[Retrospective study on the diagnosis, treatment, and follow-up of 85 cases of hypophosphatemic rickets in children]. / 85ä¾‹ä½Žè¡€ç£·æ€§ä½å»ç— æ‚£å„¿è¯Šæ–­ã€æ²»ç–—ä¸Žéšè®¿çš„å›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To study the diagnosis, treatment, and complications of hypophosphatemic rickets (HR) in children, explore effectiveness evaluation indicators for the disease, and understand the pattern in height growth among these patients. METHODS: A retrospective analysis of the initial clinical data and five-year follow-up data of 85 children with HR treated at Children's Hospital of Nanjing Medical University from January 2008 to December 2022. RESULTS: Among the 85 children with HR, there were 46 males (54%) and 39 females (46%). The age at initial diagnosis ranged from 6 months to 13 years and 9 months, with a median age of 2.75 years. The average height standard deviation score was -2.0±1.1. At initial diagnosis, children exhibited reduced blood phosphate levels and elevated alkaline phosphatase (ALP), with 99% (84/85) presenting with lower limb deformities. The positive rate for PHEX gene mutations was 93% (55/59). One year post-treatment, there was a significant reduction in ALP levels and the gap between the lower limbs (P<0.05). The fastest height growth occurred in the first year after treatment, at 8.23 cm/year, with a peak height velocity (PHV) phase lasting about two years during puberty. The height increased by 9-20 cm in male children during the PHV stage and 10-15 cm in female children. Major complications included nephrocalcinosis and hyperparathyroidism. The incidence rate of nephrocalcinosis in the first year after treatment was 55% (22/40), which increased with the duration of the disease (P<0.001); an increased urinary phosphate/creatinine ratio was positively associated with a higher risk of nephrocalcinosis (OR=1.740, P<0.001). The incidence of hyperparathyroidism in the first year after treatment was 64% (27/42). CONCLUSIONS: For children presenting with lower limb deformities, short stature, and slow growth, early testing for blood levels of phosphate, calcium, and ALP, along with imaging examinations of the lower limbs, can aid in the early diagnosis of HR. Genetic testing may be utilized for definitive confirmation when necessary. ALP combined with improvements in skeletal deformities and annual height growth can serve as indicators of therapeutic effectiveness for HR. Compared to normal children, children with HR demonstrate a lower height increase during the PHV phase, necessitating close follow-up and timely adjustment of treatment plans Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 677-682.

Meta-Analysis of Efficacy of Platelet-Rich Plasma Combined with Minoxidil for Androgenetic Alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is a prevalent type of hair loss that impacts individuals of both genders. Platelet-rich plasma (PRP) and minoxidil have been employed as therapeutic interventions for AGA, yet the efficacy of their concurrent use remains ambiguous. OBJECTIVE: To perform a comprehensive review and meta-analysis aimed at evaluating the effectiveness of platelet-rich plasma (PRP) in combination with minoxidil for the treatment of androgenetic alopecia (AGA). METHODS: We conducted a comprehensive search of the databases PubMed, Embase, Web of Science, and Cochrane Library, encompassing their complete records up until December 2023. Eligible studies were randomized controlled trials that compared the combination of PRP and minoxidil with minoxidil or PRP alone in patients with AGA. The primary outcome measure was the change in hair growth as assessed by the hair density or hair thickness. Secondary outcome measures included patient satisfaction, and global photographic assessment. RESULTS: A total of 6 studies involving 343 participants were included in this meta-analysis. The results showed that PRP combined with minoxidil significantly improved hair growth compared to minoxidil or PRP alone. The pooled analysis demonstrated a significant increase in hair density (weighted mean difference [WMD] = 9.14; 95% confidence interval [CI]: 6.57-11.70) and hair diameter (WMD = 4.72; 95% CI 3.21-6.23) in the PRP combined with minoxidil group. Moreover, patients receiving PRP combined with minoxidil reported higher satisfaction rates compared to those using minoxidil or PRP alone. CONCLUSIONS: This meta-analysis suggests that PRP combined with minoxidil is an effective treatment for AGA, providing significant improvement in hair growth and patient satisfaction. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XII - Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA.

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as "conditional" following the GRADE approach due to the very low certainty about the health effects based on the available evidence. Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers' values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

Changes in risk factors for food sensitization in early life: Analysis over a period of 10 years.

