Optimal dietary therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Current dietary therapy for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency consists of fasting avoidance, and limiting long-chain fatty acid (LCFA) intake. This study reports the relationship of dietary intake and metabolic control as measured by plasma acylcarnitine and organic acid profiles in 10 children with LCHAD or TFP deficiency followed for 1 year. Subjects consumed an average of 11% of caloric intake as dietary LCFA, 11% as MCT, 12% as protein, and 66% as carbohydrate. Plasma levels of hydroxypalmitoleic acid, hydroxyoleic, and hydroxylinoleic carnitine esters positively correlated with total LCFA intake and negatively correlated with MCT intake suggesting that as dietary intake of LCFA decreases and MCT intake increases, there is a corresponding decrease in plasma hydroxyacylcarnitines. There was no correlation between plasma acylcarnitines and level of carnitine supplementation. Dietary intake of fat-soluble vitamins E and K was deficient. Dietary intake and plasma levels of essential fatty acids, linoleic and linolenic acid, were deficient. On this dietary regimen, the majority of subjects were healthy with no episodes of metabolic decompensation. Our data suggest that an LCHAD or TFP-deficient patient should adhere to a diet providing age-appropriate protein and limited LCFA intake (10% of total energy) while providing 10-20% of energy as MCT and a daily multi-vitamin and mineral (MVM) supplement that includes all of the fat-soluble vitamins. The diet should be supplemented with vegetable oils as part of the 10% total LCFA intake to provide essential fatty acids.     

Assessing Diet Quality of Indigenous Food Systems in Three Geographically Distinct Solomon Islands Sites (Melanesia,Pacific Islands)

Indigenous Solomon Islanders, like many living in Pacific Small Island Developing States (PSIDS), are currently experiencing the global syndemic—the combined threat of obesity, undernutrition, and climate change. This mixed-method study aimed to assess nutrition transitions and diet quality by comparing three geographically unique rural and urban indigenous Solomon Islands populations. Participants in rural areas sourced more energy from wild and cultivated foods; consumed a wider diversity of foods; were more likely to meet WHO recommendations of >400 g of non-starchy fruits and vegetables daily; were more physically active; and had significantly lower body fat, waist circumference, and body mass index (BMI) when compared to urban populations. Urban populations were found to have a reduced ability to self-cultivate agri-food products or collect wild foods, and therefore consumed more ultra-processed foods (classified as NOVA 4) and takeout foods, and overall had less diverse diets compared to rural populations. Clear opportunities to leverage traditional knowledge and improve the cultivation and consumption of underutilized species can assist in building more sustainable and resilient food systems while ensuring that indigenous knowledge and cultural preferences are respected.     

Assessing clinical significance: proposed extensions to method

Jacobson, Follette, and Revenstorf's (1984) proposal for assessing clinical significance provides a needed convention for psychotherapy outcome research. Several limitations that exists in this method (Jacobson & Revenstorf, 1988) are addressed in this paper and extensions are proposed. Specifically, limitations regarding the operationalization of the underlying social validation methodology in the derivation of normative samples and the resultant standards they set are discussed. Extensions and guidelines are proposed for specifying normative samples, determining the distinctness of these samples, and expanding procedures to accommodate multiple samples. This paper initially assumes a psychometric perspective and presents extensions, based on the Symptom Checklist 90-R. Then it shifts to a clinician perspective and applies reliable change estimates and cutoff scores to actual outcome data by analyzing the progress of four patients during and after therapy. The overall merit and utility of extensions to clinical significance are then discussed.     

Clinically significant change: practical indicators for evaluating psychotherapy outcome

Developing procedures to evaluate the clinical significance of psychotherapy outcome is imperative. We see social validation as the most promising, viable methodology in this endeavor. Several concerns have been raised, however, about our proposed extensions. In this article, we illuminate and reassert the importance of generating and using multiple normative samples, and the utility of our statistical extensions. We address the limitations of procedural error and skewed sample distributions. Finally we see our commentary as a call for extensive study of the relationship between scores on standard outcome instruments and client's life functioning. We trust our commentary will continue to stimulate healthy dialogue on this crucial topic.     

