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2.
Article in English | MEDLINE | ID: mdl-38972028

ABSTRACT

Health information technology (HIT) use among foreign-born adults of Middle Eastern and North African (MENA) descent is understudied. MENA Americans are currently categorized as "White" in the United States (US) on federal forms. Our purpose was to uncover the prevalence of HIT use among MENA immigrants compared to US- and foreign-born White adults before and after adjusting for covariates. The 2011-2018 National Health Interview Survey data (n = 161,613; ages 18 + years) were analyzed. HIT uses evaluated were searching for health information, filling prescriptions, scheduling appointments, and communicating with healthcare providers via email (last 12 months). Crude and multivariable logistic regression models were used to estimate the odds of each HIT use (searching for health information, filling prescriptions, scheduling appointments, and/or communicating with healthcare providers via email), and overall use of any HIT before and after adjustment. The most common HIT use was looking up health information (46.4% foreign-born MENA, 47.8% foreign-born White, 51.2% US-born White; p = .0079). Foreign-born adults of MENA descent had lower odds (OR = 0.64; 95% CI = 0.56-0.74) of reporting any HIT use, but no difference in reporting all HIT uses compared to US-born White adults. This is the first study to explore HIT use among MENA Americans. Results contribute to growing body of literature showing the health of MENA Americans differs from White Americans. A separate racial/ethnic identifier is needed to better capture HIT uses among populations of MENA descent.

3.
J Investig Med High Impact Case Rep ; 12: 23247096241263065, 2024.
Article in English | MEDLINE | ID: mdl-38904327

ABSTRACT

Dermatomyositis (DM) presents with inflammatory myopathy and distinct skin manifestations, often linked to specific autoantibodies. Anti-transcriptional intermediary factor-1 gamma (TIF-1γ) antibodies (Abs) are typically linked to DM in older patients and malignancy in 15% to 40% of cases. We highlight a case of a 24-year-old female who presented with weakness of proximal muscles, periorbital edema, heliotrope rash, erosions on oral mucosa, and painful scaly rash on the lower extremities. Transcriptional intermediary factor-1 gamma Abs were positive, confirming inflammatory myopathy. Treatment with steroid pulse therapy and immunoglobulin led to improvement. Evaluation for malignancy yielded unremarkable results. This case underscores the importance of recognizing and managing DM with TIF-1γ Ab positive, even in atypical demographics, and highlights the need for comprehensive malignancy evaluation.


Subject(s)
Autoantibodies , Dermatomyositis , Transcription Factors , Humans , Female , Dermatomyositis/immunology , Dermatomyositis/drug therapy , Dermatomyositis/diagnosis , Autoantibodies/blood , Young Adult , Transcription Factors/immunology
4.
Poult Sci ; 103(8): 103837, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38848630

ABSTRACT

In the first study, an in vitro culture system was developed to investigate the effects of carnosine on macrophage proinflammatory cytokine response using an established chicken macrophage cell line (CMC), gut integrity using a chicken intestinal epithelial cell line (IEC), muscle differentiation in quail muscle cells (QMCs) and primary chicken embryonic muscle cells (PMCs), and direct anti-parasitic effect against Eimeria maxima sporozoites. Cells to be tested were seeded in 24-well plates and treated with carnosine at 4 different concentrations (0.1, 1.0, and 10.0 µg). After 18 h of incubation, cells were harvested to measure gene expression of proinflammatory cytokines in CMC, tight junction (TJ) proteins in IECs, and muscle cell growth markers in QMCs and PMCs. In vivo trials were conducted to investigate the effect of dietary carnosine on disease parameters in broiler chickens challenged with E. maxima. One hundred and twenty male broiler chickens (0-day-old) were allocated into 4 treatment groups: 1) basal diet without infection (NC), 2) basal diet with E. maxima infection (PC), 3) carnosine at 10.0 mg/kg feed with PC (HCS), and 4) carnosine at 1.0 mg/kg feed with PC (LCS). All groups except NC were orally infected with E. maxima on d 14. Jejunal samples were collected for lesion scoring and jejunum gut tissues were used for transcriptomic analysis of cytokines and TJ proteins. In vitro, carnosine treatment significantly decreased IL-1ß gene expression in CMC following LPS stimulation. In vivo feeding studies showed that dietary carnosine increased BW and ADG of chickens in E. maxima-infected groups and reduced the jejunal lesion score and fecal oocyst shedding in HCS group. Jejunal IL-1ß, IL-8, and IFN-γ expression were suppressed in the HCS group compared to PC. The expression levels of claudin-1 and occludin in IECs were also increased in HCS following carnosine treatment. In conclusion, these findings highlight the beneficial effects of dietary carnosine supplementation on intestinal immune responses and gut barrier function in broiler chickens exposed to E. maxima infection.

