Dilemma in Differentiating between Acute Osteomyelitis and Bone Infarction in Children with Sickle Cell Disease: The Role of Ultrasound

Background

Distinguishing between acute presentations of osteomyelitis (OM) and vaso-occlusive crisis (VOC) bone infarction in children with sickle cell disease (SCD) remains challenging for clinicians, particularly in culture-negative cases. We examined the combined role of ultrasound scan (USS), C - reactive protein and White blood counts (WCC) in aiding early diagnosis in children with SCD presenting acutely with non-specific symptoms such as bone pain, fever or swelling which are common in acute osteomyelitis or VOC.

Methods

We reviewed the records of all children with SCD who were discharged from our department from October 2003 to December 2010 with a diagnosis of osteomyelitis based on clinical features and the results of radiological and laboratory investigations. A case control group with VOC who were investigated for OM were identified over the same period.

Results

In the osteomyelitis group, USS finding of periosteal elevation and/or fluid collection was reported in 76% cases with the first scan (day 0–6). Overall 84% were diagnosed with USS (initial +repeat). 16% had negative USS. With VOC group, USS showed no evidence of fluid collection in 53/58 admissions (91%), none of the repeated USS showed any fluid collection. Mean C-reactive protein (CRP), and white cell count (WCC) were significantly higher in the OM.

Conclusion

The use of Ultrasound in combination with CRP and WCC is a reliable, cost-effective diagnostic tool for differentiating osteomyelitis from VOC bone infarction in SCD. A repeat ultrasound and/or magnetic resonance imaging (MRI) scan may be is necessary to confirm the diagnosis.     

Development of Overweight in Children in Relation to Parental Weight and Socioeconomic Status

The purpose of the study was to test the hypothesis that socioeconomic status (SES) moderates the association between parental weight and changes in BMI from childhood to early adolescence. Participants included 428 twin children from 100 families with obese parents (“obese families”) and 114 sociodemographically matched families with normal‐weight parents (“lean families”) who were assessed in their homes (age = 4.4). Follow‐up study was conducted 7 years later (age = 11.2) on 346 children (81%). Complete data were available for 333 children. Family SES was indexed with maternal education. Children's weights and heights were measured to calculate BMI s.d. scores based on 1990 British norms. Overweight was defined as >91st BMI centile. In children with obese parents, BMI s.d. scores increased from 0.51 at age 4 to 1.06 at age 11. In children with lean parents, BMI s.d. scores decreased from 0.11 to 0.05. Prevalence of overweight remained stable from age 4 to 11 in children with lean parents (8% to 9%), but it more than doubled in children with obese parents (17% to 45%). There was a significant interaction between parental weight and family SES (P < 0.01), so that in children with lean parents there was no SES difference in the BMI status from age 4 to 11; however, in children with obese parents, the increase in adiposity was significantly greater in lower SES families. These results suggest that parental leanness confers significant protection against development of overweight in children regardless of family SES, while parental obesity is an adverse prognostic sign, especially in lower SES families.     

Polymorphisms in the 3′-UTR of <Emphasis Type="Italic">SCD5</Emphasis> gene are associated with hepatocellular carcinoma in Korean population

The purpose of the study was to assess the relationship between polymorphisms of the SCD5 and MMP1 gene and hepatocellular carcinoma (HCC). The gene polymorphisms with a minor allele frequency (MAF)?>?0.05 were selected eight SNPs (rs6840, rs1065403, rs3821974, and rs3733230 in 3?-UTR; rs4693472, rs3733227, rs1848067, and rs6535374 in intron region) of SCD5 gene and two SNPs (rs1799750 and rs1144393 in promoter region) of MMP1 gene. The genotype of SCD5 and MMP1 gene SNPs were determined by direct sequencing and pyrosequencing, respectively. One hundred sixty-two patients with HCC and two hundred twenty-five control subjects were recruited in Korean male population. In terms of genotype frequencies, SCD5 genotype TC, GA, AG, and CG of rs6840, rs1065403, rs3821974, and rs3733230, respectively were higher in control group than HCC. In addition, these genotype decreased the risk (rs6840; OR 0.55, 95% CI 0.31–0.99; rs1065403; OR 0.46, 95% CI 0.26–0.83; rs3821974; OR 0.56, 95% CI 0.31–0.99; rs3733230; OR 0.62, 95% CI 0.34–1.12) of HCC, which may work as a prevention of HCC. At least one minor allele carrier of SCD5 gene polymorphisms were related to decreased risk of HCC for AFP cut-point levels >?200 or >?400 ng/ml, respectively. Our results indicate that polymorphisms in the 3?-UTR of the SCD5 gene may associated with HCC in the Korean male population.     

