Dietary supplement adulteration - knowledge, attitudes, and practices of California health care professionals: A cross-sectional survey study.

OBJECTIVE: To assess knowledge, attitudes, and practices surrounding dietary supplements (DS) among California health care professionals (HCPs) and assess factors contributing to the frequency with which HCPs discuss DS with patients. METHODS: In this cross-sectional study, an online questionnaire was distributed to HCPs in California from December 2021-April 2022 via professional membership email listservs. RESULTS: Among 514 HCPs, overall knowledge of DS did not vary significantly by professional group, and 90% had received little to no DS education. Pharmacists (OR = 0.328, p = 0.0001) and those with less reported DS education (OR = 0.58, p = 0.0045; OR = 0.075, p = 0.0097) had a decreased likelihood of initiating conversations about DS more frequently. Females (OR = 2.5, p < 0.0001) and those with a higher knowledge score (OR = 1.2, p = 0.0297) had an increased likelihood of initiating conversations about DS more frequently. CONCLUSIONS: HCPs acknowledge the clinical significance of DS adulteration and would benefit from additional informational resources to reduce the adverse effects associated with adulterated supplements. PRACTICE IMPLICATIONS: HCPs initiate more conversations about DS use when they are more informed and will gain from staying up to date on DS-related information to encourage more patient communication.

Short term clinical and echocardiography outcomes of pericardiectomy in constrictive pericarditis.

Introduction: Tuberculous pericarditis continues to be a leading cause of chronic constrictive pericarditis (CCP) in developing countries. Echocardiography plays a key role in the assessment and diagnosis. Methods: Twelve patients who underwent pericardiectomy for CCP in last 18 months of the study period were subjected to clinical and New York Heart Association (NYHA) functional class assessment along with comprehensive echocardiographic evaluation. The data were compared with their preprocedural status. Results: Significant reduction was noted in the incidence of inferior vena cava (IVC) congestion(P < 0.001) and mean left atrial (LA) size from 43.75 ± 4.43 mm to 31.58 ± 3.03 mm (P < 0.001), post pericardiectomy.Respiratory variation of 34.17 ± 8.76 % in the mitral E velocity was significantly reduced to 17 ± 3.69 % (P < 0.001) after surgery. Similarly, respiratory variation in tricuspid E velocities showed significant reduction from 62.17 ± 13.16 % to 32.58 ± 4.7 % (P < 0.001).Prior to pericardiectomy, medial e' and lateral e' mitral annular velocities was 15.5±1.24 cm/sec and13.08 ± 1.08 cm/sec, respectively. Following surgery, the medial e' and lateral e' was 12.5±1.17 cm/sec(P = 0.001) and 15.42±1.83 (P = 0.004), respectively. Conclusion: Echocardiography provides useful insight in pericardial constriction hemodynamics and worthwhile effects of pericardiectomy.

Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings.

