Occupational asbestos exposure and ovarian cancer: updated systematic review.

BACKGROUND: The association between asbestos exposure and ovarian cancer has been questioned given the possible misdiagnosis of peritoneal mesothelioma as ovarian cancer. AIMS: To update a systematic review on ovarian cancer risk in women occupationally exposed to asbestos, exploring the association with the time since first exposure and the duration of exposure. METHODS: We searched PubMed from 2008 onwards, screened previous systematic reviews, combined standardized mortality ratios (SMR) using random effect models and quantified heterogeneity using the I2 statistic. To assess tumour misclassification, we compared the distribution of observed excess ovarian cancers (OEOC) to that expected (EEOC) from the distribution of peritoneal cancers in strata of latency and exposure duration. RESULTS: Eighteen publications (20 populations), including a pooled analysis of 21 cohorts, were included. The pooled SMR was 1.79 (95% confidence interval 1.38-2.31), with moderate heterogeneity between studies (I2 = 42%), based on 144 ovarian cancer deaths/cases. The risk was increased for women with indirect indicators of higher exposure, longer duration and latency, and lower for chrysotile than for crocidolite exposure. The effect of duration and latency could not be completely disentangled, since no multivariate analysis was available for time-related variables. The dissimilarity index between OEOC and EEOC for the time since first exposure was small suggesting a similar pattern of risk. CONCLUSIONS: While some misclassification between ovarian and peritoneal cancers cannot be excluded, the observed excess risk of ovarian cancer should be added to the overall disease burden of asbestos.

Evaluating an adapted reverse categorisation task to assess cognitive flexibility in young children with Down syndrome.

BACKGROUND: Accurate measurement of cognitive skills is necessary to advance both developmental and intervention science for individuals with Down syndrome (DS). This study evaluated the feasibility, developmental sensitivity and preliminary reliability of a reverse categorisation measure designed to assess cognitive flexibility in young children with DS. METHODS: Seventy-two children with DS ages 2.5-8 years completed an adapted version of a reverse categorisation task. Twenty-eight of the participants were assessed again 2 weeks later for retest reliability. RESULTS: This adapted measure demonstrated adequate feasibility and developmental sensitivity, and preliminary evidence for test-retest reliability when administered to children with DS in this age range. CONCLUSIONS: This adapted reverse categorisation measure may be useful for future developmental and treatment studies that target early foundations of cognitive flexibility in young children with DS. Additional recommendations for use of this measure are discussed.

Theranostic efficiency of biosurfactants against COVID-19 and similar viruses - A review.

The world has witnessed an extreme vulnerability of a pandemic during 2020; originated from China. The coronavirus disease 2019 (COVID-19) is infecting and beginning deaths in thousands to millions, creating of the global economic crisis. Biosurfactants (BSs) can carry the prevention, control and management of pandemic out through diverse approaches, such as pharmaceutical, therapeutic, hygienic and environmental. The microbiotas having virulent intrinsic properties towards starting as easily as spreading of diseases (huge morbidity and mortality) could be inhibited via BSs. Such elements could be recognised for their antimicrobial activity, capability to interact with the immune system via micelles formation and in nanoparticulate synthesis. However, they can be used for developing novel and more effective therapeutics, pharmaceuticals, non-toxic formulations, vaccines, and effective cleaning agents. Such approaches can be utilized for product development and implemented for managing and combating the pandemic conditions. This review emphasized on the potentiality of BSs as key components with several ways for protecting against unknown and known pathogens, including COVID-19.

PET/MR Imaging in Evaluating Treatment Failure of Head and Neck Malignancies: A Neck Imaging Reporting and Data System-Based Study.