Economic growth and obesity: An interesting relationship with world-wide implications

The prosperity of a country, commonly measured in terms of its annual per capita Gross Domestic Product (GDP), has different relationships with population levels of body weight and happiness, as well as environmental impacts such as carbon emissions. The aim of this study was to examine these relationships and to try to find a level of GDP, which provides for sustainable economic activity, optimal happiness and healthy levels of mean body mass index (BMI). Spline regression analyses were conducted using national indices from 175 countries: GDP, adult BMI, mean happiness scores, and carbon footprint per capita for the year 2007. Results showed that GDP was positively related to BMI and happiness up to ∼$US3000 and ∼$5000 per capita respectively, with no significant relationships beyond these levels. GDP was also positively related to CO₂ emissions with a recognised sustainable carbon footprint of less than 5 tonnes per capita occurring at a GDP of <$US15,000. These findings show that a GDP between $US5 and $15,000 is associated with greater population happiness and environmental stability. A mean BMI of 21-23 kg/m², which minimises the prevalence of underweight and overweight in the population then helps to define an ideal position in relation to growth, which few countries appear to have obtained. Within a group of wealthy countries (GDP > $US30,000), those with lower income inequalities and more regulated (less liberal) market systems had lower mean BMIs.     

Grades of undernutrition and socioeconomic status influence cognitive development in school children of Kolkata

Cognitive development of children is influenced by different environmental factors like nutritional and socio‐economic status. The objectives of the present study were to determine the influence of grades of undernutrition and socio‐economic status (SES) on the cognitive development of school children of Kolkata. Five hundred sixty six (566) school children having 5–12 years of age were selected from different schools of Kolkata. The cognitive development was measured by the scores of Raven's colored progressive matrices (RCPM). The chronic and acute nutritional statuses were measured from height‐for‐age (HAZ) and weight‐for‐age (WAZ) Z scores respectively with reference to the values of WHO. SES was determined by updated Kuppuswamy scale. The prevalences of undernutrition in the observed children were 57.95% (according to HAZ) and 52.82% (according to WAZ). The age dependent growth curve of RCPM scores of the observed children remains in between the 10th and 25th centile of British children. The children belonging to superior and intellectual deficit IQ classes were 21.55 and 36.40%, respectively of the total subjects. Most of the subjects belong to lower middle (39.93%) and upper middle (36.40%) class of SES. RCPM scores of school children were gradually decreased with the grades of undernutrition and SES. RCPM scores were significantly correlated with HAZ, WAZ, SES, age, and sex (P < 0.001) and strongly associated with HAZ, SES, age, and sex (P < 0.001, P < 0.05). Present study indicates that cognitive development of school children of Kolkata is influenced by the grade of undernutrition and SES. Am J Phys Anthropol 156:274–285, 2015. © 2014 Wiley Periodicals, Inc.     

Post‐marketing observational study on 5% intravenous immunoglobulin therapy in patients with secondary immunodeficiency and recurrent serious bacterial infections

