The Centers for Disease Control and FITNESSGRAM BMI percentile thresholds are commonly used for obesity screening in youth. It is assumed that these thresholds are predictive of metabolic health risk, but little diagnostic data are available.

Both thresholds are predictive of metabolic syndrome, more so for boys than for girls, although with differing sensitivity and specificity. The diagnostic details of the thresholds can inform clinicians and practitioners about how these standards perform in practice. (Read the full article)

There are misconceptions regarding childhood phimosis. Textbooks still teach that male children should have retractable foreskin by age 3. Young children are referred for evaluation for phimosis, which is a commonly used diagnosis for postneonatal circumcision.

We found a high prevalence of physiologic phimosis in kindergarten children, up to 44% at age 6. We also reviewed the incidence of other congenital abnormalities in this coastal Chinese city. The management and complications of these conditions were analyzed. (Read the full article)

Many children experience the death of a parent during childhood. The long-term consequences of this life event, including school performance, and the importance of the psychosocial circumstances of the home have not been well elucidated in previous studies.

Both maternal and paternal deaths during childhood were associated with lower grades and school failure. Many of the associations (and especially for death due to external causes) were associated with socioeconomic disadvantage and psychosocial problems in the family. (Read the full article)

The familial nature of vesicoureteral reflux (VUR) is well recognized. Several studies have shown that siblings of children with VUR are at much higher risk for reflux than the general pediatric population with a reported prevalence between 26% and 50%.

There is increased risk of renal cortical abnormalities in siblings with a previous urinary tract infection, siblings with high-grade VUR, and siblings >1 year of age. This information may be useful when counseling parents about the risk of familial VUR. (Read the full article)

Noonan syndrome is associated with a bleeding diathesis and abnormal coagulation tests.

Bleeding diathesis in Noonan syndrome was evaluated by using a validated bleeding score. For the first time, platelet function was fully investigated, and a significant prevalence of platelet abnormalities likely to contribute to the bleeding diathesis was found. (Read the full article)

Congenital pulmonary malformations are mostly identified prenatally. At birth, some children develop respiratory distress, which may be sufficiently severe to require mechanical ventilation and immediate surgery. The factors predictive of neonatal respiratory distress are not well defined.

Malformation volume and prenatal signs of intrathoracic compression are significant risk factors for respiratory complications at birth in fetuses with pulmonary malformations. In such situations, the delivery should take place in a tertiary care center. (Read the full article)

Inadequate nutrient intake can compromise a child’s nutritional status, which may affect immune function. Improving dietary intake via a follow-up formula may support appropriate immune responses and improve a child’s ability to resist infection.

Children who consumed an experimental follow-up formula had fewer episodes and shorter duration of acute respiratory infections, as well as less antibiotic treatment, and fewer days missed of day care due to illness. (Read the full article)

Massachusetts implemented a major health reform in 2006 to reduce uninsurance, improve access to care, and increase financial protection for its citizens, but little is known about its effect on privately and publicly insured children with special health care needs.

Massachusetts health reform improved access to specialists for privately insured children with special health care needs but did not reduce uninsurance, increase access to primary care, or improve financial protection. National reform may produce similarly modest outcomes for these children. (Read the full article)

After neonatal extracorporeal membrane oxygenation treatment, children are at risk for neurodevelopmental problems including delayed motor function. So far this has only been studied cross-sectionally until age 7 years.

We describe, in a nationwide evaluation, the longitudinal course of motor function development after neonatal extracorporeal membrane oxygenation with persisting problems up to 12 years. At risk are children with congenital diaphragmatic hernia and those with chronic lung disease. (Read the full article)

Infants with Prader-Willi syndrome suffer from hypotonia, muscle weakness, and motor developmental delay and have increased fat mass combined with decreased muscle mass. Growth hormone improves body composition and motor development.

Ultrasound scans confirmed decreased muscle thickness in infants with Prader-Willi syndrome, which improved as result of growth hormone treatment. Muscle thickness was correlated to muscle strength and motor performance. Catch-up growth in muscle thickness was related to muscle use independent of growth hormone. (Read the full article)

Syndrome-specific standardized growth curves are not currently available for non–growth hormone–treated subjects with Prader-Willi syndrome and are required for monitoring growth and development in this rare obesity-related disorder.

Standardized growth curves were useful in monitoring growth and development in these subjects with Prader-Willi syndrome and for the management of growth hormone treatment of both genders, particularly those aged 3 to 18 years. (Read the full article)

More than 70% of all preterm deliveries are late preterm (34–36 weeks of gestation). Existing evidence suggests that compared with those born at term, those born late preterm score lower on neurocognitive tests in childhood and young adulthood.

