A new case of sodium-dependent multivitamin transporter defect occurring as a life-threatening condition responsive to early vitamin supplementation and literature review.

BACKGROUND: Biallelic pathogenic variants in SLC5A6 resulting in sodium-dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin-responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms. METHODS: We describe a case report of a 5-month-old girl presenting two recurrent episodes of metabolic decompensation and massive cardiac failure in the course of an infectious disease. We compare clinical, biological, and genetic findings of this patient to previous literature collected from Pubmed database (keywords: Sodium-dependent multivitamin transporter (SMVT), SMVT defect/disorder/deficiency, SLC5A6 gene/mutation). RESULTS: We highlight the life-threatening presentation of this disease, the stagnation of psychomotor development, the severe and persistent hypogammaglobulinemia, and additionally, the successful clinical response on early vitamin supplementation (biotin 15 mg a day and pantothenic acid 100 mg a day). Metabolic assessment showed a persistent increase of urinary 3-hydroxyisovaleric acid (3-HIA) as previously reported in this disease in literature. CONCLUSION: SMVT deficiency is a vitamin-responsive inborn error of metabolism that can lead to a wide range of symptoms. Increased and isolated excretion of urinary 3-hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life-threatening.

Modeling National Embedded Phosphorus Flows of Corn Ethanol Distillers' Grains to Elucidate Nutrient Reduction Opportunities.

Freshwater quality and ecosystem impairment associated with excess phosphorus (P) loadings have led to federally mandated P reduction for certain organic waste streams. Phosphorus reduction from livestock and poultry feeds such as corn ethanol distillers' grains (DGs) presents a centralized strategy for reducing P loss from animal manurein agriculturally intensive states, but little is known about the actual distribution and geospatial P contributions of DGs as animal feed. Here, a county-level flow network for corn ethanol DGs was simulated in the United States to elucidate opportunities for P reduction and the potential for nutrient trading between centralized sources. Overall, the estimated P in DGs that was transferred to US animal feeding operations was nearly twice that present in all human waste prior to treatment. Simulation results suggest that Midwestern states account for an estimated 63% of domestic DG usage, with 72% utilized within the state of production. County-level data were also used to highlight the potential of using nutrient trading markets to incentivize P recovery from DGs at biorefineries within an agriculturally intensive watershed region in Iowa. In summary, corn ethanol biorefineries represent a key leverage point for sustainable P management at the national and local scales.

Jujube Fruit Metabolomic Profiles Reveal Cultivar Differences and Function as Cultivar Fingerprints.

Jujube is a nutritious fruit, and is high in vitamin C, fiber, phenolics, flavonoids, nucleotides, and organic acids. It is both an important food and a source of traditional medicine. Metabolomics can reveal metabolic differences between Ziziphus jujuba fruits from different jujube cultivars and growth sites. In the fall of 2022, mature fresh fruit of eleven cultivars from replicated trials at three sites in New Mexico-Leyendecker, Los Lunas, and Alcalde-were sampled from September to October for an untargeted metabolomics study. The 11 cultivars were Alcalde 1, Dongzao, Jinsi (JS), Jinkuiwang (JKW), Jixin, Kongfucui (KFC), Lang, Li, Maya, Shanxi Li, and Zaocuiwang (ZCW). Based on the LC-MS/MS analysis, there were 1315 compounds detected with amino acids and derivatives (20.15%) and flavonoids (15.44%) as dominant categories. The results reveal that the cultivar was the dominant factor in metabolite profiles, while the location was secondary. A pairwise comparison of cultivar metabolomes revealed that two pairs had fewer differential metabolites (i.e., Li/Shanxi Li and JS/JKW) than all the other pairs, highlighting that pairwise metabolic comparison can be applied for cultivar fingerprinting. Differential metabolite analysis also showed that half of drying cultivars have up-regulated lipid metabolites compared to fresh or multi-purpose fruit cultivars and that specialized metabolites vary significantly between cultivars from 35.3% (Dongzao/ZCW) to 56.7% (Jixin/KFC). An exemplary analyte matching sedative cyclopeptide alkaloid sanjoinine A was only detected in the Jinsi and Jinkuiwang cultivars. Overall, our metabolic analysis of the jujube cultivar's mature fruits provides the largest resource of jujube fruit metabolomes to date and will inform cultivar selection for nutritional and medicinal research and for fruit metabolic breeding.

