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1.
Cureus ; 16(3): e56987, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38665744

ABSTRACT

Lumbar radiculopathy, characterized by pain radiating along a nerve root, significantly diminishes the quality of life due to its neuropathic nature. Patients' understanding of their illness and the coping strategies they employ directly influence how they manage their condition. Understanding these illness representations from the patient's perspective is crucial for healthcare providers seeking to optimize treatment outcomes. This study adopted a qualitative interpretive/constructive paradigm to explore this dynamic. A qualitative evidence synthesis approach, utilizing best-fit framework synthesis for data extraction, was applied to analyze primary qualitative studies focused on patient experiences with lumbar radiculopathy. Using SPiDER (Sample, Phenomenon of interest, Design, Evaluation, Research type) to guide the search strategy, extracted data was mapped against the Common-Sense Model of Self-Regulation (CSM) framework. Sixteen studies, with moderate to minor methodological quality concerns, were included in the analysis. Data mapping across CSM domains generated 14 key review findings. Results suggest that patients with high-threat illness representations often exhibit maladaptive coping behaviors (e.g., activity avoidance) driven by emotional responses. In contrast, problem-solving techniques appear to contribute to positive outcomes (e.g., exercise adherence and effective self-management) in patients who perceive their condition as less threatening. These findings highlight the potential benefits of interventions designed to reduce perceived threat levels and enhance self-efficacy in patients with lumbar radiculopathy, leading to improved self-management and ultimately better health outcomes.

2.
Proc Natl Acad Sci U S A ; 120(42): e2303115120, 2023 10 17.
Article in English | MEDLINE | ID: mdl-37824527

ABSTRACT

The Escherichia coli chemotaxis signaling pathway has served as a model system for the adaptive sensing of environmental signals by large protein complexes. The chemoreceptors control the kinase activity of CheA in response to the extracellular ligand concentration and adapt across a wide concentration range by undergoing methylation and demethylation. Methylation shifts the kinase response curve by orders of magnitude in ligand concentration while incurring a much smaller change in the ligand binding curve. Here, we show that the disproportionate shift in binding and kinase response is inconsistent with equilibrium allosteric models. To resolve this inconsistency, we present a nonequilibrium allosteric model that explicitly includes the dissipative reaction cycles driven by adenosine triphosphate (ATP) hydrolysis. The model successfully explains all existing joint measurements of ligand binding, receptor conformation, and kinase activity for both aspartate and serine receptors. Our results suggest that the receptor complex acts as an enzyme: Receptor methylation modulates the ON-state kinetics of the kinase (e.g., phosphorylation rate), while ligand binding controls the equilibrium balance between kinase ON/OFF states. Furthermore, sufficient energy dissipation is responsible for maintaining and enhancing the sensitivity range and amplitude of the kinase response. We demonstrate that the nonequilibrium allosteric model is broadly applicable to other sensor-kinase systems by successfully fitting previously unexplained data from the DosP bacterial oxygen-sensing system. Overall, this work provides a nonequilibrium physics perspective on cooperative sensing by large protein complexes and opens up research directions for understanding their microscopic mechanisms through simultaneous measurements and modeling of ligand binding and downstream responses.


Subject(s)
Chemotaxis , Escherichia coli Proteins , Chemotaxis/physiology , Methyl-Accepting Chemotaxis Proteins/metabolism , Escherichia coli Proteins/metabolism , Ligands , Histidine Kinase/metabolism , Escherichia coli/metabolism , Signal Transduction/physiology , Bacterial Proteins/metabolism
3.
J Pharm Bioallied Sci ; 15(Suppl 2): S934-S936, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37693993

ABSTRACT

Objective: To evaluate vertical marginal gap after cementation of Zr (zirconium) copings with palatal vent, open vent, and precementation technique on angulated abutments resulting from cement entrapment between intaglio surface of copings and angulated abutments. Materials and Methods: Twenty-four angled abutments and 24 CAD-CAM Zr copings were assigned to three groups depending on the type of cementation technique, comprising eight copings with palatal vent, open vent, and no vent, respectively. Vertical marginal gaps between abutment shoulder and coping margin were evaluated at four points: buccal, palatal, mesial, and distal. The readings were statistically analyzed. Results: The average mean value of vertical marginal gap at all sites for Group A with palatal vent was 158.45, for Group B with open vent was 151.84, and for Group C using precementation technique was 163.58. A statistically non-significant difference was seen for values between all sites (P > 0.05) for all groups. Conclusion: The average vertical marginal gap for Group B was comparatively lower compared to Groups A and C.

