Clinical profile of functional constipation in Saudi children.

BACKGROUND: Functional constipation (FC) is a common condition in children, and information on the clinical characteristics of FC in Saudi children is scarce. OBJECTIVE: Describe the clinical profile of FC in Saudi children. DESIGN: Retrospective. SETTING: Hospital that provides primary, intermediate and tertiary care. PATIENTS AND METHODS: All children diagnosed with FC according to the Rome IV criteria were included and had at least one follow-up clinic visit. Demographic and clinical data collected from medical records included the age at onset, duration of constipation, clinical features, treatment modalities, and factors associated with clinical response. Descriptive statistics and Pearson's chi-squared test were used in the statistical analysis to see how categorical study variables were linked to clinical response. A P value of ≤.05 was used to report statistical significance. MAIN OUTCOME MEASURE: Compliance and clinical response to polyethylene glycol (PEG) compared with lactulose. SAMPLE SIZE: 370 children from 0.1 to 13 years of age. RESULTS: The median (IQR) age of onset was 4 (5) years and less than one year in 14%. The median (IQR) duration of constipation was 4 months (11) and less than two months in 93/370 (25%). Abdominal pain was the most commonly associated feature (44%). Screening for celiac disease and hypothyroidism was negative. A Fleet enema was the most common disimpaction method (54%) and PEG was the most common maintenance medication (63.4%). PEG was significantly better tolerated (P=.0008) and more effective than lactulose (P<.0001). Compliance was the only variable significantly associated with clinical response. CONCLUSIONS: PEG was better tolerated and more effective than lactulose in our study, a finding in agreement with the literature. Therefore, PEG should be the drug of choice in the initial management of FC in Saudi children. Prospective studies on the causes of noncompliance are needed to improve the response to treatment. LIMITATIONS: The limitations of retrospective design are missing data, recall bias, and hospital-based limitation, such as missing milder cases treated at the outpatient level. However, the sample size of 370 may have minimized these limitations.

Bushen Formula promotes the decrease of HBsAg levels in patients with CHB by regulating Tfh cells and B-cell subsets.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Formula (BSF) is the effective traditional Chinese medicine (TCM) for chronic hepatitis B (CHB) according to our previous researches. However, the special effectiveness of BSF treating CHB patients in different stages and the immunoregulatory mechanisms remain to be explored. AIM OF THE STUDY: To compare the therapeutic effects of BSF in both treatment-naive patients and Peg-IFN-α-treated patients, and explore the potential mechanism of immunomodulation. MATERIALS AND METHODS: Ultra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry and the TCMSP database were used to determine the main components of BSF. Two hundred and sixty-six patients were enrolled in the retrospective study, and they were divided into the treatment group (T-Group, BSF plus Peg-IFN-α) and the control group (C-Group, Peg-IFN-α monotherapy). Within each group, patients were further grouped into subgroups, namely T1/C1 groups (treatment-naive patients, T1 = 34, C1 = 94) and T2/C2 groups (Peg-IFN-α-treated patients, T2 = 56, C2 = 82). Serum HBV markers, serum HBV DNA levels, serum ALT/AST and TCM symptoms were obtained from the record. Bioinformatics analysis was employed to obtain the potential immunoregulatory mechanisms of BSF treating CHB patients. Among patients in T2 and C2 group, peripheral mononuclear cells from 36 patients were used to analyze the characteristics of peripheral follicular helper T (Tfh) cells and B-cell subtypes by flow cytometry. Preparation of BSF-containing serum in rats. In vitro, the co-culture system of CXCR5+ cells and HepG2.2.15 cells was built to investigate the immunoregulatory effects of BSF. RESULTS: A total of 14 main active compounds were detected in BSF, which were deemed critical for the treatment of CHB. Our findings indicated that the T2-Group exhibited the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the C2-Group (35.7% vs. 15.9%, P = 0.033; 33.9% vs. 11.0%, P = 0.002). Additionally, the T2-Group demonstrated the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the T1-Group (35.7% vs. 14.7%, P = 0.031; 33.9% vs. 2.9%, P = 0.000). The total effective rate based on TCM clinical syndrome in T1-Group and T2-Group were significantly greater than those in C1-Group and C2-Group (85.3% vs. 61.7%, P = 0.012; 89.1% vs. 63.4%, P = 0.000). Bioinformatics analysis indicated that the immunoregulatory mechanisms of BSF treating CHB patients were mainly linked to the growth and stimulation of B-cell, T-cell differentiation, and the signaling pathway of the B-cell receptor. Furthermore, the frequencies of Tfh cells and its IL-21 level, and the IL-21R expressed by B-cell were all increased after BSF treatment. Additionally, in the co-culture system of CXCR5+ cells and HepG2.2.15 cells, HBsAg and HBeAg levels were decreased after BSF-containing serum treatment，as well as the up-regulating of Tfh cell frequencies and down-regulating of B-cell frequencies. CONCLUSIONS: BSF have the higher percentage of HBsAg decline and HBeAg seroclearance in Peg-IFN-α-treated patients compared with treatment-naive patients. The potential immunoregulatory mechanism may correlate with promoting the interaction between Tfh cells and B-cell through IL-21/IL-21R signaling pathway.