5.
Cureus ; 16(5): e59900, 2024 May.
Article in English | MEDLINE | ID: mdl-38854227

ABSTRACT

The public health concerns from Chagas disease warrant improved cardiovascular imaging efforts, and in this report, we review a military service member presenting with electrocardiographic and cardiac magnetic resonance imaging (CMR) findings that recognized a Chagas dilated cardiomyopathy. We present an updated Chagas staging classification incorporating CMR to increase diagnosing cardiomyopathies.

6.
Br J Haematol ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38772913

ABSTRACT

The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patients with lower risk MDS in comparison to healthy controls and patients with defined autoinflammatory disorders (AIDs). The ASC/NLRP3 specks were significantly elevated in MDS patients compared to healthy controls (p < 0.001) and these levels were comparable to those found in patients with AIDs. The distribution of protein specks positive only for ASC was different to ASC/NLRP3 ones suggesting that other ASC-containing inflammasome complexes might be important in the pathogenesis of MDS. Patients with MDS-SLD had the lowest levels of interleukin (IL)-1ß, tumour necrosis factor (TNF), IL-23, IL-33, interferon (IFN) γ and IFN-α2, compared to other diagnostic categories. We also found that inflammatory cytokine TNF was positively associated with MDS progression to a more aggressive form of disease and IL-6 and IL-1ß with time to first red blood cell transfusion. Our study shows that there is value in analysing inflammatory biomarkers in MDS, but their diagnostic and prognostic utility is yet to be fully validated.

7.
Article in English | MEDLINE | ID: mdl-38649010

ABSTRACT

OBJECTIVE: To assess injured military veterans' experiences, beliefs, and daily physical and psychosocial functioning in relation to food and nutrition. DESIGN: We used a convergent mixed-methods study design and the International Classification of Functioning, Disability, and Health to operationalize the core constructs and influencing factors related to physical and psychosocial functioning, food, and nutrition. SETTING: Three Veterans Affairs polytrauma rehabilitation centers. PARTICIPANTS: Veterans who served in the United States military on or after September 11, 2001, and whose medical diagnoses met the criteria for polytrauma; at least 1 mild traumatic brain injury and at least 1 associated comorbidity (eg, posttraumatic stress disorder, chronic musculoskeletal pain, vestibular disturbances), for a total N of 43. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Themes from survey responses and semistructured interview data were pooled into core constructs and influencing factors. RESULTS: Thirty-seven veterans completed all surveys and participated in recorded interviews. Based on qualitative and quantitative data, veterans' relation to food and nutrition (ie, nutritional functioning) was found to be characterized by 5 core constructs, including food background, nutrition knowledge, meal aptitude, resource navigation, and navigation to/of food spaces. Nutritional functioning was found to be shaped by 5 influencing factors, including injuries and health conditions, ideological and cultural exposures, relations, current beliefs, and current behaviors. CONCLUSIONS: Nutritional functioning (food background, nutrition knowledge, meal aptitude, resource navigation, navigation to/of food spaces) among injured veterans is complex and shaped by multiple physical, psychosocial, economic, and cultural factors.