5.
Cureus ; 15(3): e36017, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37050998

ABSTRACT

Aim To study the role of vaginal hysterectomy in non-descent uterus and to compare it with abdominal hysterectomy with respect to operative time, intraoperative blood loss and complications, ambulation, and postoperative complications. Materials and methods A prospective non-randomized study was carried out on 200 cases at a rural tertiary care center in B.G. Nagara, Karnataka, India for a period of 18 months after obtaining institutional ethical committee approval. One hundred patients underwent a vaginal hysterectomy, and there other 100 underwent an abdominal hysterectomy for similar indications. Results Mean age, parity, mode of delivery, BMI, uterine size, and anesthesia were similar between the groups. The most common indication was fibroid uterus (50%). It was found that the vaginal hysterectomy group was associated with significantly reduced mean operative duration and a decline in postoperative Hemoglobin when compared to the abdominal hysterectomy group. Patients who underwent vaginal hysterectomy had less postoperative pain and were ambulated earlier and discharged earlier. Also, postoperative complications were more common in those who underwent abdominal hysterectomy. Conclusion Vaginal hysterectomy is a safe and the least invasive route and is associated with lesser complications and should be chosen as the preferred method of hysterectomy, whenever feasible.

6.
ArXiv ; 2023 Feb 23.
Article in English | MEDLINE | ID: mdl-36866223

ABSTRACT

The Escherichia coli chemotaxis signaling pathway has served as a model system for studying the adaptive sensing of environmental signals by large protein complexes. The chemoreceptors control the kinase activity of CheA in response to the extracellular ligand concentration and adapt across a wide concentration range by undergoing methylation and demethylation. Methylation shifts the kinase response curve by orders of magnitude in ligand concentration while incurring a much smaller change in the ligand binding curve. Here, we show that this asymmetric shift in binding and kinase response is inconsistent with equilibrium allosteric models regardless of parameter choices. To resolve this inconsistency, we present a nonequilibrium allosteric model that explicitly includes the dissipative reaction cycles driven by ATP hydrolysis. The model successfully explains all existing measurements for both aspartate and serine receptors. Our results suggest that while ligand binding controls the equilibrium balance between the ON and OFF states of the kinase, receptor methylation modulates the kinetic properties (e.g., the phosphorylation rate) of the ON state. Furthermore, sufficient energy dissipation is necessary for maintaining and enhancing the sensitivity range and amplitude of the kinase response. We demonstrate that the nonequilibrium allosteric model is broadly applicable to other sensor-kinase systems by successfully fitting previously unexplained data from the DosP bacterial oxygen-sensing system. Overall, this work provides a new perspective on cooperative sensing by large protein complexes and opens up new research directions for understanding their microscopic mechanisms through simultaneous measurements and modeling of ligand binding and downstream responses.

7.
J Breast Imaging ; 5(5): 538-545, 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-38416916

ABSTRACT

OBJECTIVE: To determine the prevalence of modifiable breast cancer risk factors among women engaged in screening mammography using nationally representative cross-sectional survey data and to inform potential opportunities for breast facilities to contribute to primary prevention. METHODS: 2018 National Health Interview Survey respondents who were women ages 40-74 years without history of breast cancer were included and then categorized based on whether they reported screening mammography within the prior two years. Proportions of these women reporting evidence-based modifiable breast cancer risk factors, including elevated body mass index (BMI), lack of physical activity, or moderate or heavy alcohol consumption were calculated and stratified by demographics. Multivariable logistic regression was used to estimate the association between these risk factors and sociodemographic characteristics. RESULTS: Among 4989 women meeting inclusion criteria and reporting screening mammography, 79% reported at least one modifiable risk factor. Elevated BMI was the most reported risk factor (67%), followed by lack of physical activity (24%) and alcohol consumption (16%). The majority of each race/ethnicity category reported at least one modifiable risk factor, with the highest proportion reported by Black respondents (90%). Asian, college educated, and higher-income participants were less likely to have at least one modifiable risk factor. CONCLUSION: Modifiable breast cancer risk factors are prevalent among women engaged in screening mammography. This provides potential opportunities for breast imaging facilities to contribute to the primary prevention of breast cancer by providing resources for lifestyle modification at the time of screening mammography.