The effect of late preterm birth on neurocognitive performance persists up to late adulthood, especially among those who have only a basic or upper secondary level of education. Late preterm birth is also associated with a risk of memory impairments. (Read the full article)

Distribution of infant formula discharge packs to breastfeeding mothers is common practice in maternity care facilities in the United States. Receiving discharge packs is associated with shortened exclusive breastfeeding duration. Many efforts have been made to discourage this practice.

From 2007 to 2013, there has been a marked reduction in distribution of discharge packs containing infant formula to breastfeeding mothers in hospitals and birth centers in the United States. (Read the full article)

Dyslexia has a lifelong impact on learning. The consensus in the literature from clinical studies is that dyslexia is not caused by vision abnormalities. However, interventions and therapies directed at eye-related functions are still available.

In this cohort the majority of dyslexic children had normal results for all ophthalmic tests. These population-based data support the consensus that dyslexia is not primarily a vision problem and that vision-based therapies are not justified or likely to help. (Read the full article)

Hospital quality-of-care measures are publicly reported to inform consumer choice and stimulate quality improvement. The number of hospitals and states with a sufficient number of pediatric hospital discharges to detect worse-than-average pediatric inpatient care quality remains unknown.

Most children are admitted to hospitals in which all-condition measures of inpatient quality are powered to show differences in performance from average, but most condition-specific measures are not. Policy on incentives for pediatric inpatient quality should take these findings into account. (Read the full article)

Weak recommendations exist to guide emergent neuroimaging decisions in children with first, unprovoked seizures. The prevalence of and risk factors associated with clinically relevant abnormalities on neuroimaging have not been well defined in prospective studies.

Clinically relevant intracranial abnormalities on neuroimaging occur in 11% of children with first, unprovoked seizures. Emergent/urgent abnormalities, however, occur in <1%, suggesting that most of these children do not require emergent neuroimaging. Specific clinical findings identify patients at higher risk. (Read the full article)

Rudeness is routinely experienced by hospital-based medical teams. Individuals exposed to mildly rude behavior perform poorly on cognitive tasks, exhibit reduced creativity and flexibility, and are less helpful and prosocial.

Rudeness had adverse consequences on diagnostic and procedural performance of members of the NICU medical teams. Information-sharing mediated the adverse effect of rudeness on diagnostic performance, and help-seeking mediated the effect of rudeness on procedural performance. (Read the full article)

16 May 2013The Regulatory Reform (Scotland) Bill was introduced in the Scottish Parliament on 27 March 2013. This briefing provides background information on existing regulatory regimes, and the introduction of the Bill.

24 October 2013The Procurement Reform (Scotland) Bill aims to establish a national legislative framework for public procurement in Scotland. This Briefing sets out the background to the Bill and summarises its main provisions.

13 January 2013This briefing provides a summary of the parliamentary scrutiny of the Regulatory Reform (Scotland) Bill prior to Stage 3 proceedings which are scheduled to take place on 16 January 2014.

8 May 2014This briefing summarises Stage 1 and Stage 2 consideration of the Procurement (Reform) (Scotland) Bill, introduced in the Parliament on 3rd October 2013.

Pennsylvania College of Technology’s National Sustainable Structures Center is adding a training site in Westmoreland County to enhance delivery of building science and energy efficiency training for the U.S. Department of Energy’s Weatherization Assistance Program.

Participate in a chat about how multimedia tools are transforming teaching and learning in core academic subjects.

Two things are true as I sort through my reflections on transformative learning experiences: We need intensive, immersive opportunities for learning (such as a trip to Kenya) and we also need to build in mini-opportunities for transformative learning every day.

Initial draft of the technology framework. Informal document by the Chair

Informal document containing the draft elements of the draft decision on the work programme under the framework for non-market approaches referred to in Article 6, paragraph 8, of the Paris Agreement. Informal document by the Chair.

Informal document containing the draft elements of the rules, modalities and procedures for the mechanism established by Article 6, paragraph 4, of the Paris Agreement. Informal document by the Chair.

Informal document containing the draft elements of guidance on cooperative approaches referred to in Article 6, paragraph 2, of the Paris Agreement. Informal document by the Chair.

Draft elements of the modalities, work programme and functions of the forum on the impact of the implementation of response measures under the Paris Agreement . Informal document by the Chairs.

Unless the government revives land governance reform in Burundi, long-term peacebuilding efforts will remain compromised.

Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1->3)-β-D-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo efficacy of ibrexafungerp (SCY) alone and in combination with anti-mould triazole isavuconazole (ISA) against invasive pulmonary aspergillosis (IPA). The combination of ibrexafungerp and isavuconazole in in vitro studies resulted in an additive and synergistic interactions against Aspergillus spp. Plasma concentration-time curves of ibrexafungerp were compatible with linear dose proportional profile. In vivo efficacy was studied in a well established persistently neutropenic NZW rabbit model of experimental IPA. Treatment groups included untreated rabbits (UC) and rabbits receiving ibrexafungerp at 2.5(SCY2.5) and 7.5(SCY7.5) mg/kg/day, isavuconazole at 40(ISA40) mg/kg/day, or combinations of SCY2.5+ISA40 and SCY7.5+ISA40. The combination of SCY+ISA produced in vitro synergistic interaction. There was significant in vivo reduction of residual fungal burden, lung weights, and pulmonary infarct scores in SCY2.5+ISA40, SCY7.5+ISA40, and ISA40-treatment groups vs that of SCY2.5-treated, SCY7.5-treated and UC (p<0.01). Rabbits treated with SCY2.5+ISA40 and SCY7.5+ISA40 had prolonged survival in comparison to that of SCY2.5-, SCY7.5-, ISA40-treated or UC (p<0.05). Serum GMI and (1->3)-β-D-glucan levels significantly declined in animals treated with the combination of SCY7.5+ISA40 in comparison to those treated with SCY7.5 or ISA40 (p<0.05). Ibrexafungerp and isavuconazole combination demonstrated prolonged survival, decreased pulmonary injury, reduced residual fungal burden, lower GMI and (1->3)-β-D-glucan levels in comparison to those of single therapy for treatment of IPA. These findings provide an experimental foundation for clinical evaluation of the combination of ibrexafungerp and an anti-mould triazole for treatment of IPA.

Mucormycosis is a life-threatening infection with high mortality that occurs predominantly in immunocompromised patients. Manogepix (MGX) is a novel antifungal that targets Gwt1, an early step in the conserved glycosylphosphotidyl inositol (GPI) post-translational modification pathway of surface proteins in eukaryotic cells. Inhibition of inositol acylation by MGX results in pleiotropic effects including inhibition of maturation of GPI-anchored proteins necessary for growth and virulence. MGX has been previously shown to have in vitro activity against some strains of Mucorales. Here we assessed the in vivo activity of the prodrug fosmanogepix, currently in clinical development for the treatment of invasive fungal infections, against two Rhizopus arrhizus strains with high (4.0 μg/ml) and low (0.25 μg/ml) minimum effective concentration (MEC) values. In both invasive pulmonary infection models, treatment of mice with 78 mg/kg or 104 mg/kg fosmanogepix, along with 1-aminobenzotriazole to enhance the serum half-live of MGX in mice, significantly increased median survival time and prolonged overall survival by day 21 post infection when compared to placebo. In addition, administration of fosmanogepix resulted in a 1-2 log reduction in both lung and kidney fungal burden. For the 104 mg/kg fosmanogepix dose, tissue clearance and survival were comparable to clinically relevant doses of isavuconazole (ISA), which is FDA approved for the treatment of mucormycosis. These results support continued development of fosmanogepix as a first in class treatment for invasive mucormycosis.

Multidrug resistant strains belonging to the Enterobacter cloacae complex (ECC) group, and especially those belonging to clusters C-III, C-IV and C-VIII, have increasingly emerged as a leading cause of healthcare-associated infections, with colistin used as one of the last line of treatment. However, colistin-resistant ECC strains have emerged. The aim of this study was to prove that MgrB, the negative regulator of PhoP/PhoQ two-component regulatory system, is involved in colistin resistance in ECC of cluster C-VIII, formerly referred to as Enterobacter hormaechei subsp. steigerwaltii. An in vitro mutant (Eh22-Mut) was selected from a clinical isolate of Eh22. The sequencing analysis of its mgrB gene showed the presence of one nucleotide deletion leading to the formation of a truncated protein of six instead of 47 amino acids. Wild-type mgrB gene from Eh22, as well as that of a clinical strain of Klebsiella pneumoniae used as controls, were cloned and the corresponding recombinant plasmids were used for complementation assays. Results showed a fully restored susceptibility to colistin, and confirmed for the first time that mgrB gene expression plays a key role in acquired resistance to colistin in ECC strains.