8.
Metallomics ; 16(5)2024 05 02.
Article in English | MEDLINE | ID: mdl-38549424

ABSTRACT

Age/stage sensitivity is considered a significant factor in toxicity assessments. Previous studies investigated cadmium (Cd) toxicosis in Caenorhabditis elegans, and a plethora of metal-responsive genes/proteins have been identified and characterized in fine detail; however, most of these studies neglected age sensitivity and stage-specific response to toxicants at the molecular level. This present study compared the transcriptome response between C. elegans L3 vs L4 larvae exposed to 20 µM Cd to explore the transcriptional hallmarks of stage sensitivity. The results showed that the transcriptome of the L3 stage, despite being exposed to Cd for a shorter period, was more affected than the L4 stage, as demonstrated by differences in transcriptional changes and magnitude of induction. Additionally, T08G5.1, a hitherto uncharacterized gene located upstream of metallothionein (mtl-2), was transcriptionally hyperresponsive to Cd exposure. Deletion of one or both metallothioneins (mtl-1 and/or mtl-2) increased T08G5.1 expression, suggesting that its expression is linked to the loss of metallothionein. The generation of an extrachromosomal transgene (PT08G5.1:: GFP) revealed that T08G5.1 is constitutively expressed in the head neurons and induced in gut cells upon Cd exposure, not unlike mtl-1 and mtl-2. The low abundance of cysteine residues in T08G5.1 suggests, however, that it may not be involved directly in Cd sequestration to limit its toxicity like metallothionein, but might be associated with a parallel pathway, possibly an oxidative stress response.


Subject(s)
Cadmium , Caenorhabditis elegans Proteins , Caenorhabditis elegans , Metallothionein , Transcriptome , Animals , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Cadmium/toxicity , Cadmium/metabolism , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Transcriptome/drug effects , Metallothionein/genetics , Metallothionein/metabolism , Larva/drug effects , Larva/genetics , Larva/metabolism
9.
BMJ Open ; 14(3): e078926, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38458809

ABSTRACT

INTRODUCTION: Glioblastoma (GBM) is the most common adult primary malignant brain tumour. The condition is incurable and, despite aggressive treatment at first presentation, almost all tumours recur after a median of 7 months. The aim of treatment at recurrence is to prolong survival and maintain health-related quality of life (HRQoL). Chemotherapy is typically employed for recurrent GBM, often using nitrosourea-based regimens. However, efficacy is limited, with reported median survivals between 5 and 9 months from recurrence. Although less commonly used in the UK, there is growing evidence that re-irradiation may produce survival outcomes at least similar to nitrosourea-based chemotherapy. However, there remains uncertainty as to the optimum approach and there is a paucity of available data, especially with regards to HRQoL. Brain Re-Irradiation Or Chemotherapy (BRIOChe) aims to assess re-irradiation, as an acceptable treatment option for recurrent IDH-wild-type GBM. METHODS AND ANALYSIS: BRIOChe is a phase II, multi-centre, open-label, randomised trial in patients with recurrent GBM. The trial uses Sargent's three-outcome design and will recruit approximately 55 participants from 10 to 15 UK radiotherapy sites, allocated (2:1) to receive re-irradiation (35 Gy in 10 daily fractions) or nitrosourea-based chemotherapy (up to six, 6-weekly cycles). The primary endpoint is overall survival rate for re-irradiation patients at 9 months. There will be no formal statistical comparison between treatment arms for the decision-making primary analysis. The chemotherapy arm will be used for calibration purposes, to collect concurrent data to aid interpretation of results. Secondary outcomes include HRQoL, dexamethasone requirement, anti-epileptic drug requirement, radiological response, treatment compliance, acute and late toxicities, progression-free survival. ETHICS AND DISSEMINATION: BRIOChe obtained ethical approval from Office for Research Ethics Committees Northern Ireland (reference no. 20/NI/0070). Final trial results will be published in peer-reviewed journals and adhere to the ICMJE guidelines. TRIAL REGISTRATION NUMBER: ISRCTN60524.


Subject(s)
Glioblastoma , Re-Irradiation , Adult , Humans , Glioblastoma/drug therapy , Glioblastoma/radiotherapy , Quality of Life , Neoplasm Recurrence, Local/drug therapy , Brain , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase II as Topic
10.
Poult Sci ; 103(5): 103628, 2024 May.
Article in English | MEDLINE | ID: mdl-38518667