BACKGROUND AND PURPOSE: PET/MR imaging is a relatively new hybrid technology that holds great promise for the evaluation of head and neck cancer. The aim of this study was to assess the performance of simultaneous PET/MR imaging versus MR imaging in the evaluation of posttreatment head and neck malignancies, as determined by its ability to predict locoregional recurrence or progression after imaging. MATERIALS AND METHODS: The electronic medical records of patients who had posttreatment PET/MR imaging studies were reviewed, and after applying the exclusion criteria, we retrospectively included 46 studies. PET/MR imaging studies were independently reviewed by 2 neuroradiologists, who recorded scores based on the Neck Imaging Reporting and Data System (using CT/PET-CT criteria) for the diagnostic MR imaging sequences alone and the combined PET/MR imaging. Treatment failure was determined with either biopsy pathology or initiation of new treatment. Statistical analyses including univariate association, interobserver agreement, and receiver operating characteristic analysis were performed. RESULTS: There was substantial interreader agreement among PET/MR imaging scores (κ = 0.634; 95% CI, 0.605-0.663). PET/MR imaging scores showed a strong association with treatment failure by univariate association analysis, with P < .001 for the primary site, neck lymph nodes, and combined sites. Receiver operating characteristic curves of PET/MR imaging scores versus treatment failure indicated statistically significant diagnostic accuracy (area under curve range, 0.864-0.987; P < .001). CONCLUSIONS: Simultaneous PET/MR imaging has excellent discriminatory performance for treatment outcomes of head and neck malignancy when the Neck Imaging Reporting and Data System is applied. PET/MR imaging could play an important role in surveillance imaging for head and neck cancer.

Latent profiles of autism symptoms in children and adolescents with Down syndrome.

BACKGROUND: Down syndrome (DS) is associated with elevated rates of autism spectrum disorder (ASD) and autism symptomatology. To better characterise heterogeneity in ASD symptomatology in DS, profiles of caregiver-reported ASD symptoms were modelled for children and adolescents with DS. METHODS: Participants (n = 125) were recruited through several multi-site research studies on cognition and language in DS. Using the Social Responsiveness Scale-2 (SRS-2; Constantino and Gruber 2012), two latent profile analyses (LPA) were performed, one on the broad composite scores of social communication and interaction and restricted interests and repetitive behaviour, and a second on the four social dimensions of social communication, social motivation, social awareness, and social cognition. RESULTS: A three-profile model was the best fit for both analyses, with each analysis yielding a low ASD symptom profile, an elevated or mixed ASD symptom profile and a high ASD symptom profile. Associations were observed between profile probability scores and IQ, the number of co-occurring biomedical conditions reported, sex, and SRS-2 form. CONCLUSIONS: Characterising heterogeneity in ASD symptom profiles can inform more personalised supports in this population, and implications for potential therapeutic approaches for individuals with DS are discussed.

Diagnosis, prevention, and treatment of coronavirus disease: a review.

INTRODUCTION: Coronavirus disease (COVID-19) was first reported in Wuhan, China, in late December 2019 and subsequently, declared a pandemic. As of 3 June 2021, 172,493,290 individuals have acquired COVID-19 and 3,708,334 patients have died worldwide, according to the World Health Organization. AREAS COVERED: This review explores epidemiology; virology; pathogenesis; genomic variations; mode of transmission; clinical occurrence; diagnosis; and treatment with antiviral agents, antibiotics, and supportive therapies. It covers a nanotechnology-based treatment approach and emphasizes the importance of herbal and marine antiviral drugs. The review attempts to explain current advances in research, prevention, and control of COVID-19 spread through artificial intelligence and vaccine development status under cosmopolitan consideration. EXPERT OPINION: While COVID-19 research is advancing at full capacity, the discovery of drugs or vaccines that can fight the pandemic is necessary. Human survival in such a critical situation will be possible only with the development of strong immunity by opting for exercise, yoga, and consumption of hygienic food and beverages. Therefore, education about COVID-19 lethality and its impact on livelihood is important. The pandemic has also shown positive effects on the environment, such as a significant reduction in environmental pollution and global warming and improvement in river water quality.

Feasibility of a syndrome-informed micro-intervention for infants with Down syndrome.