Secondary hypogammaglobulinemia is one of the factors responsible for the increased susceptibility to infection in patients with chronic lymphocytic leukemia (CLL). This study assessed the therapeutic results, concomitant medication and tolerance of administering 5% intravenous immunoglobulin, secondary immunodeficiency and recurrent serious bacterial infections. A single center, post‐marketing, observational clinical study was performed on 10 patients with a variety of hematological malignancies (CLL, follicular non‐Hodgkin lymphoma, IgM‐secreting immunocytoma, IgA plasmacytoma and myelodysplastic syndrome/non‐Hodgkin lymphoma) who had been infused with IVIG from June 1994 to May 2009. The clinical benefit of IVIG was assessed by comparing the incidence of bacterial infections before and after starting this therapy. Plasma immunoglobulin concentrations and relevant hematological variables were recorded. For safety assessment, adverse events were monitored. The standard IVIG dosage was approximately 0.35 g/kg body weight every 3–4 weeks. Most patients had normal IgG trough values of >600 mg/dL during the IVIG treatment period. The rate of bacterial infections was reduced from 2.4 per patient in the 3 months before IVIG to 0.7 (0–1.5) per patient per year during IVIG treatment. All patients received concomitant medication, mainly anticancer and anti‐anemia therapy (100%). No serious adverse events related to IVIG were observed. The frequency of at least one minor adverse reaction was 1.44% (8/556 infusions). In conclusion, the investigated IVIG preparation was well tolerated and clinically beneficial in reducing the long term rate of serious bacterial infections in patients receiving concomitant treatment for malignant diseases.     

Co-Inheritance of alpha-thalassemia and sickle cell disease in a cohort of Angolan pediatric patients

Molecular Biology Reports - The aim of this study was to explore the association between alpha-thalassemia, fetal hemoglobin, hematological indices, and clinical adverse events in Angolan sickle...     

Plasma stearoyl‐CoA desaturase indices: Association with lifestyle,diet, and body composition

Objective:

Stearoyl‐coenzyme A desaturase‐1 (SCD1) is a key enzyme in fatty acid and energy metabolism. Increased hepatic SCD1 activity is associated with obesity and obesity‐related diseases. We examined the relations of two plasma SCD activity indices (16:1n‐7/16:0, 18:1n‐9/18:0) with body composition, and the association of lifestyle and dietary variables with the plasma SCD indices.

Design and Methods:

This population‐based, cross‐sectional study of 2021 elderly (71–74 y) men and women from the Hordaland Health Study in Western Norway was conducted using a validated food frequency questionnaire, body composition measurements by dual‐energy X‐ray absorptiometry and determination of the plasma fatty acid profile.

Results:

In multivariate regression analyses, plasma SCD indices were positively associated with BMI and body fat (P < 0.001 for both). From the 2.5th to 97.5th percentiles of plasma SCD‐16 and SCD‐18 indices, fat mass differed by about 8 kg and 5 kg, respectively. Intake of polyunsaturated fatty acids were negatively associated with SCD‐16 (partial r = ?0.30) and SCD‐18 (partial r = ?0.24) (P < 0.001 for both). Alcohol intake was positively associated with SCD‐16 (partial r = 0.26) and SCD‐18 (partial r = 0.16) (P < 0.001 for both), whereas coffee consumption and physical activity were inversely associated with SCD‐16 (P = 0.026 and P = 0.006, respectively) and SCD‐18 (P = 0.001 and P = 0.022, respectively).

Conclusions:

In this elderly population, plasma markers of SCD1 activity are associated with increased adiposity. Furthermore, modifiable dietary habits and lifestyle are associated with plasma SCD indices. These results suggest that SCD1 activity may be a promising target for weight control.

     

Socioeconomic status and adiposity in childhood: a systematic review of cross-sectional studies 1990-2005

Background: Sobal and Stunkard's review (1989) of 34 studies from developed countries published after 1941, found inconsistent relationships between socioeconomic status (SES) and childhood adiposity. Inverse associations (36%), no associations (38%), and positive associations (26%) were found in similar proportions. In view of the trends in pediatric obesity, the relationship between SES and adiposity may have changed. Objective: To describe the cross‐sectional association between SES and adiposity in school‐age children from western developed countries in epidemiological studies since 1989. Methods and Procedures: PubMed database was searched to identify potentially relevant publications. Epidemiological studies from western developed countries presenting cross‐sectional data on the bivariate association between an SES indicator and objectively measured adiposity in childhood (5–18 years), carried out after 1989 were included. SES indicators included parental education, parental occupation, family income, composite SES, and neighborhood SES. Results: Forty‐five studies satisfied the review criteria. SES was inversely associated with adiposity in 19 studies (42%), there was no association in 12 studies (27%), and in 14 studies (31%) there was a mixture of no associations and inverse associations across subgroups. No positive SES‐adiposity associations were seen in unadjusted analyses. With parental education as the SES indicator, inverse associations with adiposity were found in 15 of 20 studies (75%). Discussion: Research carried out within the past 15 years finds that associations between SES and adiposity in children are predominately inverse, and positive associations have all but disappeared. Research is needed to understand the mechanisms through which parental social class influences childhood adiposity.     

