girl with undiagnosed ASD who developed PNES while undergoing treatment for benign childhood epilepsy with centrotemporal spikes. She exhibited hypersensitivity to sound and interpersonal conflicts caused by social communication deficits. The PNES symptoms improved shortly after our intervention, which was designed to reduce her distress caused by auditory hypersensitivity and impaired social communication, both characteristics of ASD. To the best of our knowledge, this is the first report describing PNES in a child with ASD. Our findings suggest that PNES can result from psychological distress in children with undiagnosed ASD and highlight the importance of examining ASD traits in patients with PNES.

New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies.

A number of studies have suggested that a large subset of children (approximately 70%) who react to unheated milk or egg can tolerate extensively heated forms of these foods. A diet that includes baked milk or egg is well tolerated and appears to accelerate the development of regular milk or egg tolerance when compared with strict avoidance. However, the indications for an oral food challenge (OFC) using baked products are limited for patients with high specific IgE values or large skin prick test diameters. Oral immunotherapies (OITs) are becoming increasingly popular for the management of food allergies. However, the reported efficacy of OIT is not satisfactory, given the high frequency of symptoms and requirement for long-term therapy. With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods.

Subclinical Manic Symptoms in Children with Autism Spectrum Disorder.

Background: Children with autism spectrum disorder (ASD) have varied comorbidities. With regard to comorbidity, there has been increasing interest in bipolar disorder (BP) in children. However, the prevalence of BP with ASD has varied because of the methodological differences used. Therefore the adequate criteria for determining BP in children are still debated. The purpose of this study is to identify reliable prevalence of BP and to evaluate a variety of subclinical BP symptoms in children with ASD. Methods: This is a cross-sectional and case-control study. The participants were 110 referred children aged 6-15 years: 46 with ASD (the case group), 64 without ASD (the control group). We used the strict operational criteria for diagnosing BP, and assessed the presence of subclinical BP symptoms using a semi-structured diagnostic interview. Results: None of the children were diagnosed with BP in the case group, although two children were diagnosed with BP in the control group. Based on the subclinical BP symptoms, the prevalence of elation/expansive mood and racing thoughts was significantly higher in the case group than in the control group: 26.1% versus 3.1% (p<.001) and 32.6% versus 9.4% (p=0.002), respectively. Conclusions: Our finding indicates that school-aged ASD children frequently present subclinical BP symptoms. It is important to be aware of over-diagnosis of BP, even though the children present subclinical BP symptoms, and to provide -the children with effective treatments.

Better management of wheat allergy using a very low-dose food challenge: A retrospective study.

BACKGROUND: Low-dose reactive wheat-allergic children are at a high risk of a positive oral food challenge (OFC). The present study aimed to evaluate whether the results of a very low-dose (VL) OFC would contribute to better wheat allergy management in this population. METHODS: We retrospectively reviewed wheat-allergic subjects who underwent a VL OFC with 2 g of udon noodles (equivalent to 53 mg of wheat protein) and had a previous allergic reaction to <15 g of udon noodles (equivalent to 400 mg of wheat protein) within 2 years before the OFC. Subjects who passed the OFC were defined as VL tolerant; those who failed were considered VL reactive. In VL tolerant subjects, the dose was increased to 15 g of udon noodles either during an OFC in our hospital or gradually at home. RESULTS: Of the 57 included subjects (median age, 2.9 years; range, 1.0-11.8 years), 32 (56%) were VL tolerant and 25 (44%) were VL reactive. Most reactions during the OFC could be treated with an antihistamine and/or a nebulized ß2 agonist. VL tolerant subjects consumed 2 g of udon noodles or a seasoning containing wheat. Within a year after the OFC, 18 VL tolerant subjects (56%), but no VL reactive subjects, were able to consume 15 g of udon noodles (p < 0.001). CONCLUSIONS: A VL OFC can shift the management of some low-dose reactive wheat-allergic children from complete avoidance to partial wheat intake.