BACKGROUND: Infants with Down syndrome (DS) are at risk for a range of phenotypic outcomes, including delays in the onset of reaching behaviour, a critical skill that facilitates early learning. This parallel-group feasibility and pilot study presents findings from a parent-mediated micro-intervention that aimed to support the development of reaching behaviour in a sample of infants with DS. METHODS: Participants were 73 infants with DS and their caregivers. Infants who qualified for the home-based intervention (based on manual skill performance on Bayley Scales of Infant and Toddler Development, Third Edition items) were randomly assigned individually or by geographical region to a treatment or an alternative treatment condition that involved toy-based interactions with caregivers. Infants in the treatment condition experienced facilitated reaching during the toy-based interactions through the use of Velcro-affixed mittens and toys. RESULTS: Forty-two infants met criteria to participate in the intervention, and 37 participated in both baseline and post-treatment visits. At post-treatment, infants in the treatment condition demonstrated shorter latencies to make contact with objects and showed higher frequencies of reach attempts and swats at objects than infants in the alternative treatment group. These findings were more pronounced when examining a chronological age-restricted subgroup of infants 5 to 10 months. CONCLUSIONS: Findings suggest that a syndrome-informed approach to targeted intervention may be a promising application of phenotyping science in DS and other neurogenetic conditions associated with intellectual disability.

Acute metronidazole-induced neurotoxicity: an update on MRI findings.

AIM: To describe a series of 10 cases of metronidazole-induced neurotoxicity (MIN) and review the established literature to better define its clinical and imaging findings. MATERIALS AND METHODS: The clinical presentations and magnetic resonance imaging (MRI) images of 10 patients with clinically diagnosed MIN were reviewed retrospectively. A review of an additional 31 cases from prior published case series was performed. RESULTS: The median age of patients from the authors' institutions with MIN was 54 (range 8-84) years. The median cumulative dose of metronidazole received was 64.5 g (range 7.5-1,380 g). Common presenting neurological symptoms were ataxia (n=6) and altered mental status (n=3). All of the patients (n=10) had symmetric T2 hyperintense lesions in the dentate nuclei at presentation. Other involved structures included the midbrain, corpus callosum, pons, medulla, basal ganglia, and supratentorial white matter. True restricted diffusion was seen in the corpus callosum (n=6). Symptoms resolved in all patients except for one. For the patients with available follow up MRI (n=4), the observed lesions resolved. CONCLUSION: MIN affects both adult and paediatric patients. Symptoms typically occur after prolonged exposure to the antibiotic, but can occur at low cumulative doses. Most frequently involved structures are the dentate nucleus, midbrain, and splenium corpus callosum. Restricted diffusion within the corpus callosum is likely due to cytotoxic oedema. Symptoms typically resolve after cessation of metronidazole, and lesions typically resolve on follow-up imaging.

Challenges and opportunities to prevent tuberculosis in people living with HIV in low-income countries.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

Correlates of early cognition in infants with Down syndrome.

BACKGROUND: While delays in cognitive development are detectable during early development in Down syndrome, the neuropsychological and biomedical underpinnings of cognitive skill acquisition in this population remain poorly understood. METHOD: To explore this issue, 38 infants with Down syndrome [mean chronological age = 9.65 months; SD = 3.64] completed the Bayley Scales of Infant Development-III and a set of laboratory tasks that measured sustained attention (duration of visual attention during a 1-min object exploration task), attention shifting (mean latency to shift attention on an alternating object presentation task) and visual short-term memory (dishabituation to a novel object on a change preference task). RESULTS: Latency to shift attention was negatively associated with Bayley Cognitive Scale raw scores, even when controlling for the effects of chronological age, r (33) = -.41, P = .02. In addition, prematurity status was associated with latency to shift attention. CONCLUSIONS: Early attention shifting may be an important factor that facilitates overall cognitive skill acquisition in infants with Down syndrome, and premature birth may be a risk factor for difficulties on this dimension.

Reliability of parent report measures of behaviour in children with Down syndrome.