ABSTRACT

This study sought to determine the relationship among broiler performance, organ development, and indicators of microbiota colonization. A total of 1,200 two-day-old male Ross 308 broiler chicks, divided among 3 cohorts of equal size, were housed in battery cages, and allotted based on body weight. On study d 11, birds were weighed, and birds with BW gain within the 10th and 90th percentiles were assigned to the Slow and Fast groups, respectively. Birds (n = 30 for each group) selected on d 11 were provided water and a corn-soybean meal-based diet ad libitum while maintained individually through study d 25 (i.e., a 14-d growth period). Parameters regarding growth performance, organ and intestine weights and lengths, and intestinal volatile fatty acid concentrations were measured. All data were analyzed by one-way ANOVA using the Mixed procedure of SAS. Fast birds exhibited greater (P < 0.001) BW gain and feed intake than slow birds, but feed conversion ratio (FCR) did not differ (P = 0.19). Additionally, Slow birds had higher (P < 0.05) relative weights (% of BW) for nearly all organs on d 11 and 25, most notably the gizzard, proventriculus, pancreas, and liver. Conversely, intestinal sections were longer (P < 0.05) in the Fast birds. Measurement of gut histomorphology did not show any notable differences between growth rate groups in terms of villi height, crypt depth, or their ratio for either time-point (P > 0.05). In terms of volatile fatty acid concentrations of luminal contents, acetate concentrations were 10.2% higher (P < 0.001) in the ileum of the Slow birds compared with Fast birds on d 25. Overall, the findings suggest that total BW gain is influenced by the development of metabolically active organs, as supported by lower weight gain in Slow birds with relatively larger organ weights and shorter intestinal lengths than their Fast counterparts. The general lack of differences in fermentation end-product concentrations in luminal contents does not rule out influence of the microbiota on growth rate of broilers, which warrants further investigation.


Subject(s)
Chickens , Fermentation , Animals , Chickens/growth & development , Chickens/physiology , Male , Gastrointestinal Microbiome/physiology , Organ Size , Diet/veterinary , Fatty Acids, Volatile/metabolism , Intestines/growth & development , Intestines/anatomy & histology , Animal Feed/analysis , Random Allocation
11.
Int J Gen Med ; 17: 305-313, 2024.
Article in English | MEDLINE | ID: mdl-38298248

ABSTRACT

Purpose: Immunotherapies have revolutionized cancer treatment; however, relatively little is known about their efficacy and toxicity in the elderly, a cohort accounting for more than half of total cancer cases. In this review, we aim to provide insight into the current knowledge base regarding the clinical utility and side effects of immunotherapies in the geriatric population as well as identify key gaps in the literature where further research is essential. Methods: We conducted a rapid critical review of available literature, focusing on studies reporting on use of immunotherapy in cancer patients aged ≥65 years. The review assessed studies that included different types of cancer, were of multiple study types (although predominantly retrospective), had different study duration, and reported different outcomes of interest. Owing to this heterogeneity, meta-analysis and a direct comparison between studies were not feasible. Results: Overall, the review findings indicate that certain malignancies have shown comparable survival rates in younger and older age groups when managed with immunotherapeutic drugs, the incidence of immunotherapy-related side effects varies only slightly by age groups, and in general there is a lack of studies on the determinants of the clinical outcomes of immunotherapy in or including geriatric patients. Conclusion: Enhanced clinical benefits along with better tolerability associated with immunotherapies make it an attractive alternative to conventional chemotherapeutic drugs, especially in elderly patients. There is currently a limited number of studies assessing the clinical outcomes of immunotherapies, particularly in the elderly. Overall, our findings reflect a need for further prospective studies focussing on geriatric patients representative of the real-life population, in order to derive a more precise understanding of the clinical utility, toxicity profile, and cost-effectiveness of immune checkpoint inhibitors in older patients with cancer.