Radiologically supervised bowel management program outcome in patients with chronic idiopathic constipation.

PURPOSE: This study aimed to analyze our radiologically supervised bowel management program (RS-BMP) outcomes in patients with chronic idiopathic constipation (CIC). METHODS: A retrospective study was conducted. We included all patients with CIC who participated in our RS-BMP at Children´s Hospital Colorado from July 2016 to October 2022. RESULTS: Eighty patients were included. The average time with constipation was 5.6 years. Before our RS-BMP, 95% had received non-radiologically supervised treatments, and 71% had attempted two or more treatments. Overall, 90% had tried Polyethylene Glycol and 43% Senna. Nine patients had a history of Botox injections. Five underwent anterograde continence procedure, and one a sigmoidectomy. Behavioral disorders (BD) were found in 23%. At the end of the RS-BMP, 96% of patients had successful outcomes, 73% were on Senna, and 27% were on enemas. Megarectum was detected in 93% of patients with successful outcomes and 100% with unsuccessful outcomes (p = 0.210). Of the patients with BD, 89% had successful outcomes, and 11% had unsuccessful. CONCLUSION: Our RS-BMP has been proven to be effective in treating CIC. The radiologically supervised use of Senna and enemas was the appropriate treatment in 96% of the patients. BD and megarectum were associated with unsuccessful outcomes.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

The Safety of Neoadjuvant Therapy with Polyethylene Glycol Liposome Adriamycin Combined with Docetaxel in Patients with Breast Cancer Complicated by Axillary Lymph Node Metastasis.

Objective: To evaluate the safety of the combination of pegylated liposomal doxorubicin and docetaxel in neoadjuvant therapy for breast cancer (BC) with axillary lymph nodes metastasis. Methods: In this single-arm study, 91 patients with clinical stage IIA-IIIc BC received 6 cycles of pegylated liposomal doxorubicin plus docetaxel as neoadjuvant chemotherapy (NAC). Trastuzumab was allowed in patients with human epidermal growth factor receptor 2-positive tumors. The effects of new anthracycline-polyethylene glycol liposomal doxorubicin on the patients' hearts were studied. The changes in left ventricular ejection fraction (LVEF) before and after treatment were evaluated by echocardiography, and the levels of cardiac-specific biomarker troponin I (cTnI) and N terminal B natriuretic peptide (NT-pro-BNP) were noted before and after treatment. Result: In our study, 88 patients completed 6 cycles of neoadjuvant chemotherapy. LVEF was within normal range; average LVEF was 67% at baseline, 66% after NAC. The difference was not statistically significant. However, LVEF decreased by more than 10% in 44.4% of patients. There was no significant difference in troponin I or NT-pro-BNP levels before or after treatment. No cardiac events with clinical symptoms were reported. Conclusion: The combination of polyethylene glycol liposome adriamycin and docetaxel in neoadjuvant chemotherapy in patients with early BC with axillary lymph node metastasis has certain cardiac safety. And in the human epidermal growth factor receptor-2 (HER-2) positive population, polyethylene glycol liposome adriamycin combined with docetaxel and trastuzumab also has certain cardiac safety.