BACKGROUND: Behavioural problems are common among children with Down syndrome (DS). Tools to detect and evaluate maladaptive behaviours have been developed for typically developing children and have been evaluated for use among children with intellectual and developmental disabilities. However, these measures have not been evaluated for use specifically in children with DS. This psychometric evaluation is important given that some clinically observed behaviours are not addressed in currently available rating scales. The current study evaluates the psychometric properties of the Child Behavior Checklist (CBCL), a commonly used screening tool developed for typically developing children and commonly used with children with intellectual and developmental disabilities. METHODS: The study investigated the psychometric properties of the CBCL among school-aged children with DS, including an assessment of the rate of detecting behaviour problems, concerns with distribution, internal consistency, inter-rater reliability and convergent and discriminant validity with the Aberrant Behavior Checklist and Nisonger Child Behavior Rating Form. Caregivers of 88 children with DS aged 6-18 years rated their child's behaviour with the CBCL, Aberrant Behavior Checklist and Nisonger Child Behavior Rating Form. Teachers completed the Teacher Report Form. RESULTS: About one-third of children with DS were reported to exhibit behaviours of clinical concern on the total score of the CBCL. Internal consistency for CBCL sub-scales was poor to excellent, and inter-rater reliability was generally acceptable. The sub-scales of the CBCL performed best when evaluating convergent validity, with variable discriminant validity. Normative data conversions controlled for age and gender differences in this sample. CONCLUSIONS: The study findings suggest that, among children with DS, some CBCL sub-scales generally performed in a psychometrically sound and theoretically appropriate manner in relation to other measures of behaviour. Caution is warranted when interpreting specific sub-scales (Anxious/Depressed, Somatic Complaints and Thought Problems). The CBCL can continue to be used as a screening measure when evaluating behavioural concerns among children with DS, acknowledging poor discriminant validity and the possibility that key behaviour concerns in DS may not be captured by the CBCL screen.

Extracting Aggregation Free Energies of Mixed Clusters from Simulations of Small Systems: Application to Ionic Surfactant Micelles.

Micelle cluster distributions from molecular dynamics simulations of a solvent-free coarse-grained model of sodium octyl sulfate (SOS) were analyzed using an improved method to extract equilibrium association constants from small-system simulations containing one or two micelle clusters at equilibrium with free surfactants and counterions. The statistical-thermodynamic and mathematical foundations of this partition-enabled analysis of cluster histograms (PEACH) approach are presented. A dramatic reduction in computational time for analysis was achieved through a strategy similar to the selector variable method to circumvent the need for exhaustive enumeration of the possible partitions of surfactants and counterions into clusters. Using statistics from a set of small-system (up to 60 SOS molecules) simulations as input, equilibrium association constants for micelle clusters were obtained as a function of both number of surfactants and number of associated counterions through a global fitting procedure. The resulting free energies were able to accurately predict micelle size and charge distributions in a large (560 molecule) system. The evolution of micelle size and charge with SOS concentration as predicted by the PEACH-derived free energies and by a phenomenological four-parameter model fit, along with the sensitivity of these predictions to variations in cluster definitions, are analyzed and discussed.

The impact of ionic liquids on the coordination of anions with solvatochromic copper complexes.

Solvatochromic transition metal (TM)-complexes with weakly associating counter-anions are often used to evaluate traditional neutral solvent and anion coordination ability. However, when employed in ionic liquids (IL) many of the common assumptions made are no longer reliable. This study investigates the coordinating ability of weakly coordinating IL anions in traditional solvents and within IL solvents employing a range of solvatochromic copper complexes. Complexes of the form [Cu(acac)(tmen)][X] (acac = acetylacetonate, tmen = tetramethylethylenediamine) where [X]- = [ClO4]-, Cl-, [NO3]-, [SCN]-, [OTf]-, [NTf2]- and [PF6]- have been synthesised and characterised both experimentally and computationally. ILs based on these anions and imidazolium and pyrrolidinium cations, some of which are functionalised with hydroxyl and nitrile groups, have been examined. IL-anion coordination has been investigated and compared to typical weakly coordinating anions. We have found there is potential for competition at the Cu-centre and cases of anions traditionally assigned as weakly associating that demonstrate a stronger than expected level of coordinating ability within ILs. [Cu(acac)(tmen)][PF6] is shown to contain the least coordinating anion and is established as the most sensitive probe studied here. Using this probe, the donor numbers (DNs) of ILs have been determined. Relative donor ability is further confirmed based on the UV-Vis of a neutral complex, [Cu(sacsac)2] (sacsac = dithioacetylacetone), and DNs evaluated via23Na NMR spectroscopy. We demonstrate that ILs can span a wide donor range, similar in breadth to conventional solvents.

Integration of childhood TB into guidelines for the management of acute malnutrition in high burden countries.