13.
Blood Adv ; 8(9): 2172-2181, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38271621

ABSTRACT

ABSTRACT: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard-of-care for patients with advanced-stage diffuse large B-cell lymphoma (DLBCL), despite findings that patients with nongerminal center B-cell like (non-GCB) have significantly worse outcome with this regimen. We evaluated the prognostic significance of baseline risk factors, including cell of origin (COO) classified by the Hans algorithm, within an alternative chemoimmunotherapy program. At Memorial Sloan Kettering Cancer Center (MSK), 151 patients with DLBCL received sequential R-CHOP induction and (R)-ICE (rituximab, ifosfamide, carboplatin, and etoposide) consolidation. Outcome analysis based on COO was validated with a propensity score-matched cohort treated with R-CHOP from the Mayo Clinic component of the Molecular Epidemiology Resource (MER). Among the patients with GCB (n = 69) and non-GCB (n = 69) at MSK, event-free survival (EFS) of non-GCB was superior to that of GCB (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.29-0.98). Overall survival (OS) demonstrated an association in the same direction but was not statistically significant (HR, 0.68; 95% CI, 0.33-1.42). Propensity score-matched patients from MSK (n = 108) demonstrated a small attenuation in the HRs for EFS (HR, 0.57; 95% CI, 0.27-1.18) and OS (HR, 0.76; 95% CI, 0.33-1.79) and were no longer statistically significant. In contrast, the matched MER cohort (n = 108) demonstrated an EFS association (HR, 1.17; 95% CI, 0.70-1.95) and OS association (HR, 1.13; 95% CI, 0.64-2.00) in the opposite direction, but were also not statistically significant. R-CHOP induction and (R)-ICE consolidation may overcome the negative prognostic impact of the non-GCB phenotype, per the Hans algorithm, and can be preferentially selected for this population. This trial was registered at www.ClinicalTrials.gov as #NCT00039195 and #NCT00712582.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Doxorubicin , Ifosfamide , Lymphoma, Large B-Cell, Diffuse , Prednisone , Rituximab , Vincristine , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Etoposide/therapeutic use , Ifosfamide/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Prednisone/therapeutic use , Prognosis , Rituximab/therapeutic use , Treatment Outcome , Vincristine/therapeutic use , Case-Control Studies
14.
Ann Epidemiol ; 91: 23-29, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38185289

ABSTRACT

PURPOSE: Accidental death is a leading cause of mortality among military members and Veterans; however, knowledge is limited regarding time-dependent risk following deployment and if there are differences by type of accidental death. METHODS: Longitudinal cohort study (N = 860,930) of soldiers returning from Afghanistan/Iraq deployments in fiscal years 2008-2014. Accidental deaths (i.e., motor vehicle accidents [MVA], accidental overdose, other accidental deaths), were identified through 2018. Crude and age-adjusted mortality rates, rate ratios, time-dependent hazard rates and trends postdeployment were compared across demographic and military characteristics. RESULTS: During the postdeployment observation period, over one-third of deaths were accidental; most were MVA (46.0 %) or overdoses (37.9 %). Across accidental mortality categories (all, MVA, overdose), younger soldiers (18-24, 25-29) were at higher risk compared to older soldiers (40+), and females at lower risk than males. MVA death rates were highest immediately postdeployment, with a significant decreasing hazard rate over time (annual percent change [APC]: -6.5 %). Conversely, accidental overdose death rates were lowest immediately following deployment, with a significant increasing hazard rate over time (APC: 9.9 %). CONCLUSIONS: Observed divergent trends in risk for the most common types of accidental deaths provide essential information to inform prevention and intervention planning for the immediate postdeployment transition and long-term.


Subject(s)
Military Personnel , Veterans , Male , Female , Humans , Longitudinal Studies , Iraq , Afghanistan , Iraq War, 2003-2011
15.
Value Health ; 27(1): 79-94, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37879401

ABSTRACT

While the use of electronic methods to collect patient-reported outcome data in clinical trials continues to increase, it remains the case that many patient-reported outcome measures (PROMs) have originally been developed and validated on paper. Careful consideration during the move from paper PROMs to electronic format is required to preserve the integrity of the measure and ensure a "faithful migration." Relevant literature has long called out the importance of following migration best practices during this process; nevertheless, such best practices are distributed across multiple documents. This article consolidates and builds upon existing electronic PROM implementation best practice recommendations to provide a comprehensive, up-to-date, single point of reference. It reflects the current consensus based on the significant advances in technology capabilities and knowledge gleaned from the growing evidence base on electronic migration and implementation, to balance the need for maintaining the integrity of the measure while optimizing respondent usability. It also specifies whether the practice is rooted in evidence or expert consensus, to enable those using these best practices to make informed and considered decisions when conducting migration.