Evaluation of bowel preparation regimens for colonoscopy including a novel low volume regimen (Plenvu): CLEANSE study.

BACKGROUND: Poor bowel preparation is the leading cause of failed colonoscopies and increases costs significantly. Several, split preparation, 2 day regimens are available and recently, Plenvu, a low-volume preparation which can be given on 1 day has been introduced. AIMS: Assess efficacy and tolerability of commonly used purgative regimens including Plenvu. METHOD: In this service evaluation, patients undergoing screening colonoscopy at St Mark's Hospital, London (February 2020-December 2021) were provided Plenvu (1 or 2 days), Moviprep (2 days) or Senna & Citramag (2 days).Boston Bowel Preparation Scale (BBPS) score, fluid volumes and procedure times were recorded. A patient experience questionnaire evaluated taste, volume acceptability, completion and side effects. RESULTS: 563 patients were invited to participate and 553 included: 218 Moviprep 2 days, 108 Senna & Citramag 2 days, 152 Plenvu 2 days and 75 Plenvu 1 day.BBPS scores were higher with Plenvu 1 and 2 days vs Senna & Citramag (p=0.003 and 0.002, respectively) and vs Moviprep (p=0.003 and 0.001, respectively). No other significant pairwise BBPS differences and no difference in preparation adequacy was seen between the groups.Patients rated taste as most pleasant with Senna & Citramag and this achieved significance versus Plenvu 1 day and 2 days (p=0.002 and p<0.001, respectively) and versus Moviprep (p=0.04). CONCLUSION: BBPS score was higher for 1 day and 2 days Plenvu versus both Senna & Citramag and Moviprep. Taste was not highly rated for Plenvu but it appears to offer effective cleansing even when given as a same day preparation.

Abalone-Inspired Adhesive and Photo-Responsive Microparticle Delivery Systems for Periodontal Drug Therapy.

Antibiotics provide promising strategies for treating periodontitis, while their delivery and controllable release with desired oral retention remain challenging. Here, inspired by the unique suction-cup structures of abalones, a novel adhesive and photo-responsive microparticle (MP) delivery system is developed to treat periodontitis through microfluidic electrospray technology. Such MPs are generated by quickly ionic cross-linking of sodium alginate together with photo-curing of poly(ethylene glycol) diacrylate of the distorted microfluidic droplets during their high-speed dropping into calcium chloride solution. Attributing to their unique concave structures, the abalone-inspired MPs exhibit desired underwater adhesion ability and stability under running water. In addition, due to the loading of antibiotics minocycline hydrochloride and near-infrared (NIR)-responsive black phosphorus during their fabrication, the resultant MPs can not only eradicate bacteria directly, but also realize a controllable and effective drug release upon NIR irradiation. Based on these features, it is demonstrated from in vivo periodontitis that the abalone-inspired MPs are firmly adhesive and can controlled-release drugs on the tooth, and thus have outstanding antibacterial efficacy against Porphyromonas gingivalis. These results indicate the particular values of the abalone-inspired MPs for oral-related disease treatment.