Introduction: Childhood tuberculosis (TB) and undernutrition are major global public health challenges. In 2015, although an estimated 1 million children aged <15 years developed TB, the majority of the cases remain undiagnosed, partly due to a lack of awareness and capacity by providers who serve as the first point of care for sick children. This calls for better integration of TB with child health and nutrition services. TB can cause or worsen undernutrition, and undernutrition increases the risk of TB. Methods: Guidelines for the management of acute malnutrition from 17 high TB burden countries were reviewed to gather information on TB symptom screening, exposure history, and treatment. Results: Seven (41%) countries recommend routine TB screening among children with acute malnutrition, and six (35%) recommend obtaining a TB exposure history. Conclusion: TB screening is not consistently included in guidelines for acute malnutrition in high TB burden countries. Routine TB risk assessment, especially history of TB exposure, among acutely malnourished children, combined with improved linkages with TB services, would help increase TB case finding and could impact outcomes. Operational research on how best to integrate services at different levels of the health care system is needed.

Cadre: La tuberculose (TB) de l'enfance et la malnutrition sont des défis majeurs de santé publique dans le monde. On estime qu'un million d'enfants âgés de <15 ans ont eu une TB en 2015, mais la majorité des cas sont restés non diagnostiqués, en partie à cause du manque de connaissance et de capacité des prestataires de soins qui sont le premier point de contact pour les enfants malades ; ceci demande une meilleure intégration de la TB avec les services de santé de l'enfant et de nutrition. La TB peut causer ou aggraver la malnutrition et la malnutrition augmente le risque de TB.Methodes: Les directives pour la prise en charge de la malnutrition aiguë de 17 pays durement frappés par la TB ont été revues afin de rassembler des informations relatives au dépistage des symptômes de TB, des antécédents d'exposition et de traitement.Résultats: Sept (41%) pays recommandent un dépistage de routine de la TB parmi les enfants ayant une malnutrition aiguë et six (35%) recommandent de rechercher des antécédents d'exposition à la TB.Conclusion: Le dépistage de la TB n'est pas systématiquement inclus dans les directives relatives à la malnutrition aiguë dans les pays durement frappés par la TB. Une évaluation de routine du risque de TB, particulièrement des antécédents d'exposition à la TB, parmi les enfants atteints de malnutrition aiguë, combinée à de meilleurs liens avec les services de TB contribuerait à augmenter la découverte des cas de TB et améliorer leur évolution. Une recherche opérationnelle sur la meilleure façon d'intégrer les services à différents niveaux du système de santé est nécessaire.

Marco de referencia: La tuberculosis (TB) durante la infancia y la desnutrición representan graves problemas de salud pública en el mundo. Se estima que un millón de niños de edad de <15 años contrajeron la TB en el 2015, pero la mayoría de los casos permaneció sin diagnóstico, debido en parte a la falta de sensibilización y a la escasa capacidad de los profesionales de salud que atienden en primera línea a los niños enfermos; esta situación exige una mejor integración de los servicios de atención de la TB y los servicios que se ocupan de la salud y la nutrición de los niños. La TB puede causar o agravar la desnutrición y esta a su vez aumenta el riesgo de contraer la TB.Métodos: Se analizaron las directrices de manejo de la desnutrición aguda de 17 países con alta carga de morbilidad por TB, con el objeto de reunir información sobre la detección sistemática de los síntomas, los antecedentes de exposición y el tratamiento de la TB.Resultados: Siete países recomendaban la detección sistemática de la TB en la práctica corriente en los niños con desnutrición aguda (41%) y seis países recomendaban obtener los antecedentes de exposición a la enfermedad (35%).Conclusión: La recomendación de la detección sistemática de la TB no es constante en las directrices de manejo de la desnutrición en los países con alta carga de morbilidad por esta enfermedad. La práctica corriente de una evaluación del riesgo de TB, sobre todo de los antecedentes de exposición en los niños aquejados de desnutrición aguda, aunada a mejores vínculos con los servicios de atención de la TB contribuiría a aumentar el rendimiento de la búsqueda de casos y mejorar los desenlaces. Sería muy útil realizar investigaciones operativas sobre la mejor manera de integrar los servicios en los diferentes niveles del sistema de atención de salud.

Successful Implementation of Clinical Information Technology: Seven Key Lessons from CPOE.