Integrated Agricultural Practices and Engineering Technologies Enhance Synergies of Food-Energy-Water Systems in Corn Belt Watersheds.

Interconnected food, energy, water systems (FEWS) require systems level understanding to design efficient and effective management strategies and policies that address potentially competing challenges of production and environmental quality. Adoption of agricultural best management practices (BMPs) can reduce nonpoint source phosphorus (P) loads, but there are also opportunities to recover P from point sources, which could also reduce demand for mineral P fertilizer derived from declining geologic reserves. Here, we apply the Integrated Technology-Environment-Economics Model to investigate the consequences of watershed-scale portfolios of agricultural BMPs and environmental and biological technologies (EBTs) for co-benefits of FEWS in Corn Belt watersheds. Via a pilot study with a representative agro-industrial watershed with high P and nitrogen discharge, we show achieving the nutrient reduction goals in the watershed; BMP-only portfolios require extensive and costly land-use change (19% of agricultural land) to perennial energy grasses, while portfolios combining BMPs and EBTs can improve water quality while recovering P from corn biorefineries and wastewater streams with only 4% agricultural land-use change. The potential amount of P recovered from EBTs is estimated as 2 times as much as the agronomic P requirement in the watershed, showing the promise of the P circular economy. These findings inform solution development based on the combination of agricultural BMPs and EBTs for the cobenefits of FEWS in Corn Belt watersheds.

Mapping the National Phosphorus Recovery Potential from Centralized Wastewater and Corn Ethanol Infrastructure.

Anthropogenic discharge of excess phosphorus (P) to water bodies and increasingly stringent discharge limits have fostered interest in quantifying opportunities for P recovery and reuse. To date, geospatial estimates of P recovery potential in the United States (US) have used human and livestock population data, which do not capture the engineering constraints of P removal from centralized water resource recovery facilities (WRRFs) and corn ethanol biorefineries where P is concentrated in coproduct animal feeds. Here, renewable P (rP) estimates from plant-wide process models were used to create a geospatial inventory of recovery potential for centralized WRRFs and biorefineries, revealing that individual corn ethanol biorefineries can generate on average 3 orders of magnitude more rP than WRRFs per site, and all corn ethanol biorefineries can generate nearly double the total rP of WRRFs across the US. The Midwestern states that make up the Corn Belt have the largest potential for P recovery and reuse from both corn biorefineries and WRRFs with a high degree of co-location with agricultural P consumption, indicating the untapped potential for a circular P economy in this globally significant grain-producing region.

Defining Nutrient Colocation Typologies for Human-Derived Supply and Crop Demand To Advance Resource Recovery.

Resource recovery from human excreta can advance circular economies while improving access to sanitation and renewable agricultural inputs. While national projections of nutrient recovery potential provide motivation for resource recovery sanitation, elucidating generalizable strategies for sustainable implementation requires a deeper understanding of country-specific overlap between supply and demand. For 107 countries, we analyze the colocation of human-derived nutrients (in urine) and crop demands for nitrogen, phosphorus, and potassium. To characterize colocation patterns, we fit data for each country to a generalized logistic function. Using fitted logistic curve parameters, three typologies were identified: (i) dislocated nutrient supply and demand resulting from high density agriculture (with low population density) and nutrient islands (e.g., dense cities) motivating nutrient concentration and transport; (ii) colocated nutrient supply and demand enabling local reuse; and (iii) diverse nutrient supply-demand proximities, with countries spanning the continuum between (i) and (ii). Finally, we explored connections between these typologies and country-specific contextual characteristics via principal component analysis and found that the Human Development Index was clustered by typology. By providing a generalizable, quantitative framework for characterizing the colocation of human-derived nutrient supply and agricultural nutrient demand, these typologies can advance resource recovery by informing resource management strategies, policy, and investment.

Phosphorus fractionation and protein content control chemical phosphorus removal from corn biorefinery streams.