Studies of serum C-reactive protein in systemic lupus erythematosus

OBJECTIVE: To examine the relationship of serum C-reactive protein (CRP) levels to other indicators of disease activity during the course of systemic lupus erythematosus (SLE). METHODS: In 124 patients serum CRP was measured retrospectively by ELISA and in some instances by radial immunodiffusion. Serum CRP levels were compared to laboratory, clinical, and radiographic assessments of disease activity. In many patients, serial CRP levels were measured over months or years to determine whether elevations of serum CRP reflected apparent changes in other disease activity variables. CRP was also measured in lyophilized aliquots of 24 h urine samples from SLE patients and controls with other renal disorders. Parallel determinations of interleukin 6 (IL-6) were made by ELISA in healthy controls and SLE patients. RESULTS: Of the 124 SLE patients studied, most showed elevations in serum CRP levels in the course of their disease. No inverse or direct correlation was noted between serum CRP and levels of nucleosome antigen or serum IgM or IgG anti-DNA antibody. In patients with renal involvement and proteinuria, CRP was often detected in 24-h urine samples. A strong correlation (p < 0.001) was noted between CRP and IL-6 levels in healthy subjects, but no correlation was recorded between serum CRP and IL-6 in SLE. CONCLUSION: Contrary to previous reports, most patients with SLE in our study showed elevations of serum CRP during the course of their illness, and extremely high serum CRP was recorded in some patients. CRP was also found in concentrated urine samples from patients with renal involvement and often paralleled elevated serum levels. In patients, no correlation was seen between CRP serum levels and serum IL-6, whereas a strong correlation between CRP level and IL-6 was recorded in healthy subjects.     

Evidence for covalent binding of acyl glucuronides to serum albumin via an imine mechanism as revealed by tandem mass spectrometry.

Acyl glucuronide metabolites of bilirubin and many drugs can react with serum albumin in vivo to form covalent adducts. Such adducts may be responsible for some toxic effects of carboxylic nonsteroidal antiinflammatory agents. The mechanism of formation of the adducts and their chemical structures are unknown. In this paper we describe the use of tandem mass spectrometry to locate binding sites and elucidate the binding mechanism involved in the formation of covalent adducts from tolmetin glucuronide and albumin in vitro. Human serum albumin and excess tolmetin glucuronide were coincubated in the presence of sodium cyanoborohydride to trap imine intermediates. The total protein product was reduced, carboxymethylated, and digested with trypsin. Six tolmetin-containing peptides (indicated by absorbance at 313 nm) were isolated by high-pressure liquid chromatography and analyzed by liquid secondary-ion mass spectrometry and collision-induced dissociation, using a four-sector tandem mass spectrometer. All six peptides contained tolmetin linked covalently via a glucuronic acid to protein lysine groups. Major attachment sites on the protein were Lys-195, -199, and -525; minor sites were identified as Lys-137, -351, and -541. Our results show unambiguously that the glucuronic acid moiety of acyl glucuronides can be retained within the structure when these reactive metabolites bind covalently to proteins, and they suggest that acyl migration followed by Schiff base (imine) formation is a credible mechanism for the generation of covalent adducts in vivo.     

Coexistence of anti-RNA polymerase III and anti-U1RNP antibodies in patients with systemic lupus erythematosus: two cases without features of scleroderma

Anti-RNA polymerase III (RNAP III) antibodies are highly specific for scleroderma (SSc) and associated with diffuse SSc and renal crisis. Coexistence of anti-RNAP III and other SSc autoantibodies is rarely documented. We report three cases with coexisting anti-RNAP III and anti-U1RNP. Autoantibodies in 3829 sera from rheumatology clinics were screened by immunoprecipitation. Anti-RNAP III-positive sera were also examined by immunofluorescence and anti-RNAP III ELISA. In total, 35 anti-RNAP III-positive sera were identified by immunoprecipitation, in which three had coexisting anti-U1RNP. All three were anti-RNAP III ELISA positive. Two had anti-RNAP I dominant (vs. RNAP III) reactivity and showed strong nucleolar staining. A case with anti-U1/U2RNP (U2RNP dominant) had systemic lupus erythematosus (SLE)-SSc overlap syndrome; however, the remaining two cases had SLE without signs of SSc. All three cases of anti-RNAP III?+?U1RNP fulfilled ACR SLE criteria but none in the group with anti-RNAP III alone (p?=?0.0002). In contrast, only one case in the former group had sclerodermatous skin changes and Raynaud's phenomenon, vs. 92% with scleroderma in the latter (p?相似文献