Subject(s)
Breast Neoplasms , Mammography , Humans , Female , Mammography/adverse effects , Breast Neoplasms/diagnosis , Prevalence , Cross-Sectional Studies , Early Detection of Cancer/adverse effects , Risk Factors , Surveys and Questionnaires , Primary Prevention
8.
Front Behav Neurosci ; 16: 850623, 2022.
Article in English | MEDLINE | ID: mdl-35493954

ABSTRACT

Major depression is a significant medical issue impacting millions of individuals worldwide. Identifying factors contributing to its manifestation has been a subject of intense investigation for decades and several targets have emerged including sex hormones and the immune system. Indeed, an extensive body of literature has demonstrated that sex hormones play a critical role in modulating brain function and impacting mental health, especially among female organisms. Emerging findings also indicate an inflammatory etiology of major depression, revealing new opportunities to supplement, or even supersede, currently available pharmacological interventions in some patient populations. Given the established sex differences in immunity and the profound impact of fluctuations of sex hormone levels on the immune system within the female, interrogating how the endocrine, nervous, and immune systems converge to impact women's mental health is warranted. Here, we review the impacts of endogenous estrogens as well as exogenously administered estrogen-containing therapies on affect and immunity and discuss these observations in the context of distinct reproductive milestones across the female lifespan. A theoretical framework and important considerations for additional study in regards to mental health and major depression are provided.

9.
Proc (Bayl Univ Med Cent) ; 35(1): 93-95, 2022.
Article in English | MEDLINE | ID: mdl-34970049

ABSTRACT

An association has been reported between factor VIII and arterial thrombosis such as ischemic stroke and myocardial infarction. We report a 36-year-old man who had a myocardial infarction despite lacking traditional cardiac risk factors. He developed end-stage heart failure and renal insufficiency necessitating a HeartMate II left ventricular assist device (LVAD). While on the transplant list, he experienced two episodes of LVAD thrombosis 6 months apart, prompting device exchange and escalation of anticoagulation therapy. He eventually underwent a successful heart-kidney transplant before suffering an extensive left lower extremity deep vein thrombosis 6 weeks later. A thrombophilia workup revealed elevated factor VIII activity of 319% (normal range, 50%-150%). He was placed on indefinite anticoagulation with apixaban with no further thrombotic episode in 18 months of follow-up to date.

10.
Radiology ; 301(3): 712-720, 2021 12.
Article in English | MEDLINE | ID: mdl-34546133

ABSTRACT

Background To address disparities in lung cancer screening (LCS) that may exclude large numbers of high-risk African American smokers, revised U.S. Preventive Services Task Force (USPSTF) recommendations lowered LCS eligibility thresholds. However, there are limited recent data about the impact of newly revised guidelines on disparities in LCS eligibility. Purpose To evaluate the impact of revised USPSTF guidelines on racial and ethnic disparities in LCS eligibility. Materials and Methods Cross-sectional survey data from 20 states were retrospectively evaluated from the 2019 Behavioral Risk Factor Surveillance System survey (median response rate, 49.4%). Respondents without a history of lung cancer aged 55-79 years (ie, under the previous guidelines) or aged 50-79 years (ie, under the revised guidelines) were included. Multivariable logistic regression analyses were performed to evaluate the association between race and ethnicity and LCS eligibility. All analyses were performed accounting for complex survey design features (ie, weighting, stratification, and clustering). Results Under previous guidelines, 11% of 67 567 weighted survey respondents were eligible for LCS (White [12%], Hispanic [4%], African American [7%], American Indian [17%], Asian or Pacific Islander [4%], and other [12%]). Under revised USPSTF guidelines, 14% of 77 689 weighted survey respondents were eligible for LCS (White [15%], Hispanic [5%], African American [9%], American Indian [21%), Asian or Pacific Islander [5%], and other [18%]). Compared with White respondents, African American respondents (adjusted odds ratio [OR] = 0.36; 95% CI: 0.27, 0.47; P < .001) and Hispanic respondents (adjusted OR = 0.15; 95% CI: 0.09, 0.24; P < .001) were less likely to be eligible for LCS under previous guidelines. African American respondents (adjusted OR = 0.39; 95% CI: 0.32, 0.47; P < .001) and Hispanic respondents (adjusted OR = 0.15; 95% CI: 0.10, 0.23; P < .001) were less likely to be eligible under the revised guidelines. The Wald test showed no evidence of differences in the degree to which racial and ethnic minority groups were less likely to be eligible for LCS when comparing previous versus revised USPSTF guidelines (P = .76). Conclusion The revised U.S. Preventive Services Task Force guidelines (version 2.0) may perpetuate lung cancer disparities, as racial and ethnic minority groups are still less likely to be eligible for lung cancer screening. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Jacobs and Springfield in this issue.