The economic viability of corn biorefineries depends heavily on the sale of coproducts as animal feeds, but elevated phosphorus (P) contents can exacerbate manure management issues. Phosphorus removal from light steep water and thin stillage, two concentrated in-process aqueous streams at wet milling and dry-grind corn biorefineries, could simultaneously generate concentrated fertilizer and low-P animal feeds, but little is known regarding how differences in stream composition affect removal. To address this data gap, we show that the solubility of P in light steep filtrate (LSF) and thin stillage filtrate (TSF) exhibits distinct sensitivity to calcium (Ca) and base addition due to differences in P fractionation and protein abundance. In LSF, P was primarily organic, and near-complete removal of P (96%) was observed at pH 8 and a Ca/total P (TP) ratio of 2. In TSF, TP removal was lower (81%), and there was more equal distribution of organic and orthophosphate, indicating that the Ca requirements of inorganic P precipitation were a limiting factor. The C/H/N ratio, elemental characterization, and crude protein analysis of the precipitated solids indicated that coprecipitation of amorphous solids containing Ca, Mg, and K with soluble proteins facilitated removal of P, particularly in LSF. Although the removal mechanisms and solubility limits differed, these results highlighted the magnitude (40-70 mM) and efficacy (80-96%) of P recovery from two biorefinery streams.

Toward a Regional Phosphorus (Re)cycle in the US Midwest.

Redirecting anthropogenic waste phosphorus (P) flows from receiving water bodies to high P demand agricultural fields requires a resource management approach that integrates biogeochemistry, agronomy, engineering, and economics. In the US Midwest, agricultural reuse of P recovered from spatially colocated waste streams stands to reduce point-source P discharges, meet agricultural P needs, and-depending on the speciation of recovered P-mitigate P losses from agriculture. However, the speciation of P recovered from waste streams via its chemical transformation-referred to here as recovered P (rP) differs markedly based on waste stream composition and recovery method, which can further interact with soil and crop characteristics of agricultural sinks. The solubility of rP presents key tensions between engineered P recovery and agronomic reuse because it defines both the ability to remove organic and inorganic P from aqueous streams and the crop availability of rP. The potential of rP generation and composition differs greatly among animal, municipal, and grain milling waste streams due to the aqueous speciation of P and presence of coprecipitants. Two example rP forms, phytin and struvite, engage in distinct biogeochemical processes on addition to soils that ultimately influence crop uptake and potential losses of rP. These processes also influence the fate of nitrogen (N) embodied in rP. The economics of rP generation and reuse will determine if and which rP are produced. Matching rP species to appropriate agricultural systems is critical to develop sustainable and financially viable regional exchanges of rP from wastewater treatment to agricultural end users.

Elucidating the impacts of initial supersaturation and seed crystal loading on struvite precipitation kinetics, fines production, and crystal growth.

To reduce intra-plant nutrient cycling, and recover phosphorus (P) fertilizers from nutrient-rich sidestreams, wastewater utilities increasingly elect to employ struvite precipitation processes without a clear understanding of the inherent tradeoffs associated with specific design and operating decisions. Specifically, the impact of reactor conditions on struvite crystallization rate, and distribution between formation of fines particles and secondary growth onto large diameter seed crystals represent critical knowledge gaps limiting the predictive capabilities of existing process models. In this work, the relative impacts of initial supersaturation (Si), and seed loading, on P removal kinetics, and struvite solids distribution were investigated. In experiments conducted at different levels of initial supersaturation (1.7-2.4) and seed loading (0-25 g L-1), struvite fines represented the majority of phosphate solids formed in 10 of 12 conditions. While total P removal was dependent on Si, and primarily attributed to formation of fines, the concentration of struvite seed granules had a significant impact on the rate of P removal. Struvite seed granules increased the rate of precipitation by reducing induction time of primary nucleation of struvite fines. Secondary crystal growth represented the majority of struvite solids formed at high seed loading and low Si, but presented the tradeoff of low total removal and low rate of removal. To convey the significance of these findings on process modeling, we show how a prominent kinetic model with a first-order dependency on solid struvite concentration over-predicts P removal rate when total mass is dominated by large diameter seeds (0.9 mm). This works reveals the critical role of struvite fines in P removal, and highlights the need to account for their production and kinetic importance in struvite process design and operation.

Carotenoids, vitamin A, vitamin C, vitamin E, and folate and risk of self-reported hearing loss in women.