Background: Although epidemiological trends of childhood food sensitization (FS) in IgE-mediated food allergy were reported in China, few studies have examined at changes in its risk factors. Objective: To investigate the change in early-life risk factors associated with childhood food sensitization during 2009-2019 in China. Methods: Data from two cross-sectional surveys conducted in 2009 and 2019 (401 and 513 children, respectively) were analyzed. The results of skin prick tests and information on food sensitization-related risk factors in children were summarized, including family history of atopic disease (FHA), demographic characteristics, method of delivery, feeding patterns, sibship size, pet ownership, and vitamin D supplementation. Binary logistic regression was used to calculate the odds ratio and the regression coefficient ß-value of risk factors in the 2009 and 2019 surveys separately. Then, coefficient ß-value differences between the two surveys were analyzed by the bdiff command in STATA to describe the change in risk factors over 10 years. Results: The 2009 survey revealed that FHA, age, only child, and feeding patterns were associated with food sensitization. The 2019 survey showed that food sensitization was affected by age, sex, and feeding patterns. However, from 2009 to 2019, the probability of food sensitization in the only-child group significantly increased by 226.0% (ß-value difference = 0.81, P = 0.024) and decreased by 65.0% in female children (ß-value difference = -1.06, P = 0.008). The effect of age on food sensitization decreased by 50.0% (ß-value difference = -0.69, P < 0.001) over 10 years. Conclusion: The effect of FHA and common lifestyle factors on food sensitization did not significantly change during 2009-2019. However, the influence of demographic characteristics on food sensitization has changed since 2009; that is, older age, male gender, and only child are more likely to develop food sensitization, which needs to be considered in future epidemiological surveys. Clinical Trial Registration: http://www.chictr.org.cn/, identifier ChiCTR1900024338.

The role of plasma cortisol in dementia, epilepsy, and multiple sclerosis: A Mendelian randomization study.

Background: Many clinical studies have shown a correlation between plasma cortisol and neurological disorders. This study explored the causal relationship between plasma cortisol and dementia, epilepsy and multiple sclerosis based on Mendelian randomization (MR) method. Methods: Data were taken from the summary statistics of a genome-wide association study, FinnGen consortium and United Kingdom Biobank. Dementia, epilepsy, and multiple sclerosis were used as outcomes, and genetic variants associated with plasma cortisol were used as instrumental variables. The main analysis was performed using the inverse variance weighted method, and the results were assessed according to the odds ratio (OR) and 95% confidence interval. Heterogeneity tests, pleiotropy tests, and leave-one-out method were conducted to evaluate the stability and accuracy of the results. Results: In two-sample MR analysis, the inverse variance weighted method showed that plasma cortisol was associated with Alzheimer's disease (AD) [odds ratio (95% confidence interval) = 0.99 (0.98-1.00), P = 0.025], vascular dementia (VaD) [odds ratio (95% confidence interval) = 2.02 (1.00-4.05), P = 0.049)], Parkinson's disease with dementia (PDD) [odds ratio (95% confidence interval) = 0.24 (0.07-0.82), P = 0.023] and epilepsy [odds ratio (95% confidence interval) = 2.00 (1.03-3.91), P = 0.042]. There were no statistically significant associations between plasma cortisol and dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) and multiple sclerosis. Conclusion: This study demonstrates that plasma cortisol increase the incidence rates of epilepsy and VaD and decrease the incidence rates of AD and PDD. Monitoring plasma cortisol concentrations in clinical practice can help prevent diseases, such as AD, PDD, VaD and epilepsy.

Comparative efficacy and safety of antidepressant therapy for the agitation of dementia: A systematic review and network meta-analysis.

Background: Dementia is a clinical syndrome commonly seen in the elderly individuals. With the prevalence of dementia, the incidence of neuropsychiatric symptoms in dementia patients is increasing annually. Agitation, as one of the neuropsychiatric symptoms, has a serious impact on the quality of life of patients with dementia. Several antidepressant drugs have been shown to be effective for treating agitated behavior symptoms in patients with dementia, but there are no direct comparisons among those drugs. Therefore, we carried out a network meta-analysis (NMA) to examine the efficacy and safety of those antidepressant drugs. Methods: We searched eight databases (PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, China National Knowledge Infrastructure, VIP Database and China biomedical literature service) from their inception to 6 November 2022. Randomized controlled trials (RCTs) reporting the efficacy and safety of antidepressant drugs in treating agitated behavior symptoms in patients with dementia were included in our analysis. The quality assessment was carried out by two researchers individually and the analysis was based on the frequency method. Results: Twelve articles with 1,146 participants were included in our analysis. Based on the outcome of the agitation score, treatment with citalopram (standardized mean difference, SMD = -0.44, 95% confidence interval, 95% CI = -0.72 to -0.16) showed significant benefits over the placebo group. Treatment with trazodone (odds ratio, OR = 4.58, 95% CI = 1.12-18.69) was associated with a higher risk of total adverse events compared with a placebo treatment. Conclusion: Among the antidepressant drugs included in this study, treatment with citalopram was probably the only optimal intervention, when considering the improvement from baseline to the end of the intervention, and there was not a statistically significant difference in safety when compared with a placebo treatment. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: PROSPERO, CRD42022320932.