Rosa damascena together with brown sugar mitigate functional constipation in children over 12 months old: A double-blind randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa × damascena Herrm., known as damask rose, is a bushy shrub that is found abundantly in Fars province, Iran. This species has been used in Iranian traditional practices for the treatment of abdominal pain and constipation, as gastrointestinal diseases. Brown sugar (Saccharum officinarum L.) has also shown laxative effects in pediatric patients with functional constipation. AIM OF STUDY: This study aimed to compare the effects of Polyethylene Glycol (PEG) and a syrup made of R. damascena and brown sugar on the treatment of functional constipation in children aged above 12 months. MATERIALS AND METHODS: This double-blind randomized clinical trial was performed on 100 patients. One group received PEG and the other received an herbal syrup containing the decocted extract of 0.1 g R. damascena petals mixed with 0.85 g brown sugar per 1 mL. The patients were followed up for two and four weeks and their progresses were recorded. RESULTS: The cure rate was 100% in the R. damascena group and 91.7% in the control group. R. damascena and brown sugar syrup had an odds ratio of 1.09 in the treatment of functional constipation compared to PEG, but the difference was not statistically significant. The only adverse effect detected in the R. damascena group after four weeks was the bad taste of the medication that was too sweet. Nonetheless, this could be solved during the pharmaceutical processes. CONCLUSION: The R. damascena extract and brown sugar syrup can be used as an effective, safe, and inexpensive agent in the treatment of functional constipation.

Folate-Targeted Curcumin-Loaded Niosomes for Site-Specific Delivery in Breast Cancer Treatment: In Silico and In Vitro Study.

As the most common cancer in women, efforts have been made to develop novel nanomedicine-based therapeutics for breast cancer. In the present study, the in silico curcumin (Cur) properties were investigated, and we found some important drawbacks of Cur. To enhance cancer therapeutics of Cur, three different nonionic surfactants (span 20, 60, and 80) were used to prepare various Cur-loaded niosomes (Nio-Cur). Then, fabricated Nio-Cur were decorated with folic acid (FA) and polyethylene glycol (PEG) for breast cancer suppression. For PEG-FA@Nio-Cur, the gene expression levels of Bax and p53 were higher compared to free drug and Nio-Cur. With PEG-FA-decorated Nio-Cur, levels of Bcl2 were lower than the free drug and Nio-Cur. When MCF7 and 4T1 cell uptake tests of PEG-FA@Nio-Cur and Nio-Cur were investigated, the results showed that the PEG-FA-modified niosomes exhibited the most preponderant endocytosis. In vitro experiments demonstrate that PEG-FA@Nio-Cur is a promising strategy for the delivery of Cur in breast cancer therapy. Breast cancer cells absorbed the prepared nanoformulations and exhibited sustained drug release characteristics.

Alantolactone-Loaded Pegylated Prodrug Nanocarriers for Synergistic Treatment of Cisplatin-Resistant Ovarian Cancer via Reactivating Mitochondrial Apoptotic Pathway.

Ovarian cancer (OV) seriously damages women's health because of refractory OV and the development of platinum (Pt) resistance. New treatment strategies are urgently needed to deal with the treatment of cisplatin-resistant OV. Here, a reduction-sensitive pegylated Pt(IV) prodrug was synthesized by amidation of methoxy polyethylene glycol amine (PEG750-NH2) with monocarboxylic Pt(IV) prodrug (Pt(IV)-COOH). Then alantolactone (AL) loaded PEG-Pt(IV) nanocarriers (NP(Pt)@AL) were prepared. In the cisplatin-resistant model of OV, cancer cells actively ingest NP(Pt)@AL through endocytosis, and AL and Pt(II) were disintegrated and released under high intracellular reductant condition. The activity of thioredoxin reductase 1 (TrxR1) inhibited by AL and the adducts of Pt(II) with mitochondrial DNA (mDNA) can costimulate reactive oxygen species (ROS) and reactivate the mitochondrial pathway of apoptosis. Meanwhile, Pt(II) binds with nuclear DNA (nDNA) to jointly promote cell apoptosis. Both in vitro and in vivo results demonstrated that NP(Pt)@AL could effectively reverse the drug resistance and displayed excellent synergistic therapeutic efficacy on platinum-resistant OV with high safety. Therefore, reactivation of the mitochondrial pathway of apoptosis would be a potential strategy to improve the therapeutic effect of Pt-based chemotherapy and even reverse drug resistance.