OBJECTIVES: To identify and describe the most critical strategic and operational contributors to the successful implementation of clinical information technologies, as deployed within a moderate sized system of U.S. community hospitals. BACKGROUND AND SETTING: CHRISTUS Health is a multi-state system comprised of more than 350 services and 60 hospitals with over 9 000 physicians. The Santa Rosa region of CHRISTUS Health, located in greater San Antonio, Texas is comprised of three adult community hospital facilities and one Children's hospital each with bed capacities of 142-180. Computerized Patient Order Entry (CPOE) was first implemented in 2012 within a complex market environment. The Santa Rosa region has 2 417 credentialed physicians and 263 mid-level allied health professionals. METHODS: This report focuses on the seven most valuable strategies deployed by the Health Informatics team in a large four hospital CHRISTUS region to achieve strong CPOE adoption and critical success lessons learned. The findings are placed within the context of the literature describing best practices in health information technology implementation. RESULTS: While the elements described involved discrete de novo process generation to support implementation and operations, collectively they represent the creation of a new customer-centric service culture in our Health Informatics team, which has served as a foundation for ensuring strong clinical information technology adoption beyond CPOE. CONCLUSION: The seven success factors described are not limited in their value to and impact on CPOE adoption, but generalize to - and can advance success in - varied other clinical information technology implementations across diverse hospitals. A number of these factors are supported by reports in the literature of other institutions' successful implementations of CPOE and other clinical information technologies, and while not prescriptive to other settings, may be adapted to yield value elsewhere.

Formulation of fenofibrate liquisolid tablets using central composite design.

Liquisolid technique has been widely used to enhance the dissolution of poorly water soluble drugs. The present investigation is on formulation of liquisolid tablets of fenofibrate, a lipid lowering agent. Liquisolid formulation was prepared by applying central composite design (CCD) to optimize various formulation parameters. Amounts of PEG 600 (X1), Avicel PH 102 (X2), and Aerosil 200 (X3) were selected as independent variables while the angle of repose, hardness, disintegration time, and T90% (time required to release 90% drug) of liquisolid tablets were selected as dependent variables. Optimization of formulation was done by multiple linear regression analysis. The results indicated amounts of PEG 600 and Aviel PH 102 show greater effect on dependant variables. In vitro dissolution of fenofibrate in liquisolid formulations was enhanced compared to the pure form. To conclude, Liquisolid technique is a promising strategy in improving dissolution of poorly water soluble fenofibrate.

Insights into the pathophysiology of catch-up compared with non-catch-up growth in children born small for gestational age: an integrated analysis of metabolic and transcriptomic data.

Small for gestational age (SGA) children exhibiting catch-up (CU) growth have a greater risk of cardiometabolic diseases in later life compared with non-catch-up (NCU) SGA children. The aim of this study was to establish differences in metabolism and gene expression profiles between CU and NCU at age 4-9 years. CU children (n=22) had greater height, weight and body mass index standard deviation scores along with insulin-like growth factor-I (IGF-I) and fasting glucose levels but lower adiponectin values than NCU children (n=11; all P<0.05). Metabolic profiling demonstrated a fourfold decrease of urine myo-inositol in CU compared with NCU (P<0.05). There were 1558 genes differentially expressed in peripheral blood mononuclear cells between the groups (P<0.05). Integrated analysis of data identified myo-inositol related to gene clusters associated with an increase in insulin, growth factor and IGF-I signalling in CU children (P<0.05). Metabolic and transcriptomic profiles in CU SGA children showed changes that may relate to cardiometabolic risk.

The contribution of rapid KATP channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism.