BACKGROUND: Higher intake of certain vitamins may protect against cochlear damage from vascular compromise and oxidative stress, thereby reducing risk of acquired hearing loss, but data are limited. OBJECTIVE: We prospectively examined the relation between carotenoids, vitamin A, vitamin C, vitamin E, and folate intake and risk of self-reported hearing loss in women. DESIGN: This prospective cohort study followed 65,521 women in the Nurses' Health Study II from 1991 to 2009. Baseline and updated information obtained from validated biennial questionnaires was used in Cox proportional hazards regression models to examine independent associations between nutrient intake and self-reported hearing loss. RESULTS: After 1,084,598 person-years of follow-up, 12,789 cases of incident hearing loss were reported. After multivariable adjustment, we observed modest but statistically significant inverse associations between higher intake of ß-carotene and ß-cryptoxanthin and risk of hearing loss. In comparison with women in the lowest quintile of intake, the multivariable-adjusted RR of hearing loss among women in the highest quintile was 0.88 (95% CI: 0.81, 0.94; P-trend < 0.001) for ß-carotene and 0.90 (95% CI: 0.84, 0.96; P-trend < 0.001) for ß-cryptoxanthin. In comparison with women with folate intake 200-399 µg/d, very low folate intake (<200 µg/d) was associated with higher risk (RR: 1.19; 95% CI: 1.01, 1.41), and higher intake tended to be associated with lower risk (P-trend = 0.04). No significant associations were observed for intakes of other carotenoids or vitamin A. Higher vitamin C intake was associated with higher risk; in comparison with women with intake <75 mg/d, the RR among women with vitamin C intake ≥1000 mg/d (mainly supplemental) was 1.22 (95% CI: 1.06, 1.42; P-trend = 0.02). There was no significant trend between intake of vitamin E intake and risk. CONCLUSION: Higher intakes of ß-carotene, ß-cryptoxanthin, and folate, whether total or from diet, are associated with lower risk of hearing loss, whereas higher vitamin C intake is associated with higher risk.

Fish and fatty acid consumption and the risk of hearing loss in women.

BACKGROUND: Acquired hearing loss is common and often disabling, yet limited prospective data exist on potentially modifiable risk factors. Evidence suggests that higher intake of fish and long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs) may be associated with a lower risk of hearing loss, but prospective information on these relations is limited. OBJECTIVE: We prospectively examined the independent associations between consumption of total and specific types of fish, long-chain omega-3 PUFAs, and self-reported hearing loss in women. DESIGN: Data were from the Nurses' Health Study II, a prospective cohort study. The independent associations between consumption of fish and long-chain omega-3 PUFAs and self-reported hearing loss were examined in 65,215 women followed from 1991 to 2009. Baseline and updated information was obtained from validated biennial questionnaires. Cox proportional hazards regression models were used to estimate multivariable-adjusted RRs and 95% CIs. RESULTS: After 1,038,093 person-years of follow-up, 11,606 cases of incident hearing loss were reported. Consumption of 2 or more servings of fish per week was associated with a lower risk of hearing loss. In comparison with women who rarely consumed fish (<1 serving/mo), the multivariable-adjusted RR for hearing loss among women who consumed 2-4 servings of fish per week was 0.80 (95% CI: 0.74, 0.88) (P-trend < 0.001). When examined individually, higher consumption of each specific fish type was inversely associated with risk (P-trend ≤ 0.04). Higher intake of long-chain omega-3 PUFAs was also inversely associated with risk of hearing loss. In comparison with women in the lowest quintile of intake of long-chain omega-3 PUFAs, the multivariable-adjusted RR for hearing loss among women in the highest quintile was 0.85 (95% CI: 0.80, 0.91) and among women in the highest decile was 0.78 (95% CI: 0.72, 0.85) (P-trend < 0.001). CONCLUSION: Regular fish consumption and higher intake of long-chain omega-3 PUFAs are associated with lower risk of hearing loss in women.

Electrochemical struvite precipitation from digestate with a fluidized bed cathode microbial electrolysis cell.