Mental health and psychosocial problems among laboratory technicians in response to the COVID-19 pandemic in Hebei, China.

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, an increased mental burden has been widely reported among medical health workers such as physicians and nurses. However, data on laboratory technicians exposed to COVID-19 have rarely been published. The aim of this study was to assess the magnitude of psychological symptoms among laboratory technicians and analyze potential risk factors associated with these symptoms. Methods: A cross-sectional online survey was performed via the Wenjuanxing platform (a professional online questionnaire platform) (https://www.wjx.cn/mobile/statnew.aspx) to investigate the mental health of laboratory technicians during the COVID-19 pandemic in Hebei, China from October 4, 2021, to November 3, 2021. The online questionnaire included demographic and occupational characteristics data of responders, and the Symptom Check List-90-Revised (SCL90-R)was used to quantify the magnitude of psychological symptoms among laboratory technicians. Participants' demographic and occupational characteristics were analyzed using descriptive statistical analyses. Chi-square tests were applied to compare the severity of each symptom between two or more groups. A binary logistic regression model was developed to identify the predictors of laboratory technicians' mental health in response to the COVID-19 pandemic, and outcomes are presented as odds ratios and 95% confidence interval. Statistical analysis was performed using SPSS version 21 (SPSS, New Orchard Road, Armonk, New York, USA). Results: A total of 3081 valid questionnaires were collected. Of these 3081 participants, 338 (11.0%) reported a total SCL90-R score >160, which indicated positive psychological symptoms. Among the 338 participants who reported psychological problems, most of them were mild symptoms. Several factors associated with mental health problems in laboratory technicians during COVID-19 were found, which include a history of physical and/or psychological problems (all 10 symptoms p < 0.001), more than 10 years of work experience (depression symptoms: OR = 2.350, p = 0.024; anxiety symptoms: OR = 2.642, p = 0.038), frontline work (depression symptoms: OR = 1.761, p = 0.001; anxiety symptoms: OR = 2.619, p < 0.001; hostility symptoms: OR = 1.913, p = 0.001), participant in more than 3 times large-scale SARS-CoV-2 screenings and more than 36 h per week in SARS-CoV-2 nucleic acid testing. Conclusion: A portion of laboratory technicians reported experiencing varying levels of psychological burden. During the COVID-19 pandemic, multiple interventions should be developed and implemented to address existing psychosocial challenges and promote the mental health of laboratory technicians.

The comparison of skin prick test, serological specific IgE test and solid phase immunoassay in the diagnosis of infantile allergic diseases.

BACKGROUND: This retrospective study was designed in order to compare the usefulness of skin prick tests, serological specific IgE tests and solid phase immunoassays in the diagnosis of infantile allergic diseases. METHODS: Two hundred infants with allergic diseases (120 infants with eczema and 80 infants with asthma), diagnosed in the Pediatric Clinic of our hospital between June of 2011 and June of 2016, were selected to participate in the study. 100 healthy infants were included in a control group. All infants received a skin prick test, a serological specific IgE test or a solid phase immunoassay. A total of 38 allergens were used for the infants receiving skin prick test. The IgE in the serum samples of infants was detected by immunoblotting. And, allergens were detected by solid phase immunoassay in the infants receiving solid phase immunoassay. The positive predictive value, negative predictive value, specificity and sensitivity for these 3 diagnostic methods were analyzed after generating a ROC curve. RESULTS: In the eczema group, the AUCs (the area under the ROC curve) for skin prick test, serological specific IgE test and solid phase immunoassay were 0.8685±0.0187, 0.8137±0.024 and 0.9682±0.0358, respectively. The sensitivities for skin prick test, serological specific IgE test and solid phase immunoassay were 85.70%, 83.62% and 88.72%, respectively. And, the specificities were 74%, 68% and 83%, respectively. The positive predictive values were 87.27%, 92.37% and 90.00%; and the negative predictive values were 57.04%, 51.11% and 78.15%, respectively. In the asthma group, the AUCs for skin prick test, serological specific IgE test and solid phase immunoassay were 0.8186±0.0161, 0.8037±0.0241 and 0.952±0.0421, respectively. The sensitivities for skin prick test, serological specific IgE test and solid phase immunoassay were 84.70%, 88.62% and 96.72%, respectively. The specificities were 76%, 64% and 81%, respectively; the positive predictive values were 81.34%, 85.59% and 84.54%, respectively. The negative predictive values were 69.29%, 67.14% and 70.08%, respectively. CONCLUSIONS: While all three methods were effective in the diagnosis of infantile allergic diseases, the solid phase immunoassay was superior to the other two methods, as evidenced by the obtained values and we recommend it for clinical application as a goal standard.

