Bone health outcomes in post-lung transplant patients with cystic fibrosis.

BACKGROUND: Osteoporosis is a common comorbidity in patients with cystic fibrosis (CF). Although lung transplantation (LTx) improves quality of life of CF patients, there is little research examining long-term bone health outcomes following LTx in these patients. METHODS: Data were collected on 59 patients who underwent LTx between 2006 and 2019, including 30 with CF and 29 without CF. We compared baseline characteristics, long-term bone mineral density (BMD) trends, and fracture incidence between the two patient populations, and examined factors associated with post-LTx fractures in CF patients. RESULTS: Compared with non-CF patients, patients with CF were younger, had lower body mass index, and lower baseline BMD Z-scores at the lumbar spine, femoral neck, and total hip (all p<0.001). BMD at all sites declined in both groups in the first year post-LTx. In subsequent years, CF patients exhibited better BMD recovery relative to pre-transplantation, but continued to have lower BMD post-LTx. Post-transplant fractures occurred in 30% and 34% of CF and non-CF patients, respectively. CF patients who developed fractures after LTx had significantly lower BMD and lower pre-transplantation percent predicted forced expiratory volume in one second (FEV1%). CONCLUSIONS: Although CF patients exhibit better BMD recovery following LTx compared to their non-CF counterparts, CF patients start with significantly lower pre-LTx BMD and experience a similarly high rate of post-LTx fractures. These findings highlight the unique contribution of the CF disease process to bone health, as well as a clear need for better prevention and treatment of osteoporosis in CF patients before and after LTx.

Environmental management in Ramsar designated wetland areas in Vietnam: studies from U Minh Thuong and Tram Chim national parks (Mekong Delta).

This study investigated the possibility of using remotely sensed data and field surveys for understanding the environmental management practices in two Ramsar sites - U Minh Thong and Tram Chim national parks - in the Vietnamese Mekong Delta. Enhanced agriculture, infrastructure development, changes in hydrological regime, forest fires, and natural resources exploitation are the key variables that caused the depletion of these two wetland areas. Land cover, particularly vegetation coverage, has been changed considerably during the post-war period and agriculture has been intensified in the surrounding areas of U Minh Thuong and Tram Chim wetlands. The current water management strategies in U Minh Thuong and Tram Chim were designated to ensure proper water circulation during the dry and wet seasons in a way helpful to agriculture in the buffer zones and to prevent forest fires during the dry season. It is found that the water management strategies to prevent forest fires in both the parks resulted in the accumulation of toxic agrochemicals within the park during the wet season. Both U Minh Thuong and Tram Chim wetlands are invaded by alien plant species which is threatening the natural biodiversity of the area. Proper monitoring and control of invasive species is necessary for protecting the natural biodiversity of these wetland ecosystems. Proper law enforcement and an interactive and inclusive wetland management should be practiced in order to conserve these valuable wetland ecosystems.

Tilapia Lake Virus (TiLV) from Vietnam is genetically distantly related to TiLV strains from other countries.

Tilapia Lake Virus (TiLV) is reported as a threat to tilapia aquaculture in 16 countries on four continents with outbreaks causing up to 90% mortality. This research is one of the first studies on TiLVs from Vietnam. We propagated successfully one TiLV isolate HB196-VN-2020 from a diseased tilapia sample using an E-11 cell line and evaluated its virulence in two different weights of red hybrid tilapia and three serial 10-fold diluted viral titers. Smaller fish (4.5 ± 1.98 g) were proved to be more susceptible to TiLV infection at the viral titre of 9.1 × 105 TCID50 fish-1 than larger fish (20.8 ± 7.5 g) with the mortalities of 92.5% and 12.5%, respectively. Reassortant detection analysis revealed seven potential reassortment events among 23 TiLV genomes, indicating the mixed infection of multiple TiLV isolates at the farms and the fish movement among different regions. Seven maximum likelihood phylogenetic trees based on the individual segments or the concatenated coding regions of some segments showed the genetically distant relationship of the Southern Vietnamese isolate RIA2-VN-2019 with the 21 reference isolates, and suggest the different origins of two Vietnamese TiLV isolates (RIA2-VN-2019 and HB196-VN-2020). However, additional sequences from various sampling locations and times are required to better understand the impacts of genetic diversity and reassortments on the evolution, migration and natural selection of TiLVs in Vietnam and other countries.

A Critique of Helsinki Criteria for Using Lung Fiber Levels to Determine Causation in Mesothelioma Cases.