Microbial electrolysis cells (MECs) can be used to simultaneously convert wastewater organics to hydrogen and precipitate struvite, but scale formation at the cathode surface can block catalytic active sites and limit extended operation. To promote bulk phase struvite precipitation and minimize cathode scaling, a two-chamber MEC was designed with a fluidized bed to produce suspended particles and inhibit scale formation on the cathode surface. MEC operation elevated the cathode pH to between 8.3 and 8.7 under continuous flow conditions. Soluble phosphorus removal using digester effluent ranged from 70 to 85% with current generation, compared to 10-20% for the control (open circuit conditions). At low current densities (≤2 mA/m(2)), scouring of the cathode by fluidized particles prevented scale accumulation over a period of 8 days. There was nearly identical removal of soluble phosphorus and magnesium from solution, and an equimolar composition in the collected solids, supporting phosphorus removal by struvite formation. At an applied voltage of 1.0 V, energy consumption from the power supply and pumping (0.2 Wh/L, 7.5 Wh/g-P) was significantly less than that needed by other struvite formation methods based on pH adjustment such as aeration and NaOH addition. In the anode chamber, current generation led to COD oxidation (1.1-2.1 g-COD/L-d) and ammonium removal (7-12 mM) from digestate amended with 1 g/L of sodium acetate. These results indicate that a fluidized bed cathode MEC is a promising method of sustainable electrochemical nutrient and energy recovery method for nutrient rich wastewaters.

Free choice of healthcare providers in the Netherlands is both a goal in itself and a precondition: modelling the policy assumptions underlying the promotion of patient choice through documentary analysis and interviews.

BACKGROUND: In the Netherlands in 2006, a health insurance system reform took place in which regulated competition between insurers and providers is key. In this context, the government placed greater emphasis on patients being able to choose health insurers and providers as a precondition for competition. Patient choice became an instrument instead of solely a goal in itself. In the current study, we investigated the concept of 'patient choice' of healthcare providers, as postulated in the supporting documentation for this reform, because we wanted to try to understand the assumptions policy makers had regarding patient choice of healthcare providers. METHODS: We searched policy documents for assumptions made by policy makers about patient choice of healthcare providers that underlie the health insurance system reform. Additionally, we held interviews with people who were involved in or closely followed the reform. RESULTS: Our study shows that the government paid much more attention to the instrumental goal of patient choice. Patients are assumed to be able to choose a provider rationally if a number of conditions are satisfied, e.g. the availability of enough comparative information. To help ensure those conditions were met, the Dutch government and other parties implemented a variety of supporting instruments. CONCLUSIONS: Various instruments have been put in place to ensure that patients can act as consumers on the healthcare market. Much less attention has been paid to the willingness and ability of patients to choose, i.e. choice as a value. There was also relatively little attention paid to the consequences on equity of outcomes if some patient groups are less inclined or able to choose actively.

Fibrous dysplasia of bone and McCune-Albright syndrome.

Fibrous dysplasia of bone is a genetic, non-inheritable disease, characterized by bone pain, bone deformities and fracture, involving one or several bones. It is caused by mis-sense mutations occurring post-zygotically in the gene coding for the alpha-subunit of the stimulatory G-protein, Gs, in the guanine nucleotide binding, alpha stimulating (GNAS) complex locus in chromosome 20q13. This mutation results in osteoblastic differentiation defects, and bone resorption is often increased. The bone lesions may be associated with endocrine dysfunctions and café-au-lait spots; this is known as McCune-Albright syndrome. Patients with polyostotic fibrous dysplasia often have renal phosphate wasting. The disease, however, has a wide clinical spectrum, so many patients are asymptomatic. Diagnosis relies on radiographs and pathology. Bisphosphonates have been used in the treatment of fibrous dysplasia to relieve bone pain and improve lytic lesions, but they are still under clinical evaluation. Calcium, vitamin D and phosphorus supplements may be useful in some patients. Surgery is also helpful to prevent and treat fracture and deformities.

Respiratory countermaneuvers in autonomic failure.

BACKGROUND: Selective increase of inspiratory impedance augments blood pressure in healthy subjects through activation of the respiratory pump. We studied the efficacy of respiratory maneuvers to reduce orthostatic hypotension in autonomic failure. METHODS: Mean arterial pressure (MAP) after standing up was recorded in 10 patients in five conditions: normal standing, leg muscle tensing, inspiratory pursed lips breathing, inspiratory sniffing, and a device causing inspiratory obstruction. RESULTS: The maneuvers caused significant differences in standing MAP. Inspiratory obstruction and leg muscle tensing increased MAP to a comparable degree. The effect of inspiratory pursed lips breathing and inspiratory sniffing depended on concomitant hyperventilation. CONCLUSION: Respiratory maneuvers reduce orthostatic hypotension in autonomic failure through activation of the respiratory pump, provided hyperventilation is avoided.

Public trust in health care: a performance indicator?