The incidence of post-traumatic stress disorder following traumatic childbirth: A systematic review and meta-analysis.

BACKGROUND: Although birth trauma may be a risk factor for postpartum post-traumatic stress disorder (PTSD), no systematic review regarding the incidence of postpartum PTSD in women with traumatic childbirth has been reported. OBJECTIVE: To estimate the incidence of PTSD in women following traumatic childbirth by systematically reviewing and synthesizing all available evidence. SEARCH STRATEGY: Six databases were searched using a combination of related terms for birth trauma and PTSD. SELECTION CRITERIA: Cohort and cross-sectional studies that were related to traumatic childbirth and PTSD were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened potentially relevant studies and extracted key data elements. A series of meta-analyses were conducted using STATA 17.0 software, with pooled incidence rates estimated using random effects models. MAIN RESULTS: A total of nine studies were included in this study. The pooled incidence of PTSD after traumatic childbirth was 19.4% (95% confidence interval 11.9%-26.5%). The incidence of PTSD varied with the scales used to assess traumatic birth and PTSD, evaluation times of PTSD after childbirth, and types of study participants. CONCLUSIONS: The incidence of PTSD in women with traumatic childbirth is about 19%, higher than the general obstetric population, suggesting that trauma-related care for them should be enhanced.

Trends in the contributions of atopic family history to pediatric food sensitization and allergy.

Objective: Family history of atopic diseases (FHA) contributes to food allergy (FA). But little is known whether FHA primarily increases IgE-mediated, non-IgE-mediated FA, or both. And the trends in the contributions of FHA to food sensitization (FS) and FA remain unclear. We aim to clarify the associations among FHA, FS and FA and to understand the trends in the contributions of FHA to FS and FA. Methods: We used chi-square test and mediating effect model to analyze the associations among FHA, FS and FA through comparisons between two cross-sectional investigations on FA in children under 2 years old in 2009 and 2019. Results: In 2009 and 2019, the positive FHA proportion tended to be increasing without significance (28.9% to 31.6%, P = 0.39). Subgroup analysis showed the FS rate in FA group decreased significantly (37/39 to 44/62, P = 0.003). In 2009, the FS rate and FA prevalence were higher in FHA (+) group than in FHA (-) group (26% vs. 14.7%, P = 0.008 and 15% vs. 7.7%, P = 0.03), and FS had a complete mediating effect on the association between FHA and FA (Z = 2.54, P = 0.011), but the results lost significance in 2019. Conclusions: The association between FHA and FA was completely mediated by FS, which means FHA mainly increases IgE-mediated FA. And the contributions of FHA to FS and FA tended to be stabilized or even diminished, which means FHA alone could no longer be enough to screen high-risk children.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guideline update - XIV - Recommendations on CMA immunotherapy.

Background: The prevalence of cow's milk allergy (CMA) is approximately 2-4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of oral and epicutaneous immunotherapy for the treatment of IgE-mediated CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment. Results: After a careful review of the summarized evidence and thorough discussions the WAO guideline panel suggests: a) using oral immunotherapy with unheated cow's milk in those individuals with confirmed IgE-mediated CMA who value the ability to consume controlled quantities of milk more than avoiding the large adverse effects of therapy, b) not using oral immunotherapy with unheated cow's milk in those who value avoiding large adverse effects of therapy more than the ability to consume controlled quantities of milk, c) using omalizumab in those starting oral immunotherapy with unheated cow's milk, d) not using oral immunotherapy with baked cow's milk in those who do not tolerate both unheated and baked milk, and e) not using epicutaneous immunotherapy outside of a research setting. The recommendations are labeled "conditional" due to the low certainty about the health effects based on the available evidence. Conclusions: Clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable effects of oral immunotherapy for IgE-mediated CMA and integrate them with the patients' values and preferences before deciding on a treatment option. More robust research is needed to determine with greater certainty which interventions are likely to be the most beneficial with the least harms, and to develop safer, low-cost, and equitable treatments.