Subject(s)
Patient Reported Outcome Measures , Humans , Consensus
16.
Psychiatr Serv ; 75(3): 275-282, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37933134

ABSTRACT

OBJECTIVE: Encouraging patients at risk for suicide to reduce access to potentially lethal medications and drugs is a key component of evidence-based suicide prevention. However, little research has been done to inform interventions for reducing intentional self-harm. METHODS: Semistructured interviews were conducted with 28 U.S. veterans who sought emergency care from the Veterans Health Administration between 2021 and 2023 to explore veterans' perspectives on medication-related interventions, including opinions on intervention components (e.g., medication return envelopes). Matrix analysis was used to aggregate data into categories, which were predefined by using constructs from the health belief model (e.g., perceived benefits). RESULTS: The participating veterans generally endorsed interventions as acceptable and were particularly supportive of distributing medication return envelopes. However, they often conceptualized these efforts as steps to prevent unintentional overdose or theft-not necessarily to prevent suicide-and rarely indicated that such interventions were appropriate for themselves. Across the interviews, participants identified important facilitators to care, such as ensuring that interventions were convenient and accounted for the perceived cost of disposing medications. Perspectives on engaging family or friends in interventions were mixed. The importance of the interventions was more readily acknowledged among participants with previous opioid use exposure-perspectives that appeared to stem from lived experiences. CONCLUSIONS: This study contributes important foundational knowledge that can be used to inform research and clinical initiatives aimed at preventing medication- and drug-related suicides.


Subject(s)
Drug Overdose , Emergency Medical Services , Suicide , Humans , Suicide Prevention , Drug Overdose/prevention & control , Friends
17.
Blood ; 143(2): 152-165, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-37832030

ABSTRACT

ABSTRACT: Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavorable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across 4 countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020. Survival risk factors were analyzed using both univariate and multivariate regression models. Overall survival (OS) was calculated using Kaplan-Meier statistics. First-line treatment regimens were stratified into standard- and higher-intensity regimens, and based on whether they incorporated a proteasome inhibitor (PI). A total of 281 patients (median age, 55 years) were included. Immunodeficiency of any kind was identified in 144 patients (51%), and 99 patients (35%) had HIV-positive results. The 5-year OS for the entire cohort was 36% (95% confidence interval, 30%-42%). In multivariate analysis, inferior OS was associated with Epstein-Barr virus-negative lymphoma, poor performance status, advanced stage, and bone marrow involvement. In an independent univariate analysis, the international prognostic index was associated with OS outcomes. Neither immunosuppression nor HIV infection, specifically, influenced OS. Among patients treated with curative intent (n = 234), the overall response rate was 72%. Neither the intensity of the treatment regimen nor the inclusion of PIs in first-line therapy was associated with OS. In this large retrospective study of patients with PBL, we identified novel risk factors for survival. PBL remains a challenging disease with poor long-term outcomes.


Subject(s)
Epstein-Barr Virus Infections , HIV Infections , Plasmablastic Lymphoma , Humans , Middle Aged , Plasmablastic Lymphoma/pathology , Retrospective Studies , HIV Infections/complications , HIV Infections/drug therapy , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , Prognosis
18.
Chemosphere ; 350: 141021, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38151062

ABSTRACT

The chemical properties of toxic cadmium and essential zinc are very similar, and organisms require intricate mechanisms that drive selective handling of metals. Previously regarded as unspecific "metal sponges", metallothioneins (MTLs) are emerging as metal selectivity filters. By utilizing C. elegans mtl-1 and mtl-2 knockout strains, metal accumulation in single worms, single copy fluorescent-tagged transgenes, isoform specific qPCR and lifespan studies it was possible to demonstrate that the handling of cadmium and zinc by the two C. elegans metallothioneins differs fundamentally: the MTL-2 protein can handle both zinc and cadmium, but when it becomes unavailable, either via a knockout or by elevated cadmium exposure, MTL-1 takes over zinc handling, leaving MTL-2 to sequester cadmium. This division of labour is reflected in the folding behaviour of the proteins: MTL-1 folded well in presence of zinc but not cadmium, the reverse was the case for MTL-2. These differences are in part mediated by a zinc-specific mononuclear His3Cys site in the C-terminal insertion of MTL-1; its removal affected the entire C-terminal domain and may shift its metal selectivity towards zinc. Overall, we uncover how metallothionein isoform-specific responses and protein properties allow C. elegans to differentiate between toxic cadmium and essential zinc.