PURPOSE: If public trust in health care is to be used as a performance indicator for health care systems, its measurement has to be sensitive to changes in the health care system. For this purpose, this study has monitored public trust in health care in The Netherlands over an eight-year period, from 1997 to 2004. The study expected to find a decrease in public trust, with a low point in 2002. DESIGN/METHODOLOGY/APPROACH: Since 1997, public trust in health care was measured through postal questionnaires to the "health care consumer panel". This panel consists of approximately 1500 households and forms a representative sample of the Dutch population. FINDINGS: Trust in health care and trust in hospitals did not show any significant trend. Trust in medical specialists displayed an upward trend. Trust in future health care, trust in five out of six dimensions of health care and trust in general practitioners actually did show a decrease. However, only for trust in macro level policies and trust in professional expertise this trend continued. For the remaining trust objects, after 1999 or 2000, an upward trend set in. RESEARCH IMPLICATIONS/LIMITATIONS: No support was found for our overall assumption. Explanations for the fact that trust did increase after 1999 or 2000 are difficult to find. On the basis of these findings the study questions whether the measure of public trust is sensitive enough to provide information on the performance of the health care system. ORIGINALITY/VALUE: The aim of this research is to study public trust in health care on its abilities to be used as a performance indicator for health care systems.

Comparison of Natuphos and Phyzyme as phytase sources for commercial layers fed corn-soy diet.

The objective of this experiment was to compare the effects of 2 sources of phytase on performance of commercial Leghorns fed corn-soy diets. Seven diets were fed to Hy-line W-36 hens (n = 840; 8 replicates of 15 hens per treatment) from 21 to 33 wk of age. The treatments consisted of a control diet containing 0.38% nonphytate P (NPP) and a 2 x 3 factorial arrangement of 2 dietary NPP concentrations (0.11 and 0.26%) with 2 phytase sources [Natuphos (BASF, Mt. Olive, NJ) and Phyzyme (Danisco Animal Nutrition, Carol Stream, IL)] and without phytase. Dietary NPP had significant effects on feed intake, NPP intake, total P intake, egg production, egg weight, egg mass, egg specific gravity, and excreta P. The addition of Phyzyme or Natuphos significantly increased egg production and egg mass of hens fed the P-deficient diet (0.11% NPP) to levels that were similar to hens fed the control diet containing 0.38% NPP. Feed intake of hens fed the diets supplemented with Phyzyme or Natuphos was significantly less than that of hens fed the control diet containing 0.38% NPP. Phyzyme or Natuphos supplementation in the diets containing 0.11% NPP had significantly reduced excreta P of the control diet (approximately 58 and 54%, respectively) with no adverse effect on egg production and egg mass. There were no significant differences in feed intake, NPP intake, total P intake, egg production, egg weight, egg mass, feed conversion, egg specific gravity, mortality, BW, and excreta P between the diets supplemented with Natuphos and the diets supplemented with Phyzyme. In conclusion, Phyzyme had the same positive effects on performance of commercial Leghorns fed corn-soy diets as Natuphos.

Medical therapy in adults with fibrous dysplasia of bone.

UNLABELLED: In open studies, bisphosphonate therapy (pamidronate, alendronate) reduced bone pain associated with fibrous dysplasia of bone and was associated to some radiological improvement. Calcium, vitamin D, and phosphorus supplements may be useful in patients with deficiency. We are awaiting results from controlled trials testing bisphosphonates. INTRODUCTION: Fibrous dysplasia of bone (FD), a rare disease caused by osteoblastic lineage differentiation defects, is associated with bone pain, fracture, and bone deformity, but few therapeutic options are available. MATERIALS AND METHODS: We reviewed published data on the treatment of FD with bisphosphonates (pamidronate, alendronate), calcium, vitamin D, and phosphorus. We also present new results on FD therapy with a more potent bisphosphonate, zoledronic acid, given intravenously at the dose of 4 mg every 6 months. RESULTS: Pamidronate therapy, given intravenously every 6 months at a dose of 180 mg in adults, relieved bone pain, decreased bone resorption, and improved the radiological aspect (filling of lytic lesions and/or thickening of cortices) in approximately 50% of patients. BMD in affected sites was also significantly increased after pamidronate treatment. Those results have been obtained only in open studies, without controls, by several research groups. In a series of nine patients on long-term pamidronate treatment, but resisting to this medication and switched to intravenous zoledronic acid, no substantial improvement was observed. There is some biological rationale supporting the use of calcium and vitamin D in patients with deficiency to improve FD lesions by limiting secondary hyperparathyroidism. Phosphorus supplementation may prevent mineralization defects in those patients who have both FD and renal phosphate wasting. However, we are lacking clinical evidence for the efficacy of such supplements. CONCLUSIONS: Bisphosphonate treatment reduces increased osteoclastic activity in FD and probably improves bone pain, but their use should be better studied in randomized controlled trials.