Exosomal Circular RNA as a Biomarker Platform for the Early Diagnosis of Immune-Mediated Demyelinating Disease.

Exosomes can pass through the blood-brain barrier and are present in the cerebrospinal fluid (CSF). The components in exosomes, such as DNA, RNA, protein, and lipids, change greatly and are closely related to disease progression. Circular RNA (circRNA) is stable in structure and has a long half-life in exosomes without degradation. Therefore, circRNA is considered an ideal biomarker and can be used to monitor a variety of central nervous system diseases. This study aimed to investigate the expression profiles of exosomal circRNA (exo-circRNA) in CSF from patients with immune-mediated demyelinating diseases to identify suitable biomarkers for the early diagnosis of immune-mediated demyelinating diseases. circRNA expression levels in exosomes obtained from five CSF samples from immune-mediated demyelinating disease patients and five paired CSF control samples were analyzed using a hybridization array. Hierarchical clustering analysis showed that 5,095 exo-circRNAs were differentially expressed between patients with immune-mediated demyelinating diseases and paired control samples. Of these exo-circRNAs, 26 were identified as significantly differentially expressed in CSF exosomes from patients with immune-mediated demyelinating diseases (FC ≥1.5 and p ≤ 0.05). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the upregulation or activation of protein tyrosine phosphatase receptor type F (PTPRF) and RAD23 homolog B, nucleotide excision repair protein (RAD23B) may be associated with the occurrence and development of immune-mediated demyelinating diseases. Then, a competing endogenous RNA network was constructed and centered on the most upregulated/downregulated exo-circRNAs to predict their function in immune-mediated demyelinating diseases. In addition, reverse transcription quantitative polymerase chain reaction results stating that hsa_circ_0087862 and hsa_circ_0012077 were validated in an independent cohort of subjects. Canonical correlation analysis results indicated a potential connection between exosomal hsa_circ_0012077 expression level and immunoglobulin G levels in CSF. Finally, the receiver operating characteristic (ROC) curve showed that when hsa_circ_0087862 or hsa_circ_0012077 was employed alone for diagnosing immune-mediated demyelinating diseases, the diagnostic accuracy was 100%. In conclusion, based on this study, exosomal hsa_circ_0087862 and hsa_circ_0012077 in CSF could be used as suitable biomarkers for the diagnosis of immune-mediated demyelinating disease based on their expression levels. Moreover, the upregulation or activation of PTPRF and RAD23B was potentially associated with the occurrence and development of immune-mediated demyelinating diseases.

DRAMP 2.0, an updated data repository of antimicrobial peptides.

Data Repository of Antimicrobial Peptides (DRAMP, http://dramp.cpu-bioinfor.org/ ) is an open-access comprehensive database containing general, patent and clinical antimicrobial peptides (AMPs). Currently DRAMP has been updated to version 2.0, it contains a total of 19,899 entries (newly added 2,550 entries), including 5,084 general entries, 14,739 patent entries, and 76 clinical entries. The update covers new entries, structures, annotations, classifications and downloads. Compared with APD and CAMP, DRAMP contains 14,040 (70.56% in DRAMP) non-overlapping sequences. In order to facilitate users to trace original references, PubMed_ID of references have been contained in activity information. The data of DRAMP can be downloaded by dataset and activity, and the website source code is also available on dedicatedly designed download webpage. Although thousands of AMPs have been reported, only a few parts have entered clinical stage. In the paper, we described several AMPs in clinical trials, including their properties, indications and clinicaltrials.gov identifiers. Finally, we provide the applications of DRAMP in the development of AMPs.

Involvement of Endothelin-1, H2S and Nrf2 in Beneficial Effects of Remote Ischemic Preconditioning in Global Cerebral Ischemia-Induced Vascular Dementia in Mice.