Conversion of systemically-distributed triazole-based stearoyl-CoA desaturase (SCD) uHTS hits into liver-targeted SCD inhibitors

It has been demonstrated that once-a-day dosing of systemically-distributed SCD inhibitors leads to adverse events in eye and skin. Herein, we describe our efforts to convert a novel class of systemically-distributed potent triazole-based uHTS hits into liver-targeted SCD inhibitors as a means to circumvent chronic toxicity.     

Carbonic anhydrase inhibitors: Synthesis and inhibition of the human carbonic anhydrase isoforms I,II, VII,IX and XII with benzene sulfonamides incorporating 4,5,6,7-tetrabromophthalimide moiety

A series of 4,5,6,7-tetrabromo-1,3-dioxoisoindolin-2-yl benzenesulfonamide derivatives (compounds 1–8) was synthesized by reaction of benzene sulfonamide derivatives with 4,5,6,7-tetrabromophthalic anhydride moiety. These new sulfonamides were investigated as inhibitors of the zinc metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more specifically against the human (h) cytosolic isoforms hCA I, II and VII and the transmembrane tumor-associated isoform hCA IX and XII. The new compounds were good hCA I inhibitors (Kis in the range of 143 to >10,000 nM), but were moderately effective, as hCA II inhibitors (Kis of 47–190 nM) and poor hCA VII inhibitors (Kis in the range of 54–175 nM) compared to acetazolamide. The tumor-associated hCA IX was effectively inhibited with Kis ranging between 8.5 and 234 nM and hCA XII with inhibition constants in the range of 6.1–197 nM with high selectivity ratio. The structure–activity relationship (SAR) with this series of sulfonamides is straightforward, with the main features leading to good activity for each isoforms being established. The high sequence hCA alignment homology and molecular docking study of compounds was performed to rationalize the SAR reported over here.     

Trends in Child Overweight Rates and Energy Intake in France From 1999 to 2007: Relationships With Socioeconomic Status

Our objectives were (i) to assess the current prevalence of childhood overweight (including obesity) (OWOB) in France and its relationship with comprehensive socioeconomic status (SES) indicators and (ii) to examine trends in OWOB prevalence and changes in energy intake (EI) and sedentary behavior (SED) based on the previous INCA 1 (Individuelle Nationale des Consommations Alimentaires) data (1998–1999). A representative sample of children aged 3–14 (n = 1,030) was taken from the 2006–2007 cross‐sectional INCA 2 food consumption survey. Weight and height were measured. The prevalence of OWOB was estimated according to the IOTF (International Obesity Task Force) definition. Average daily EI was evaluated using a 7‐day food record. SED (screen time) and SES were reported by answering questionnaires. SES indicators included the occupation and level of education of the head of the household (HH), and variables describing household wealth. Composite indices of SES were computed by correspondence analysis, and relationships with OWOB were explored by logistic regression analysis. In total, 14.5% (95% CI: 12.1–17.0) of the children were OWOB. All SES indicators were inversely correlated to OWOB. Average EI was equal to 1,739 kcal/day. Daily, children spent 113.5 min watching television, and 38.5 min playing video games or using a computer. Compared to the INCA 1 study, OWOB prevalence was not significantly different, EI was lower, and SED was higher. These trends were the same across all occupational categories of heads of household. Although overall rates of childhood OWOB are currently stabilizing, no change was observed in the strong inverse socioeconomic gradient of OWOB between the two studies.     