Pediatric cholesteatoma: canal wall window alternative to canal wall down mastoidectomy.

OBJECTIVE: A previous pilot series described a hybrid mastoidectomy technique, canal wall window (CWW), which substituted for the canal wall down (CWD) procedure and involved slitting the posterior canal wall. The current, larger series compares the results of the CWW procedure with conventional surgical techniques. STUDY DESIGN: Retrospective analysis of 78 pediatric ears. SETTING: Academic tertiary referral center. PATIENTS: The mean patient age was 13.5 years. MAIN OUTCOME MEASURE(S): The data analyzed included ears later requiring conversion from CWW to CWD, dry/moist ear results, recidivation determined by two separate methods, and audiometric data statistically analyzed using independent-samples analysis (unpaired, two-tailed Student's t test). RESULTS: First, of 42 CWW ear procedures, 6 (14%) later required conversion to CWD. Second, dry ear results were as follows: for CWW, 94%; for CWD, 92%; and for CWU (canal wall up), 90%. Third, recidivation determined at 1 year (standard rate) was, for CWW, 19.5%; for CWD, 0%; and for CWU, 7.7%; the at-risk calculation rate was, for CWW, 27%; for CWD, 0%; and for CWU, 8.3%. The 6-year recidivation rate for all three surgical techniques was 0%. 4). The mean preoperative-to-postoperative four-tone air-bone gap change was, for CWW, from 29.7 to 26.4 dB; for CWD, from 32.9 to 39.0 dB; and for CWU, from 21.0 to 25.2 dB (postoperative CWW to CWD, p < 0.005). A postoperative air-bone gap result of 0 to 20 dB was achieved as follows: with CWW, in 13 of 36 ears; with CWD, in 2 of 14 ears; and with CWU, in 9 of 22 ears. CONCLUSION: Frequently, a CWW procedure can be substituted for a traditional CWD procedure. In the extended series, the CWW technique continued to provide hearing results similar to CWU rather than to CWD procedures in a young population who will bear the surgical outcome for many decades.

Role for interleukin 1alpha in the inhibition of chondrogenesis in autologous implants using polyglycolic acid-polylactic acid scaffolds.

Significant challenges remain in generating tissue-engineered cartilage in immunocompetent animals. Scaffold materials such as polyglycolic acid lead to significant inflammatory reactions, inhibiting homogeneous matrix synthesis. This study examined the generation of tissue-engineered cartilage, using a polyglycolic acid-polylactic acid copolymer (Ethisorb; Ethicon, Norderstedt, Germany) in an autologous immunocompetent pig model. The goals of this study were to determine the role of interleukin 1alpha (IL-1alpha) in this system and to assess the effect of serum treatment on tissue generation. Porcine auricular chondrocytes were seeded onto Ethisorb disks cultured for 1 week in medium supplemented with either fetal bovine serum or serum-free insulin-transferrin-selenium supplement. Specimens were implanted autogenously in pigs with unseeded scaffolds as controls. After 1, 4, or 8 weeks, six specimens from each group were explanted and analyzed histologically (hematoxylin and eosin, safranin O, trichrome, and Verhoeff's staining) and biochemically (glycosaminoglycan content). The presence and distribution of IL-1alpha were assessed by immunohistochemistry. Histology revealed acute inflammation surrounding degrading scaffold. Cartilage formation was observed as early as 1 week after implantation and continued to increase with time; however, homogeneous matrix synthesis was not present in any of the specimens. Strong IL-1alpha expression was detected in chondrocytes at the implant periphery and in cells in the vicinity of degrading polymer. Histologically there was no significant difference between the experimental groups with respect to the amount of matrix synthesis or inflammatory infiltration. The glycosaminoglycan content was significantly higher in the serum-free group. These results suggest that inflammatory reactions against scaffold materials and serum components lead to the production of cytokines such as IL-1alpha that may inhibit cartilage tissue formation in autologous transplant models.