The present study explored the role of endothelin-1, H2S, and Nrf2 in remote preconditioning (RIPC)-induced beneficial effects in ischemia-reperfusion (I/R)-induced vascular dementia. Mice were subjected to 20 min of global ischemia by occluding both carotid arteries to develop vascular dementia, which was assessed using Morris water maze test on 7th day. RIPC was given by subjecting hind limb to four cycles of ischemia (5 min) and reperfusion (5 min) and it significantly restored I/R-induced locomotor impairment, neurological severity score, cerebral infarction, apoptosis markers along with deficits in learning and memory. Biochemically, there was increase in the plasma levels of endothelin-1 along with increase in the brain levels of H2S and its biosynthetic enzymes viz., cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CLS). There was also an increase in the expression of Nrf2 and glutathione reductase in the brain in response to RIPC. Pretreatment with bosentan (dual blocker of ETA and ETB receptors), amino-oxyacetic acid (CBS synthase inhibitor), and DL-propargylglycine (CLS inhibitor) significantly attenuated RIPC-mediated beneficial effects and biochemical alterations. The effects of bosentan on behavioral and biochemical parameters were more significant than individual treatments with CBS or CLS inhibitors. Moreover, CBS and CLS inhibitors did not alter the endothelin-1 levels possibly suggesting that endothelin-1 may act as upstream mediator of H2S. It is concluded that RIPC may stimulate the release endothelin-1, which may activate CBS and CLS to increase the levels of H2S and latter may increase the expression of Nrf2 to decrease oxidative stress and prevent vascular dementia.

Role of hydrogen sulfide in cognitive deficits: Evidences and mechanisms.

Hydrogen sulfide (H2S) is a gaseous molecule and is endogenously produced in the brain by cystathionine beta-synthase, 3-mercaptopyruvate-sulfurtransferase, cysteine aminotransferase and cystathionine γ-lyase. Physiologically, H2S acts as a neuromodulator and regulates synaptic activity of neurons and glia to promote the development of long-term potentiation. A decrease in H2S levels in the brain and plasma has been directly correlated with the degree of severity of Alzheimer disease in patients. A large number of studies have shown a decrease in the H2S levels in experimental models of cognitive dysfunction and exogenous administration of sodium hydrosulfide (NaHS), a H2S donor, has been shown to prevent the development of memory deficits. The beneficial effects of H2S in different models has been ascribed to decrease in neuroinflammation, up-regulation of antioxidant defense, decrease in endoplasmic reticulum (ER) stress, inhibition of phosphatidylinositol 3-kinase (PI3-K)/Akt signaling, inhibition of mitogen activated protein (MAP) kinases, decrease in glutamate and normalization of NMDA receptors, inhibition of matrix metalloproteinases (MMPs), up-regulation of silent information regulator 1 (Sirt 1) and preservation of mitochondrial function. The present review describes the role of H2S in different models of cognitive deficits and human subjects along with possible mechanisms.

Admissibility of simultaneous prediction for actual and average values in finite population.

This paper studies the admissibility of simultaneous prediction of actual and average values of the regressand in the generalized linear regression model under the quadratic loss function. Necessary and sufficient conditions are derived for the simultaneous prediction to be admissible in classes of homogeneous and nonhomogeneous linear predictors, respectively.

The global impact of the DRACMA guidelines cow's milk allergy clinical practice.

BACKGROUND: The 2010 Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow's milk allergy (CMA). They indicate oral food challenge (OFC) as the reference test for diagnosis, and suggest the choice of specific alternative formula in different clinical conditions. Their recommendations are flexible, both in diagnosis and in treatment. OBJECTIVES & METHODS: Using the Scopus citation records, we evaluated the influence of the DRACMA guidelines on milk allergy literature. We also reviewed their impact on successive food allergy and CMA guidelines at national and international level. We describe some economic consequences of their application. RESULTS: DRACMA are the most cited CMA guidelines, and the second cited guidelines on food allergy. Many subsequent guidelines took stock of DRACMA's metanalyses adapting recommendations to the local context. Some of these chose not to consider OFC as an absolute requirement for the diagnosis of CMA. Studies on their implementation show that in this case, the treatment costs may increase and there is a risk of overdiagnosis. Interestingly, we observed a reduction in the cost of alternative formulas following the publication of the DRACMA guidelines. CONCLUSIONS: DRACMA reconciled international differences in the diagnosis and management of CMA. They promoted a cultural debate, improved clinician's knowledge of CMA, improved the quality of diagnosis and care, reduced inappropriate practices, fostered the efficient use of resources, empowered patients, and influenced some public policies. The accruing evidence on diagnosis and treatment of CMA necessitates their update in the near future.