Asbestos is a known human carcinogen and the chief known cause of mesothelioma. In 1997, a group of experts developed the Helsinki Criteria, which established criteria for attribution of mesothelioma to asbestos. The criteria include two methods for causation attribution: 1) a history of significant occupational, domestic, or environmental exposure and/or 2) pathologic evidence of exposure to asbestos. In 2014, the Helsinki Criteria were updated, and these attribution criteria were not changed. However, since the Helsinki Criteria were first released in 1997, some pathologists, cell biologists, and others have claimed that a history of exposure cannot establish causation unless the lung asbestos fiber burden exceeds "the background range for the laboratory in question to attribute mesothelioma cases to exposure to asbestos." This practice ignores the impact on fiber burden of clearance/translocation over time, which in part is why the Helsinki Criteria concluded that a history of exposure to asbestos was independently sufficient to attribute causation to asbestos. After reviewing the Helsinki Criteria, we conclude that their methodology is fatally flawed because a quantitative assessment of a background lung tissue fiber level cannot be established. The flaws of the Helsinki Criteria are both technical and substantive. The 1995 paper that served as the scientific basis for establishing background levels used inconsistent methods to determine exposures in controls and cases. In addition, historic controls cannot be used to establish background fiber levels for current cases because ambient exposures to asbestos have decreased over time and control cases pre-date current cases by decades. The use of scanning electron microscope (SEM) compounded the non-compatibility problem; the applied SEM cannot distinguish talc from anthophyllite because it cannot perform selected area electron diffraction, which is a crucial identifier in ATEM for distinguishing the difference between serpentine asbestos, amphibole asbestos, and talc.

A Review of the Talc Industry's Influence on Federal Regulation and Scientific Standards for Asbestos in Talc.

The talc industry and Food and Drug Administration (FDA) have asserted that talc has been asbestos-free since 1976 when the industry created a voluntary specification for the asbestos content of cosmetic talc. However, recent evidence reveals that cosmetic talc is not and never was asbestos-free. This narrative review examines the talc industry's role in delaying and ultimately blocking federal regulation of cosmetic talc from the 1970s to today. We review primary source material, including corporate documents released in recent litigation and FDA documents released in response to Freedom of Information Act requests. Our results indicate that the talc industry exerted considerable influence over three key areas: regulatory proceedings at the FDA; testing methods and the manipulation of test results (including undisclosed results); and press coverage and the medical literature. The talc companies' actions and FDA indifference have had a lasting effect on consumer health, including the regulation of talc by other government agencies.

Impact of age and renal function on urine chemistry in patients with calcium oxalate kidney stones.

Nephrolithiasis is associated with an increased risk of chronic kidney disease, and its incidence varies with age. However, little is known on the combined impact of aging and declining renal function on urinary risk factors for calcium oxalate stone formation. A retrospective analysis was performed on 24-h urine collections from 993 calcium oxalate stone-forming patients. We first tested for interactions between age and creatinine clearance on various urinary determinants of calcium oxalate nephrolithiasis, and then examined their separate and combined effects in univariable and multivariable analyses adjusting for demographic and biochemical covariates. We identified significant interactions between age and creatinine clearance in predicting 24-h urine pH, calcium, and citrate. In view of the small number of stone formers with low creatinine clearance, we limited further regression analyses to patients with creatinine clearance ≥ 60 mL/min. In multivariable analyses, urine citrate, oxalate, and total volume were positively correlated with age, whereas urine pH, citrate, calcium, oxalate, total volume, and RSR of calcium oxalate all significantly decreased with lower creatinine clearance. A decrease in creatinine clearance from 120 to 60 mL/min was associated with clinically significant decreases in the daily excretion rate of citrate (by 188 mg/day), calcium (by 33 mg/day), and oxalate (by 4 mg/day), and in RSR calcium oxalate (by 1.84). Age and creatinine clearance are significant and independent predictors of several urinary determinants of calcium oxalate nephrolithiasis. The impacts of aging and declining renal function should be considered during the management of calcium oxalate stone-forming patients.

GAL08, an Uncultivated Group of Acidobacteria, Is a Dominant Bacterial Clade in a Neutral Hot Spring.

GAL08 are bacteria belonging to an uncultivated phylogenetic cluster within the phylum Acidobacteria. We detected a natural population of the GAL08 clade in sediment from a pH-neutral hot spring located in British Columbia, Canada. To shed light on the abundance and genomic potential of this clade, we collected and analyzed hot spring sediment samples over a temperature range of 24.2-79.8°C. Illumina sequencing of 16S rRNA gene amplicons and qPCR using a primer set developed specifically to detect the GAL08 16S rRNA gene revealed that absolute and relative abundances of GAL08 peaked at 65°C along three temperature gradients. Analysis of sediment collected over multiple years and locations revealed that the GAL08 group was consistently a dominant clade, comprising up to 29.2% of the microbial community based on relative read abundance and up to 4.7 × 105 16S rRNA gene copy numbers per gram of sediment based on qPCR. Using a medium quality threshold, 25 single amplified genomes (SAGs) representing these bacteria were generated from samples taken at 65 and 77°C, and seven metagenome-assembled genomes (MAGs) were reconstructed from samples collected at 45-77°C. Based on average nucleotide identity (ANI), these SAGs and MAGs represented three separate species, with an estimated average genome size of 3.17 Mb and GC content of 62.8%. Phylogenetic trees constructed from 16S rRNA gene sequences and a set of 56 concatenated phylogenetic marker genes both placed the three GAL08 bacteria as a distinct subgroup of the phylum Acidobacteria, representing a candidate order (Ca. Frugalibacteriales) within the class Blastocatellia. Metabolic reconstructions from genome data predicted a heterotrophic metabolism, with potential capability for aerobic respiration, as well as incomplete denitrification and fermentation. In laboratory cultivation efforts, GAL08 counts based on qPCR declined rapidly under atmospheric levels of oxygen but increased slightly at 1% (v/v) O2, suggesting a microaerophilic lifestyle.