The socioeconomic gradient in child health and noncognitive skills: Evidence from the Czech Republic

We investigate the presence of a socioeconomic status (SES) gradient in children’s health and noncognitive skill development, and its evolution with child age using cohort data from the Czech Republic. We show that family SES are positively associated with better child health. These effects start to emerge at age 3 and are persistent for all subsequent ages. We find a modest strengthening of the gradient as the children grow older. Similarly, at the lowest distribution of average family income, children lag in their noncognitive skills. We find evidence that children enter school with substantial differences in noncognitive skill endowments based on family SES. This correlation persists when controlling for poor health at birth, the roles of specific and chronic health problems, housing conditions, and partner characteristics. Maternal health status explains some of the association between family income and child noncognitive skills. We account for the endogeniety of SES and non-linearities in measures.     

Design,synthesis and evaluation of highly selective pyridone-based class II MET inhibitors

The high incidence of MET oncogene activation in human malignancies has prompted researchers to develop MET inhibitors. As part of our efforts to developing effective and safe therapeutic agents against MET-dependent tumors, a pyridone-based class II MET inhibitor, namely, 1-(4-((2-amino-3-iodopyridin-4-yl)-oxy)-3-fluorophenyl)-N-(4-fluorobenzyl)-4-methoxy-6-oxo-1,6-dihydropyridine-3-carboxamide (3s), was identified. Knowledge of the binding mode of class II MET inhibitors led to the design of new inhibitors that utilize 2-pyridone to conformationally restrain key pharmacophoric groups within the molecule. Integrated molecular docking and SAR studies resulted in the discovery of a novel class of pyridone MET inhibitors with high potency (IC₅₀ of 0.005 μM) and efficient selectivity (>5000 fold) to VEGFR-2, c-Kit and RET kinases.     

Nutritional determinants of high-altitude growth in nuñoa,Peru

Data on nutritional intake and patterns of physical growth in the rural Andean community of Nuñoa, Peru (elevation 4,000 m), are described and compared to data previously collected from this location. Food consumption data and selected anthropometric measures were obtained from a sample of 33 households. Estimates of caloric intake from this study are very similar to those obtained in Nuñoa during the mid- and late 1960s. However, within the present sample, upper income (i.e., middle class) individuals have significantly higher caloric intakes than those of the lower income group and also appear to have an improved diet relative to individuals of 20 years ago. Anthropometric data show that children of the upper socioeconomic status (SES) group are significantly taller and heavier than the lower SES group children. Moreover, the children of the wealthier families are taller and heavier than the children measured 20 years ago at the same location, whereas the poorer children are not. These results indicate that nutritional factors have significantly contributed to the extreme pattern of slow growth previously reported for children of Nuñoa and, moreover, demonstrate how social and environmental forces interact to create differential levels of stress that contribute to variation in biological well-being.     

Freeze–thaw processes and intense rainfall: the one-two punch for high sediment and nutrient loads from mid-Atlantic watersheds

Large runoff, sediment, and nutrient exports from watersheds could occur due to individual extreme climate events or a combination of multiple hydrologic and meteorological conditions. Using high-frequency hydrologic, sediment, and turbidity data we show that freeze–thaw episodes followed by intense winter (February) rainstorms can export very high concentrations and loads of suspended sediment and particulate organic carbon (POC) and nitrogen (PN) from mid-Atlantic watersheds in the US. Peak suspended sediment (> 5000 mg L^?1), POC (> 250 mg L^?1) and PN (> 15 mg L^?1) concentrations at our 12 and 79 ha forested watersheds for the February rainfall-runoff events were highest on record and the fluxes were comparable to those measured for tropical storms. Similar responses were observed for turbidity values (> 400 FNU) at larger USGS-monitored watersheds. Much of the sediments and particulate nutrients likely originated from erosion of stream bank sediments and/or channel storage. Currently, there is considerable uncertainty about the contribution of these sources to nonpoint source pollution, particularly, in watersheds with large legacy sediment deposits. Future climate projections indicate increased intensification of storm events and increased variability of winter temperatures. Freeze–thaw cycles coupled with winter rain events could increase erosion and transport of streambank sediments with detrimental consequences for water quality and health of downstream aquatic ecosystems.     