[Clinical efficacy of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation: a prospective randomized controlled trial]. / 自适应式生物反馈疗法联合口服复方聚乙二醇4000ç”µè§£è´¨æ•£æ²»ç–—å„¿ç«¥å‡ºå£æ¢—é˜»åž‹ä¾¿ç§˜çš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the clinical efficacy, advantages, and disadvantages of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation (OOC). METHODS: A total of 168 children with OOC were enrolled in this prospective study. All the subjects were randomly divided into a test group and a control group based on the order of visiting time, 84 in each group. The test group was treated with adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder, and the control group was treated with oral administration of compound polyethylene glycol 4000-electrolyte powder alone. Eleven children in the test group and two children in the control group withdrew from the study since they could not finish the whole treatment course. Finally, 73 children in the test group and 82 children in the control group were included in this analysis. As clinical outcomes, the total score of clinical symptoms and overall response rate were compared between the two groups at weeks 4 and 8 of treatment. RESULTS: There was no significant difference in the total score of clinical symptoms between the two groups at beginning of treatment and at week 4 (P>0.05), while the test group had a significantly lower total score of clinical symptoms than the control group at week 8 (P<0.05). At week 4, there was no significant difference in overall response rate between the two groups (P>0.05), while the test group had a significantly higher overall response rate than the control group at week 8 (P<0.05). CONCLUSIONS: Adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder is significantly associated with improvement of clinical outcomes in the treatment of children with OOC.

Supramolecular Core-Shell Nanoassemblies with Tumor Microenvironment-Triggered Size and Structure Switch for Improved Photothermal Therapy.

Photothermal therapy (PTT) is demonstrated to be an effective methodology for cancer treatment. However, the relatively low photothermal conversion efficiency, limited tumor accumulation, and penetration still remain to be challenging issues that hinder the clinical application of PTT. Herein, the core-shell hierarchical nanostructures induced by host-guest interaction between water-soluble pillar[5]arene (WP5) and polyethylene glycol-modified aniline tetramer (TAPEG) are constructed. The pH-responsive performance endows the core-shell nanostructures with size switchable property, with an average diameter of 200 nm in the neutral pH and 60 nm in the acidic microenvironment, which facilitates not only tumor accumulation but also tumor penetration. Moreover, the structure switch of WP5⊃TAPEG under acidic microenvironment and the dual mechanism regulated extending of п conjugate, inclusion in the hydrophobic cavity of WP5 and the dense distribution in the core-shell structured assemblies, dramatically enhance the absorption in the near-infrared-II region and, further, the photothermal conversion efficiency (60.2%). The as-designed intelligent nanoplatform is demonstrated for improved antitumor efficacy via PTT.

Biodegradable Ru-Containing Polycarbonate Micelles for Photoinduced Anticancer Multitherapeutic Agent Delivery and Phototherapy Enhancement.

The lack of selectivity between tumor and healthy cells, along with inefficient reactive oxygen species production in solid tumors, are two major impediments to the development of anticancer Ru complexes. The development of photoinduced combination therapy based on biodegradable polymers that can be light activated in the "therapeutic window" would be beneficial for enhancing the therapeutic efficacy of Ru complexes. Herein, a biodegradable Ru-containing polymer (poly(DCARu)) is developed, in which two different therapeutics (the drug and the Ru complex) are rationally integrated and then conjugated to a diblock copolymer (MPEG-b-PMCC) containing hydrophilic poly(ethylene glycol) and cyano-functionalized polycarbonate with good degradability and biocompatibility. The polymer self-assembles into micelles with high drug loading capacity, which can be efficiently internalized into tumor cells. Red light induces the generation of singlet oxygen and the release of anticancer drug-Ru complex conjugates from poly(DCARu) micelles, hence inhibiting tumor cell growth. Furthermore, the phototherapy of polymer micelles demonstrates remarkable inhibition of tumor growth in vivo. Meanwhile, polymer micelles exhibit good biocompatibility with blood and healthy tissues, which opens up opportunities for multitherapeutic agent delivery and enhanced phototherapy.