Subject(s)
Cadmium , Caenorhabditis elegans , Animals , Caenorhabditis elegans/metabolism , Cadmium/toxicity , Metallothionein/metabolism , Zinc/metabolism , Metals/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism
19.
Cancer Epidemiol ; 88: 102513, 2024 02.
Article in English | MEDLINE | ID: mdl-38160571

ABSTRACT

BACKGROUND: Population-based information on cancer incidence and outcome are required to inform clinical practice and research; but contemporary data are lacking for many lymphoid cancer subtypes. METHODS: Set within a socio-demographically representative UK population of ∼4 million, data are from an established UK patient cohort (N = 22,414 diagnoses). Information on incidence (crude and age-standardised) and survival (overall and net) is presented for > 40 subtypes. RESULTS: The median diagnostic age was 69.9 years (interquartile range 59.1-78.3), but unlike many other cancers, lymphoid malignancies can be diagnosed at any age; different subtypes dominating at different ages. Males were more likely to be diagnosed than females (age-standardised sex rate ratio: 1.55 (95% Confidence Interval: 1.50,1.59)), and most subtypes had a male predominance, some more than three-fold (e.g. Burkitt lymphoma 3.26 (2.42, 4.40)). Five-year net survival estimates varied hugely, ranging from 97.4% (95% CI: 56.5, 99.9) in patients with hairy cell leukaemia to 31.6% (95% CI: 2.5, 69.8) in those with T-cell prolymphocytic leukaemia. No significant sex difference in survival were observed for the majority of diagnoses; one exception being classical Hodgkin lymphoma, where males had a higher mortality (Excess Mortality Ratio: 1.44 (95% CI: 1.11, 1.87)). An improvement in survival over time was observed for some, but not all, of the major diagnostic groups. CONCLUSIONS: Marked incidence and survival variations by subtype, sex and age confirm the heterogeneity of lymphoid neoplasms and highlight the importance of accurately characterising disease entities. Despite recent improvements, routine cancer registration of lymphoid neoplasms remains challenging and new issues continue to emerge; including the lack of an international consensus on classification and the recording of progressions and transformations. Furthermore, the increasing need for additional molecular and genomic information required for accurate classification is likely to impact negatively on the quality of cancer registration data, especially in low income countries.


Subject(s)
Hematologic Neoplasms , Hodgkin Disease , Lymphoma , Humans , Male , Female , Aged , Incidence , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/etiology , Lymphoma/epidemiology , United Kingdom/epidemiology
20.
Res Sq ; 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37961100

ABSTRACT

Health information technology (HIT) use among foreign-born adults of Middle Eastern and North African (MENA) descent living in America is an understudied population. They are currently categorized as "White" in the United States (US) on federal forms. The purpose was to uncover the prevalence of HIT use among MENA immigrants compared to US- and foreign-born White adults before and after adjusting for other factors. The 2011-2018 National Health Interview Survey data (n = 161,613; ages 18 + years) was analyzed. HIT uses evaluated were searching for health information, filling prescriptions, scheduling appointments, and communicating with healthcare providers via email (last 12 months). Crude and multivariable logistic regression models were used to estimate the odds of each HIT use, any HIT use, and all HIT uses before and after adjustment. The most common HIT use was looking up health information, with 46.4% of foreign-born adults of MENA, 47.8% of foreign-born White, and 51.2% of US-born White adults reporting its use (p = .0079). Foreign-born adults of MENA descent had lower odds (OR = 0.64; 95%CI = 0.56-0.74) of reporting any HIT use, but no difference in reporting all HIT uses compared to US-born White adults in adjusted models. This is the first study to explore HIT use among Americans of MENA descent. Patterns of HIT use among adults of MENA descent differ from White adults. Results contribute to growing body of literature showing the health of Americans of MENA descent differs from White Americans. A separate racial/ethnic identifier is needed to better capture HIT uses among populations of MENA descent.

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