The impact of health insurance affiliation and socioeconomic status on cervical cancer survival in Bucaramanga,Colombia

Cervical cancer is still an important cause of death in countries like Colombia. We aimed to determine whether socioeconomic status of residential address (SES) and type of health insurance affiliation (HIA) might be associated with cervical cancer survival among women in Bucaramanga, Colombia. All patients residing in the Bucaramanga Metropolitan Area diagnosed with invasive cervical cancer (ICD-0–3 codes C53.X) between 2008 and 2016 (n = 725) were identified through the population-based cancer registry, with 700 women having follow-up data for >5 years (date of study closure: Dec 31, 2021), yielding an overall 5-year survival estimate (95 % CI) of 56.4 % (52.7 – 60.0 %). KM estimates of 5-year overall survival were obtained to assess differences in cervical cancer survival by SES and HIA. Multivariable Cox-proportional hazards modeling was also conducted, including interaction effects between SES and HIA. Five-year overall survival was lower when comparing low vs. high SES (41.9 % vs 57.9 %, p < 0.0001) and subsidized vs. contributive HIA (45.1 % vs 63.0 %, p < 0.0001). Multivariable Cox modeling showed increased hazard ratios (HR) of death for low vs. high SES (HR = 1.78; 95 % CI = 1.18–2.70) and subsidized vs. contributive HIA (HR = 1.44; 95 % CI = 1.13–1.83). The greatest disparity in HR was among women of low SES affiliated to subsidized HIA (vs. contributive HIA and high SES) (HR=2.53; 95 % CI = 1.62–3.97). Despite Colombia’s universal healthcare system, important disparities in cervical cancer survival by health insurance affiliation and socioeconomic status remain.     

Evaluation of sugarcane by-product pressmud as a manure in carp culture

The effectiveness of pressmud, a sugarcane by-product, was tested as a manure in the production of natural food and carp, by conducting two experiments. The first experiment, of 5 weeks duration, examined the effect of pressmud addition on water quality and natural food production. This study was carried out in fibreglass tubs (1.54 m3) with a 5 cm mud layer, employing pressmud at dosages of 5000, 10,000 and 15,000 kg ha(-1) for treatments T1, T2 and T3, respectively. Unfertilized tubs served as control (T0). The second experiment of 120-day duration to study the effect on growth, survival and quality of common carp was conducted in 25 m2 cement tanks with 15 cm-mud bottom, using the same dosages of pressmud. The control tanks in this experiment were manured with cattle dung at 10,000 kg ha(-1) (T0). Application of pressmud enhanced (P < 0.05) natural food production, with the greatest effect noted in treatment T3. Fish growth was significantly greater (P < 0.05) in treatments T2 and T3, there being no difference in growth between the control (T0) and 5000 kg pressmud treatment (T1). The greatest survival and production were obtained under treatment T2, which indicates that the dosage of 10,000 kg ha(-1) pressmud is optimal for carp culture. A significant effect (P < 0.05) of pressmud on carcass protein was observed. Organoleptic quality of both raw flesh and cooked meat of carp was not affected (P > 0.05) by pressmud treatment.     

Trends in physical stature across socioeconomic groups of Chilean boys, 1880–1997

This paper studies the trends in height-by-age across socioeconomic groups of Chilean boys aged 5–18 born between 1880 and 1997, by performing a meta-analysis of 38 studies reporting height-by-age published since 1898. We estimate the trends using quantile regressions and by analyzing detailed height data from five selected studies. Both methods yield an average decennial increase in height of 1–1.1 cm, and 0.9 and 1.2–1.3 cm for boys of upper and lower socioeconomic status (SES), respectively. SES differences in heights of 9–11 cm are observed up to the late 1940s. However, boys born after the 1930s exhibit substantial convergence in height between socioeconomic groups, driven by an increase in height of middle and lower SES boys of 1.5 and 1.4–2 cm per decade, respectively. As a result, SES differences in height decreased to 5 cm in 1990s. Since these changes occurred in a context of moderate economic growth and persistent income inequality, we argue that our findings are associated with the emergence and expansion of social policies in Chile since the 1940s, which delivered steady improvements in health, nutrition and living conditions.