Importance: Over half of adults in the United States report consuming dietary supplements. The US Food and Drug Administration (FDA) has warned of numerous dietary supplements containing undeclared, unapproved pharmaceutical ingredients. These FDA warnings have not been comprehensively analyzed for recent years. Objective: To summarize trends across adulterated (containing unapproved ingredients) dietary supplements associated with a warning released by the FDA from 2007 through 2016. Design, Setting, and Participants: In this quality improvement study, data were extracted from the FDA's Center for Drug Evaluation and Research, Tainted Products Marketed as Dietary Supplements_CDER database from 2007 through 2016. Data from each warning were recorded unless multiple warnings were issued for the same product within a 6-month period. Date, product name, company, hidden ingredient(s), product category, source of sample, and warning document type were recorded for each included warning. Data analysis was conducted from February 2017 to June 2017. Results: From 2007 through 2016, 776 adulterated dietary supplements were identified by the FDA and 146 different dietary supplement companies were implicated. Most of these products were marketed for sexual enhancement (353 [45.5%]), weight loss (317 [40.9%]), or muscle building (92 [11.9%]), with 157 adulterated products (20.2%) containing more than 1 unapproved ingredient. The most common adulterants were sildenafil for sexual enhancement supplements (166 of 353 [47.0%]), sibutramine for weight loss supplements (269 of 317 [84.9%]), and synthetic steroids or steroid-like ingredients for muscle building supplements (82 of 92 [89.1%]). There were 28 products named in 2 or 3 warnings more than 6 months apart. Of these products, 19 (67.9%) were reported to contain new unapproved ingredients in the second or third warning, consistent with the assumption that the FDA found the product to be adulterated more than once. In recent years (2014-2016), 117 of 303 adulterated samples (38.6%) were identified through online sampling and 104 of 303 (34.3%) were identified through the examination of international mail shipments. Conclusions and Relevance: Active pharmaceuticals continue to be identified in dietary supplements, especially those marketed for sexual enhancement or weight loss, even after FDA warnings. The drug ingredients in these dietary supplements have the potential to cause serious adverse health effects owing to accidental misuse, overuse, or interaction with other medications, underlying health conditions, or other pharmaceuticals within the supplement.

Size and methylation mosaicism in males with Fragile X syndrome.

BACKGROUND: Size and methylation mosaicism are a common phenomenon in Fragile X syndrome (FXS). Here, the authors report a study on twelve fragile X males with atypical mosaicism, seven of whom presented with autism spectrum disorder. METHODS: A combination of Southern Blot and PCR analysis was used for CGG allele sizing and methylation. FMR1 mRNA and FMRP expression were measured by qRT-PCR and by Homogeneous Time Resolved Fluorescence methodology, respectively. RESULTS: DNA analysis showed atypical size- or methylation-mosaicism with both, full mutation and smaller (normal to premutation) alleles, as well as a combination of methylated and unmethylated alleles. Four individuals carried a deletion of the CGG repeat and portions of the flanking regions. The extent of methylation among the participants was reflected in the lower FMR1 mRNA and FMRP expression levels detected in these subjects. CONCLUSION: Decreased gene expression is likely the main contributor to the cognitive impairment observed in these subjects; although the presence of a normal allele did not appear to compensate for the presence of the full mutation, it correlated with better cognitive function in some but not all of the reported cases emphasizing the complexity of the molecular and clinical profile in FXS.

Malposition of Subclavian Venous Catheter Leading to Chest Complications.

Although Central Venous Catheter (CVC) placement is a relatively simple procedure but its insertion and maintenance are associated with significant risks. Malposition (defined as any CVC tip position outside the superior vena cava) may be associated with catheter insertion and may require immediate intervention. It may result in complications like haemothorax, pleural effusions, pneumothorax, sepsis, thrombosis and cardiac tamponade. This case report presents timely detection of the complication after placement of CVC. Everyone should be aware of the complications and monitor consistently appropriate position of catheter tips.

Reduced excitatory amino acid transporter 1 and metabotropic glutamate receptor 5 expression in the cerebellum of fragile X mental retardation gene 1 premutation carriers with fragile X-associated tremor/ataxia syndrome.

A premutation (PM) expansion (55-200 CGG) in the fragile X mental retardation gene 1 causes elevated messenger RNA and reduced fragile X mental retardation gene 1 protein. Young PM carriers can develop characteristic physical features and mild cognitive disabilities. In addition, individuals with PM, particularly male carriers, are at high risk to develop fragile X-associated tremor/ataxia syndrome (FXTAS) with aging. Human postmortem FXTAS brains show extensive white matter disease in the cerebellum and the presence of intranuclear inclusions throughout the brain, although their etiologic significance is unknown. In the current work, expression levels of the metabotropic glutamate (Glu) receptor 5 and the Glu transporter excitatory amino acid transporter 1, examined by reverse transcription polymerase chain reaction and western blot analyses, were found to be reduced in the postmortem cerebellum of PM carriers with FXTAS compared with age matched controls, with higher CGG repeat number having greater reductions in both proteins. These data suggests a dysregulation of Glu signaling in PM carriers, which would likely contribute to the development and severity of FXTAS.