The magnitude and management of functional constipation at pediatric gastroenterology clinics: A survey study of various countries.

BACKGROUND AND AIM: There have been no large-scale epidemiological study of functional constipation of pediatric gastroenterology services. This survey was undertaken to investigate the prevalence of functional constipation and magnitude of related problems in hospital settings of various countries as well as the practice of pediatric gastroenterologists in management of these conditions. METHODS: The survey was conducted by sending questionnaires to members of Societies for Pediatric Gastroenterology Hepatology and Nutrition of various continents. RESULTS: A total of 274 pediatric gastroenterologists from 41 countries participated in this study. Functional constipation accounted for overall 30% of patients attending pediatric gastroenterology outpatient clinics. In comparison with non-western countries, respondents from western countries reported significantly higher median annual numbers of new patients with intractable functional constipation (10 [4,25] vs 5 [2,10], P < 0.001), dyssynergic defecation (3 [0,15] vs 1 [0,4], P < 0.001), and colonic inertia (2 [0,5] vs 0 [0,1], P < 0.001). The use of high dose polyethylene glycol for fecal disimpaction was significantly more commonly among respondents from western countries, whereas rectal enema was significantly more favored in non-western countries. Respondents from different continents reported significant discrepancies in choices of investigations and management of patients with dyssynergic defecation and colonic inertia. CONCLUSIONS: Functional constipation is a major problem for pediatric gastroenterology outpatient services worldwide. There were significant variations in the investigations of choice and therapeutic management of functional constipation, intractable functional constipation, and related problems among pediatric gastroenterologists of different geographic regions.

Clinical efficacy of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the clinical efficacy, advantages, and disadvantages of adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder in the treatment of children with outlet obstruction constipation (OOC).@*METHODS@#A total of 168 children with OOC were enrolled in this prospective study. All the subjects were randomly divided into a test group and a control group based on the order of visiting time, 84 in each group. The test group was treated with adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder, and the control group was treated with oral administration of compound polyethylene glycol 4000-electrolyte powder alone. Eleven children in the test group and two children in the control group withdrew from the study since they could not finish the whole treatment course. Finally, 73 children in the test group and 82 children in the control group were included in this analysis. As clinical outcomes, the total score of clinical symptoms and overall response rate were compared between the two groups at weeks 4 and 8 of treatment.@*RESULTS@#There was no significant difference in the total score of clinical symptoms between the two groups at beginning of treatment and at week 4 (P>0.05), while the test group had a significantly lower total score of clinical symptoms than the control group at week 8 (P<0.05). At week 4, there was no significant difference in overall response rate between the two groups (P>0.05), while the test group had a significantly higher overall response rate than the control group at week 8 (P<0.05).@*CONCLUSIONS@#Adaptive biofeedback training combined with oral administration of compound polyethylene glycol 4000-electrolyte powder is significantly associated with improvement of clinical outcomes in the treatment of children with OOC.

Block copolymers in Alzheimer's disease therapy: A perceptive to revolutionize biomaterials.