OBJECTIVE: In children with congenital hyperinsulinism (CHI), K(ATP) channel genes (ABCC8 and KCNJ11) can be screened rapidly for potential pathogenic mutations. We aimed to assess the contribution of rapid genetic testing to the clinical management of CHI. DESIGN: Follow-up observational study at two CHI referral hospitals. METHODS: Clinical outcomes such as subtotal pancreatectomy, (18)F-Dopa positron emission tomography-computed tomography (PET-CT) scanning, stability on medical treatment and remission were assessed in a cohort of 101 children with CHI. RESULTS: In total, 32 (32%) children had pathogenic mutations in K(ATP) channel genes (27 in ABCC8 and five in KCNJ11), of which 11 (34%) were novel. In those negative at initial screening, other mutations (GLUD1, GCK, and HNF4A) were identified in three children. Those with homozygous/compound heterozygous ABCC8/KCNJ11 mutations were more likely to require a subtotal pancreatectomy CHI (7/10, 70%). Those with paternal heterozygous mutations were investigated with (18)F-Dopa PET-CT scanning and 7/13 (54%) had a focal lesionectomy, whereas four (31%) required subtotal pancreatectomy for diffuse CHI. Those with maternal heterozygous mutations were most likely to achieve remission (5/5, 100%). In 66 with no identified mutation, 43 (65%) achieved remission, 22 (33%) were stable on medical treatment and only one child required a subtotal pancreatectomy. CONCLUSIONS: Rapid genetic analysis is important in the management pathway of CHI; it provides aetiological confirmation of the diagnosis, indicates the likely need for a subtotal pancreatectomy and identifies those who require (18)F-Dopa PET-CT scanning. In the absence of a mutation, reassurance of a favourable outcome can be given early in the course of CHI.

Design and Development of Thermoreversible Ophthalmic In Situ Hydrogel of Moxifloxacin HCl.

Conventional eye drops show relatively low bioavailability due to poor precorneal contact time. In situ hydrogels are of great importance in providing sustained ocular drug delivery. By exhibiting elastic properties they resist ocular drainage of the drug leading to longer contact times. In the present study an in situ gelling thermoreversible mucoadhesive gel was formulated of an antibacterial agent, Moxifloxacin HCl using a combination of poloxamer 407 and poloxamer 188 with different mucoadhesive polymers such as Xanthan gum and Sodium alginate with a view to increase gel strength and bioadhesion force and thereby increased precorneal contact time and bioavailability of the drug. Formulations were evaluated for physical parameters like clarity, pH, spreadability, drug content, gelation temperature, gel strength, bioadhesion force and in vitro drug release study. Formulations were found transparent, uniform in consistency and had good spreadability within a pH range of 6.8 to 7.4. A satisfactory bioadhesion (3298 to 4130 Dyne/cm2) on the sheeps corneal surface and good gel strength (95 to 128 sec) was also observed. As the concentration of mucoadhesive polymers in the gel formulation increased, the rate of drug release decreased. The order of drug release was in order: Xanthan gum > Sodium alginate. It was concluded that a thermoreversible in situ gel of Moxifloxacin HCl can be formulated by combining with mucoadhesive polymers and used effectively as safe and sustained ocular drug delivery. This combination provided greater bioadhesion force and gel strength as compared to the thermoreversible polymers i.e., poloxamer 407 (PF 127) or 188 (PF 68) when used alone.

Studies on Poloxamer Based Mucoadhesive Insitu Ophthalmic Hydrogel of Moxifloxacin HCL.

Conventional eye drops shows relatively low bioavailability due to poor precorneal contact time. In situ hydrogels are of great importance in providing sustained ocular drug delivery due to their elastic properties hydrogels resist ocular drainage leading to longer contact times. In the present study an in situ gelling thermoreversible mucoadhesive gel was formulated of an antibacterial agent Moxifloxacin HCl using combination of poloxamer 407 and poloxamer 188 with different mucoadhesive polymers such as Xanthan gum and Sodium alginate with a view to increase in gel strength and bioadhesion force and thereby increase in precorneal contact time and there by increase in bioavailability of the drug. The formulations were evaluated for physical parameters like Clarity, pH, spreadability, drug content, gelation temperature, gel strength, bioadhesion force and in vitro drug release study. The formulated gels were transparent, uniform in consistency and had spreadability with a pH range of 6.8 to 7.4. A satisfactory bioadhesion (3298 to 4130 Dyne/cm(2)) on the sheep's corneal surface and good gel strength (95 to 128 sec) were also observed. As the concentration of mucoadhesive polymers in the gel formulation increases, the rate of drug release decreases. The order of drug release was Xanthan gum>Sodium alginate. It was concluded that a thermoreversible in situ gel formulation with Moxifloxacin HCl can be formulated by combining with mucoadhesive polymers and can effectively be used in safe and sustained ocular drug delivery with greater bioadhesion force and gel strength as compared to the thermoreversible polymers poloxamer 407 or 188 when used alone.