A Single-Center, Case-Control Study of Low-Dose-Induction Oral Immunotherapy with Cow's Milk.

BACKGROUND: This study aimed to investigate the efficacy and safety of low-dose-induction oral immunotherapy (OIT) with 3 ml of milk, which is a lower target volume than is conventionally used. METHODS: Children aged ≥5 years with milk allergies [confirmed by oral food challenge (OFC) against 3 ml of milk] were enrolled. The OIT group was admitted to the hospital for 5 days for build-up. Subsequently, at home, the volume was gradually increased by up to a maximum of 3 ml every 5 days. While the OIT group ingested a small amount of milk every day, the control group completely eliminated their milk intake. Both groups underwent OFCs approximately 1 year later in order to assess their responsiveness to 3 ml and 25 ml of cow's milk. RESULTS: The OIT and control groups had no background differences; the proportion of patients unresponsive to 3 ml of milk after 1 year was 58.3% (7/12) and 13.8% (4/25), respectively (p = 0.018), while the proportion unresponsive to 25 ml of milk was 33.3% (4/12) and 0.0% (0/25), respectively (p = 0.007). Furthermore, a significant decrease in the casein-specific immunoglobulin E levels was seen after 12 months when compared to baseline in the OIT group (p = 0.033). Adverse allergic reactions were rare and most symptoms were mild. CONCLUSION: This study of a high-risk population reacting to very low amounts of milk showed that low-dose-induction OIT appeared effective for acquiring unresponsiveness to 3 ml and 25 ml of milk, with severe symptoms being rare, indicating that for improvement of food allergies, continuous intake of small amounts may be as effective as intake of larger amounts.

Better management of cow's milk allergy using a very low dose food challenge test: a retrospective study.

BACKGROUND: Low dose reactive cow's milk (CM) allergic children are at high risk of persistent CM allergy and a positive oral food challenge (OFC). The present study aimed to evaluate if the results of a very low dose (VL) OFC with these children contributes to better management of CM allergy. METHODS: We retrospectively reviewed subjects with CM allergy who underwent a VL OFC with 3 mL heated CM and had a previous allergic reaction to <25 mL heated CM in the 2 years before the OFC. Subjects who passed the OFC were defined as VL tolerant, and subjects who failed were defined as VL reactive. VL tolerant subjects increased the dose to 25 mL heated CM either during an OFC in our hospital or gradually at home. RESULTS: Of the 83 subjects (median age, 4.3 years; range, 1.0-12.9 years) who were included, 41 (49.4%) were VL tolerant, and 42 (51.6%) were VL reactive. Thirty-nine VL reactive subjects had skin and/or respiratory symptoms during the OFC. Most reactions could be treated with an antihistamine and/or a nebulized ß2 agonist. The VL tolerant subjects consumed 3 mL heated CM or 10 g butter. Within the year following the OFC, 18 VL tolerant subjects (45.0%), but none of the VL reactive subjects, were able to consume 25 mL heated CM (p < 0.001). CONCLUSIONS: A VL OFC allows the management of some low dose reactive CM allergic children to change from complete avoidance to partial intake of CM.

High Prevalence of Non-psychotic Delusions in Children with High-functioning Pervasive Develonmental Disorder.