CGG-repeat length threshold for FMR1 RNA pathogenesis in a cellular model for FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that affects carriers of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. The presence of elevated levels of expanded mRNA found in premutation carriers is believed to be the basis for the pathogenesis in FXTAS, but the exact mechanisms by which the mRNA causes toxicity are not known. In particular, it is not clear whether there is a threshold for a CGG-repeat number below which no cellular dysregulation occurs, or whether toxicity depends on mRNA concentration. We have developed a doxycycline-inducible episomal system that allows us to study separately the effects of CGG-repeat number and mRNA concentration (at fixed CGG-repeat length) in neuroblastoma-derived SK cells. Our findings show that there is a CGG-repeat size threshold for toxicity that lies between 62 and 95 CGG repeats. Interestingly, for repeat sizes of 95 CGG and above, there is a clear negative correlation between mRNA concentration and cell viability. Taken together, our results provide evidence for an RNA-toxicity model with primary dependence on CGG-repeat size and secondary dependence on mRNA concentration, thus formally ruling out any simple titration model that operates in the absence of either protein-binding cooperativity or some form of length-dependent RNA structural transition.

Clinical phenotypes of a juvenile sibling pair carrying the fragile X premutation.

Individuals with alleles containing 55-200 CGG repeats in the fragile X mental retardation (FMR1) gene are premutation carriers. The premutation allele has been shown to lead to a number of types of clinical involvement, including shyness, anxiety, social deficits, attention deficit hyperactivity disorder (ADHD), and executive function deficits. Some of these problems could be due to mild deficits of the fragile X protein (FMRP) and a possible developmental effect of the elevated FMR1 mRNA observed in carriers. In addition, two abnormal phenotypes specific to the premutation have been described. Primary ovarian insufficiency (FXPOI), defined by cessation of menses prior to age 40, occurs in 20% of females with the premutation. The other phenotype, fragile X-associated tremor/ataxia syndrome (FXTAS), affects some older adult premutation carriers. Premutation females typically have one expanded allele (≥55 CGG repeats) and one normal allele (≤54 CGG repeats). This study describes the cognitive, behavioral, and molecular profile of a female with two alleles in the premutation range (60 and 67 CGG repeats) in comparison to her brother with a similar premutation size (65 CGG repeats). Both exhibited high IQ scores, anxiety, and some physical features associated with fragile X syndrome. This comparison allows us to examine the effect of the premutation in this male-female pair while controlling for environmental and background genetic factors.

A novel family of C. elegans snRNPs contains proteins associated with trans-splicing.

In many Caenorhabditis elegans pre-mRNAs, the RNA sequence between the 5' cap and the first 3' splice site is replaced by trans-splicing a short spliced leader (SL) from the Sm snRNP, SL1. C. elegans also utilizes a similar Sm snRNP, SL2, to trans-splice at sites between genes in polycistronic pre-mRNAs from operons. How do SL1 and SL2 snRNPs function in different contexts? Here we show that the SL1 snRNP contains a complex of SL75p and SL21p, which are homologs of novel proteins previously reported in the Ascaris SL snRNP. Interestingly, we show that the SL2 snRNP does not contain these proteins. However, SL75p and SL26p, a paralog of SL21p, are components of another Sm snRNP that contains a novel snRNA species, Sm Y. Knockdown of SL75p is lethal. However, knockdown of either SL21p or SL26p alone leads to cold-sensitive sterility, whereas knockdown of both SL21p and SL26p is lethal. This suggests that these two proteins have overlapping functions even though they are associated with different classes of snRNP. These phenotypic relationships, along with the association of SL26p with SL75p, imply that, like the SL1 RNA/Sm/SL75p/SL21p complex, the Sm Y/Sm/SL75p/SL26p complex is associated with trans-splicing.