Probiotics might provide an alternative approach for the control of oral candidiasis. However, studies on the antifungal activity of probiotics in the oral cavity are based on the consumption of yogurt or other dietary products, and there is a necessary to use appropriate biomaterials and specific strains to obtain probiotic formulations targeting local oral administration. In this study, we impregnated gellan gum, a natural biopolymer used as a food-additive, with a probiotic and investigated its antifungal activity against Candida albicans. Lactobacillus paracasei 28.4, a strain recently isolated from the oral cavity of a caries-free individual, was incorporated in several concentrations of gellan gum (0.6% to 1%). All tested concentrations could incorporate L. paracasei cells while maintaining bacterial viability. Probiotic/gellan formulations were stable for 7 days when stored at room temperature or 4°C. Long-term storage of bacteria-impregnated gellan gum was achieved when L. paracasei 28.4 was lyophilized. The probiotic/gellan formulations provided a release of L. paracasei cells over 24 hours that was sufficient to inhibit the growth of C. albicans with effects dependent on the cell concentrations incorporated into gellan gum. The probiotic/gellan formulations also had inhibitory activity against Candida spp. biofilms by reducing the number of Candida spp. cells (p < 0.0001), decreasing the total biomass (p = 0.0003), and impairing hyphae formation (p = 0.0002), compared to the control group which received no treatment. Interestingly, probiotic formulation of 1% w/v gellan gum provided an oral colonization of L. paracasei in mice with approximately 6 log of CFU/mL after 10 days. This formulation inhibited the C. albicans growth (p < 0.0001), prevented the development of candidiasis lesions (p = 0.0013), and suppressed inflammation (p = 0.0006) when compared to the mice not treated in the microscopic analysis of the tongue dorsum. These results indicate that gellan gum is a promising biomaterial and can be used as a carrier system to promote oral colonization for probiotics that prevent oral candidiasis.

Treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP+Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) at 4-day intervals, plus allopurinol at 30 mg/kg/12 h p.o. during 130 days; LC+Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose), plus allopurinol during 130 days; Allop, treated with allopurinol only; non-treated control. Parasite loads were evaluated by quantitative PCR in liver, spleen and bone marrow and by immunohistochemistry in the ear skin, before, just after treatment and 4 months later. LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen and bone marrow 4 months after treatment, compared to the pre-treatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin, in comparison to the control group. On the basis of clinical staging and parasitological evaluations, LCP formulation exhibited a more favorable therapeutic profile, when compared to LC one, being therefore promising for treatment of canine visceral leishmaniasis.

One of the reasons for the lengthy tuberculosis (TB) treatment is the difficult to treat non-multiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models in our pre-clinical drug development pipeline. In most available dormancy models it takes a long time to create a dormant state and it is difficult to identify and quantify this non-multiplying condition.

The Mycobacterium tuberculosis 18b strain might overcome some of these problems, because it is dependent on streptomycin for growth and becomes non-multiplying after 10 days of streptomycin starvation, but still can be cultured on streptomycin-supplemented culture plates. We developed our 18b dormancy time-kill kinetic model to assess the difference in the activity of isoniazid, rifampicin, moxifloxacin and bedaquiline against log-phase growth compared to the non-multiplying M. tuberculosis subpopulation by CFU counting including a novel AUC-based approach as well as time-to-positivity (TTP) measurements.

We observed that isoniazid and moxifloxacin were relatively more potent against replicating bacteria, while rifampicin and high dose bedaquiline were equally effective against both subpopulations. Moreover, the TTP data suggest that including a liquid culture-based method could be of additional value as it identifies a specific mycobacterial subpopulation that is non-culturable on solid media.

In conclusion, the results of our study underline that the time-kill kinetics 18b dormancy model in its current form is a useful tool to assess TB drug potency and thus has its place in the TB drug development pipeline.

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC_0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (V_d) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC_0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC_0-24 and lower CL compared to other phases for both drugs. The V_d for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

BACKGROUND:

The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated.

OBJECTIVES:

Our first aim was to examine baseline differences in body dissatisfaction, depression, and anxiety symptoms by gender, age, and Tanner (ie, pubertal) stage. Our second aim was to test for changes in youth symptoms over the first year of receiving gender-affirming hormone therapy. Our third aim was to examine potential differences in change over time by demographic and treatment characteristics. Youth experiences of suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) are also reported.

With the UEFA Champions League resuming next week, UEFA.com looks at which players have been hitting the heights on the domestic front.

An Albanian man's heart is forever changed after suffering a heart attack and meeting Jesus in his recuperation.

The UEFA Futsal EURO is to be expanded to 16 teams and will become a tournament played every four years, starting from 2022.

An Albanian man's heart is forever changed after suffering a heart attack and meeting Jesus in his recuperation.

The UEFA Futsal EURO is to be expanded to 16 teams and will become a tournament played every four years, starting from 2022.

An Albanian man's heart is forever changed after suffering a heart attack and meeting Jesus in his recuperation.

Former Hearts chairman Leslie Deans has urged the club to take legal action against the SPFL as well as those who voted to end the season early, effectively relegating the Jambos.

David Gozal
Sep 1, 1998; 102:616-620
ARTICLES