Alzheimer's disease is a fatal illness associated with two persistent problems in treatment i. ineffective drug transportation across the bio-membranes and ii. on-site targeting. Such problems originate from the combinational factors for non-specific targets, physicochemical limitations in the delivery of the active agents and insignificant permeability across blood-brain-barrier. In this context, block copolymers such as PLGA-PEG, PEG-PLA, Poloxamers, PLGA-PEG-PLGA triblock copolymers, etc. present interesting potential in the development of nano-sized carrier systems like polymerosomes, polymeric micelles, etc. for the management and treatment of Alzheimer's disease. Modifications of block copolymers display improvement in solubility and reduction in toxicity due to the process of complexation, functionalization, dose reduction and modification of kinetics for the rate of release. This review article focuses on new insights into different copolymers and their superiority over conventional polymers in Alzheimer's disease for long-term therapy in the body. Association of block copolymers to therapy of Alzheimer's disease overcome the limitations of drug delivery by offering attributes such as smaller molecular size (less than 150 nm), higher solubility owing to hydrophilic interactions between polymeric components and systemic environment, better entrapment efficiency (above 80%) due to large effective surface area and long-term stability for sensitive actives such as peptides, monoclonal antibodies, curcumin, resveratrol, catechins, etc. With such multifunctional features, block copolymers actively permeate the bio-membrane as polymeric nanoparticles, nanomicelles and polymerosomes using different mechanisms such as transcellular- and receptor-mediated transportation to reach target neural network as well as extra-neuronal amyloid-ß plaques for anti-Alzheimer's disease activity with neuroprotective action. These polymers emerge as important components for personalized therapy with potential applications in biosensing, drug delivery, theranostics, etc. for qualitative and quantitative predictions in the detection and treatment of Alzheimer's disease.

Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues.

Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes' pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-ß/collagen, Wnt/ß-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.

Drug development of lyso-thermosensitive liposomal doxorubicin: Combining hyperthermia and thermosensitive drug delivery.

We review the drug development of lyso-thermosensitive liposomal doxorubicin (LTLD) which is the first heat-activated formulation of a liposomal drug carrier to be utilized in human clinical trials. This class of compounds is designed to carry a payload of a cytotoxic agent and adequately circulate in order to accumulate at a tumor that is being heated. At the target the carrier is activated by heat and releases its contents at high concentrations. We summarize the preclinical and clinical experience of LTLD including its successes and challenges in the development process.

Confirmed long-term safety and efficacy of prophylactic treatment with BAY 94-9027 in severe haemophilia A: final results of the PROTECT VIII extension study.

INTRODUCTION: The phase 2/3 PROTECT VIII main study demonstrated efficacy and safety of BAY 94-9027 (damoctocog alfa pegol; Jivi® ), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to extend its half-life. AIM: To report the final efficacy and safety data for BAY 94-9027 from the PROTECT VIII extension. METHODS: Previously treated males aged 12-65 years with severe haemophilia A (FVIII <1%) who completed the multicentre, open-label PROTECT VIII main study were eligible for the extension. Patients received either on demand or prophylaxis treatments (30-40 IU/kg twice weekly [2 × W], 45-60 IU/kg every 5 days [E5D], or 60 IU/kg every 7 days [E7D]) and could switch to any prophylaxis regimen (variable frequency) as needed. Annualised bleeding rates (ABR), zero bleeds and safety outcomes were included in this final analysis. RESULTS: At extension completion, patients (n = 121) received BAY 94-9027 for a median (range) total time of 3.9 (0.8-7.0) years. Median (Q1; Q3) total ABR was 1.49 (0.36; 4.80) for prophylaxis patients (n = 107), compared with 34.09 (20.3; 36.6) for on-demand patients (n = 14). Median total ABRs for 2 × W (n = 23), E5D (n = 33), E7D (n = 23) and variable frequency (n = 28) groups were 1.57, 1.17, 0.65 and 3.10, respectively. Of prophylaxis patients, 20.6% were bleed-free during the entire extension (median time, 3.2 years) and 50.0% were bleed-free during the last 6 months. No patient developed FVIII inhibitors. No deaths or thrombotic events were reported. CONCLUSIONS: Efficacy and safety of BAY 94-9027 was confirmed, with extension data supporting its use as a long-term treatment option for patients with haemophilia A.