BACKGROUND: Non-psychotic delusions are reported to be associated with depression and anxiety. When these delusions occur in high-functioning pervasive developmental disorder (HFPDD) children, they are often misdiagnosed as schizophrenia and have consequently been studied less. This study has three goals: to investigate the prevalence of non-psychotic delusions in HFPDD children, to test the hypothesis that HFPDD children are more likely to have non-psychotic delusions than non-HFPDD children, and to test the hypothesis that non-psychotic delusions are associated with depression and anxiety. METHODS: This is a cross-sectional and case-control study. The participants were 45 HFPDD children (cases) and 51 children without HFPDD (controls). Semi-structured interviews were conducted to assess the presence of non-psychotic delusions. We used the Child Behavior Checklist (CBCL) to assess levels of anxiety and depression. RESULTS: Of the cases, 62.2% had non-psychotic delusions, which was significantly higher than controls (25.5%, p<0.001, OR: 4.81, 95% CI: 2.01-11.51). Cases tended to score higher for internalizing problems (including anxiety and depression) on the CBCL than controls (69.8±9.4 vs 65.9±10.4, t= 1.9, p=0.062). Cases with non-psychotic delusions scored significantly higher for internalizing problems in CBCL than children without non-psychotic delusions (72.2±7.7 vs 65.7±10.7, t=2.4, p= 0.022). CONCLUSIONS: More than half of the HFPDD children were suffering from non-psychotic delusions, and these delusions were associated with anxiety and depression. Therefore, accurate diagnoses of non-psychotic delusions should be conducted for appropriate treatments to be prescribed.

Immunotherapy in food allergy: towards new strategies.

Allergen avoidance is the standard treatment for managing food allergies. Complete avoidance is difficult, and accidental exposure often occurs. Immunotherapy is a significant focus for treating food allergies, and oral immunotherapy (OIT) appears to be particularly effective in inducing desensitization. The majority of patients who receive OIT show increased threshold doses of their food allergen. The efficacy of OIT is different among food antigen, and milk OIT is relatively difficult to achieve tolerance. OIT may induce mild to moderate symptoms during the therapy, widespread acceptance of OIT for long-term therapy is unclear. Recently, novel immunotherapies for food allergies, such as sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) and using an anti-IgE monoclonal antibody (omalizumab), have been assessed. In addition, a combination of OIT with omalizumab, which was found to increase the threshold doses of the offending foods without producing adverse reactions, may be effective and useful in the treatment of food allergies. These treatments have been used only in research settings; further studies in large numbers of patients are needed to demonstrate their long-term safety and benefits in clinical practice.

Psychiatric comorbidity in children with high-functioning pervasive developmental disorder.

BACKGROUND: In previous studies for children with pervasive developmental disorder (PDD), the prevalence for psychiatric comorbidities has varied because of their methodological differences. In this research, our PDD subjects were strictly limited by age and IQ scores, and we utilized a semi-structured interview to diagnose their coexisting disorders. The purpose of this study is to identify reliable prevalence and types of psychiatric comorbidities in children with high-functioning PDD (HFPDD). METHODS: The subjects were 49 children aged 6-15 years with HFPDD. In order to diagnose the comorbidities among them, we used the Japanese version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version. RESULTS: Forty-eight cases (98%) met the criteria for at least one comorbidity. The median number of the present comorbidities per child was 2, and the mode was 2. Depression (37%), attention deficit hyperactivity disorder (49%), and oppositional defiant disorder (45%) were frequently observed. CONCLUSIONS: Our finding indicates the high prevalence of comorbidities and the variety of the comorbid disorders in children with HFPDD. It is important to be aware of those comorbid disorders to provide the children with effective treatments.

Clinical studies in oral allergen-specific immunotherapy: differences among allergens.

Oral immunotherapy (OIT) is a significant focus of treatment of food allergy. OIT appears to be effective in inducing desensitization, however, patients receiving OIT frequently developmild/moderate symptoms during the therapy. It has not been clearly established whether the clinical tolerance induced by OIT resembles natural tolerance. According to our data, the efficacy of OIT is different among food antigens, and it is comparatively difficult to achieve the clinical tolerance in milk OIT. Moreover, the definitive evidence of efficacy and safety with long-term therapy is limited. Further studies need to be offered to patients in clinical practice. Recently, novel treatments for food allergy, sublingual and epicutaneous immunotherapy, and combination treatment with an anti-IgE monoclonal antibody (omalizumab), have been examined in some studies. OIT combined with omalizumab increased the threshold doses of food without adverse reactions and may be of benefit in food allergy treatment. More studies are needed to demonstrate long-term safety and treatment benefits in a larger patient cohort.