Uric acid stone disease: lessons from recent human physiologic studies.

PURPOSE OF REVIEW: An overly acidic urine resulting in supersaturation of urine with respect to uric acid is the major mechanism responsible for uric acid nephrolithiasis. The present review summarizes findings from recent human physiologic studies examining the pathophysiology and reversibility of low urine pH in uric acid stone formers. RECENT FINDINGS: Epidemiologic and metabolic studies have confirmed an increase in the prevalence of uric acid nephrolithiasis and reported its association with several features of the metabolic syndrome including dyslipidemia, hyperglycemia, hepatic steatosis, and greater visceral adiposity. Physiologic studies in uric acid stone formers have identified diet-independent excessive net acid excretion and concomitant reduction in urinary buffering from impaired renal ammoniagenesis as the two causes underlying the greater aciduria. Administration of the insulin sensitizer pioglitazone to uric acid stone formers reduced the acid load presented to the kidney and enhanced ammoniagenesis and ammonium excretion, resulting in significantly higher urine pH. SUMMARY: Recent human physiologic studies have identified greater acid excretion and reduced urinary buffering by ammonia as two culprits of aciduria in uric acid nephrolithiasis that can be reversed by pioglitazone, raising new questions regarding the origin of the aciduria and opening the door to pathophysiology-based treatment of uric acid stones.

Serous Ovarian Cancer Caused by Exposure to Asbestos and Fibrous Talc in Cosmetic Talc Powders-A Case Series.

OBJECTIVE: Asbestos is a known cause of ovarian cancer. We report 10 cases of serous ovarian cancer among users of Johnson & Johnson (J&J) asbestos-containing "cosmetic" talc products. METHODS: We conducted an asbestos exposure assessment during talc application and analyzed surgical tissues and talc containers for asbestos and talc. RESULTS: Talc was found in all cases and tremolite and/or anthophyllite asbestos was found in 8/10 cases. The asbestos fibers found in the "cosmetic" talc containers matched those found in tissues. We estimated inhaled asbestos dose ranged from 0.38 to 5.18 fiber years. CONCLUSION: We provide evidence that the inhaled dose of asbestos/fibrous talc from "cosmetic" talc use causes ovarian cancer. The unique combination of the types of asbestiform minerals detected in cancerous tissue and "cosmetic" talc is a fingerprint for exposure to asbestos-containing talc.

A highly-sensitive high throughput assay for dynamin's basal GTPase activity.

Clathrin-mediated endocytosis is the major pathway by which cells internalize materials from the external environment. Dynamin, a large multidomain GTPase, is a key regulator of clathrin-mediated endocytosis. It assembles at the necks of invaginated clathrin-coated pits and, through GTP hydrolysis, catalyzes scission and release of clathrin-coated vesicles from the plasma membrane. Several small molecule inhibitors of dynamin's GTPase activity, such as Dynasore and Dyngo-4a, are currently available, although their specificity has been brought into question. Previous screens for these inhibitors measured dynamin's stimulated GTPase activity due to lack of sufficient sensitivity, hence the mechanisms by which they inhibit dynamin are uncertain. We report a highly sensitive fluorescence-based assay capable of detecting dynamin's basal GTPase activity under conditions compatible with high throughput screening. Utilizing this optimized assay, we conducted a pilot screen of 8000 compounds and identified several "hits" that inhibit the basal GTPase activity of dynamin-1. Subsequent dose-response curves were used to validate the activity of these compounds. Interestingly, we found neither Dynasore nor Dyngo-4a inhibited dynamin's basal GTPase activity, although both inhibit assembly-stimulated GTPase activity. This assay provides the basis for a more extensive search for more potent and chemically desirable dynamin inhibitors.

A commentary on Roggli's "The So-Called Short-Fiber Controversy".

Dr. Victor Roggli republished a "literature review and critical analysis" of the toxicity of short fiber asbestos. His paper was originally prepared and presented at a conference of asbestos defense lawyers. His review omitted published papers that indicate that short fiber asbestos is a carcinogen. We critically review his paper.