Intrauterine sensitization of ovalbumin in the third trimester increases the risk of food allergy in progeny.

Intrauterine sensitization caused by food allergens plays an important role in the food allergy development in progeny. The aim of our study was to determine the critical period of intrauterine sensitization during pregnancy. Female mice were exposed to ovalbumin (OVA) during different trimesters of pregnancy. Lymphocytes from their offspring were isolated and cultured, and proliferation was evaluated by CCK-8 assay. The levels of IFN-γ and IL-4 in serum were measured using ELISA. In addition, the expressions of IFN-γ and IL-4 mRNAs and proteins were detected by real-time PCR and western blot. The mice were divided into the first trimester pregnancy (FTP1 and FTP2) group, the second trimester pregnancy (STP1 and STP2) group, and the third trimester pregnancy (TTP1 and TTP2) group based on the stages of pregnancy in which their mothers were exposed to OVA and their ages. The OVA-specific lymphocyte proliferation of the TTP1 group was statistically significantly greater that in the FTP1 and STP1 groups. The serum level of IFN-γ in the TTP1 group was significantly decreased, and the serum level of IL-4 in the TTP1 group was significantly increased compared with the levels in the FTP1 and STP1 groups. The mRNA and protein expression levels of IFN-γ in the TTP1 group were significantly decreased and the mRNA and protein expression levels of IL-4 in this group were significantly increased compared with the levels in the FTP1 and STP1 groups. Our results suggest that OVA-induced intrauterine sensitization in the third trimester may increase the risk of food allergy after birth.

World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Vitamin D.

BACKGROUND: The prevalence of allergic diseases is approximately 10 % in infants whose parents and siblings do not have allergic diseases and 20-30 % in those with an allergic first-degree relative. Vitamin D is involved in the regulation of the immune system and it may play a role in the development, severity and course of asthma and other allergic diseases. OBJECTIVE: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations addressing the use of vitamin D in primary prevention of allergic diseases. METHODS: Our WAO guideline panel identified the most relevant clinical questions and performed a systematic review of randomized controlled trials and non-randomized studies (NRS), specifically cohort and case-control studies, of vitamin D supplementation for the prevention of allergic diseases. We also reviewed the evidence about values and preferences, and resource requirements (up to January 2015, with an update on January 30, 2016). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. RESULTS: Having reviewed the currently available evidence, the WAO guideline panel found no support for the hypothesis that vitamin D supplementation reduces the risk of developing allergic diseases in children. The WAO guideline panel suggest not using vitamin D in pregnant women, breastfeeding mothers, or healthy term infants as a means of preventing the development of allergic diseases. This recommendation does not apply to those mothers and infants who have other indications for prophylactic or therapeutic use of vitamin D. The panel's recommendations are conditional and supported by very low certainty evidence. CONCLUSIONS: WAO recommendations about vitamin D supplementation for the prevention of allergic diseases support parents, clinicians and other health care professionals in their decisions whether or not to use vitamin D in preventing allergic diseases in healthy, term infants.

World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics.

BACKGROUND: The prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10 % and reaches 20-30 % in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Prebiotics - non-digestible oligosaccharides that stimulate growth of probiotic bacteria - have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention. OBJECTIVE: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of prebiotics in the prevention of allergy. METHODS: The WAO guideline panel identified the most relevant clinical questions about the use of prebiotics for the prevention of allergy. We performed a systematic review of randomized controlled trials of prebiotics, and reviewed the evidence about patient values and preferences, and resource requirements (up to January 2015, with an update on July 29, 2015). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. RESULTS: Based on GRADE evidence to decision frameworks, the WAO guideline panel suggests using prebiotic supplementation in not-exclusively breastfed infants and not using prebiotic supplementation in exclusively breastfed infants. Both recommendations are conditional and based on very low certainty of the evidence. We found no experimental or observational study of prebiotic supplementation in pregnant women or in breastfeeding mothers. Thus, the WAO guideline panel chose not to provide a recommendation about prebiotic supplementation in pregnancy or during breastfeeding, at this time. CONCLUSIONS: WAO recommendations about prebiotic supplementation for the prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether or not to use prebiotics for the purpose of preventing allergies in healthy, term infants.