Subject(s)
Ethnicity/statistics & numerical data , Healthcare Disparities/statistics & numerical data , Lung Neoplasms/diagnostic imaging , Racial Groups/statistics & numerical data , Tomography, X-Ray Computed/statistics & numerical data , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , United States
11.
PLoS Pathog ; 17(6): e1009632, 2021 06.
Article in English | MEDLINE | ID: mdl-34061907

ABSTRACT

Human immunodeficiency virus (HIV) vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) in the form of secretory IgA is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.


Subject(s)
Colon/virology , HIV Antibodies , HIV Infections , Immunoglobulin A, Secretory , Mucous Membrane/virology , Animals , Macaca mulatta , Mucous Membrane/immunology , Positron Emission Tomography Computed Tomography , Rectum
12.
Indian J Public Health ; 64(4): 339-344, 2020.
Article in English | MEDLINE | ID: mdl-33318382

ABSTRACT

BACKGROUND: Outpatient department (OPD) table surfaces frequently touched by patients and health-care workers in hospitals harbor potential pathogens and may act as source of infectious agents. OBJECTIVES: This study aimed to determine the pattern of bacterial contamination of surfaces of OPD tables in relation to existing cleaning/disinfection practices. METHODS: The descriptive study was conducted during July 2018-September 2018. A total of 128 swabs were collected from 32 OPD table surfaces immediately after cleaning or disinfection and then at 30 min, 2 h, and 4 h interval after cleaning or disinfection. Type and concentration of cleaner or disinfectant, number of cleaning strokes on table, and time of last washing of cleaning cloth with detergent were also noted from each location. Isolation, identification, and antibiotic susceptibility testing of the isolates were performed by standard microbiological techniques. RESULTS: A total of 337 bacterial isolates were recovered from 126 samples. Multidrug resistant Staphylococci, Acinetobacter, Pseudomonas, Klebsiella, and Escherichia coli were isolated. The mean bacterial colony count increased with time (P < 0.0001). Hand rub use, cleaning of OPD table surfaces with disinfectant, and more number of strokes with cleaning cloth resulted in decrease in colony count of bacteria isolated. CONCLUSION: High bacterial contamination of frequently touched OPD table surfaces with variety of potential pathogens like Staphylococcus, Acinetobacter, Pseudomonas, Klebsiella, and E. coli was detected. Hand hygiene among health-care workers and regular and frequent cleaning and disinfection of OPD table surfaces are highly recommended to prevent cross-transmission.


Subject(s)
Disinfection , Escherichia coli , Humans , India , Outpatients , Tertiary Care Centers
13.
EClinicalMedicine ; 27: 100551, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33150323

ABSTRACT

BACKGROUND: Male patients with breast cancer (BrC) have increased risk of developing 2nd-primary BrC (2nd-BrC). Given the relative rarity of male BrC, population-based registries are needed to analyze overall survival (OS) outcomes for these patients. METHODS: Using the Surveillance, Epidemiology and End Results registry of patients diagnosed from 1975 to 2016, a cohort study of men whose only malignancy was BrC (BrC-O; n = 6,475), and men who developed 2nd-BrC after initial BrC diagnosis (BrC-2; n = 85) was performed. The standardized incidence ratio (SIR) of 2nd-BrC, Kaplan-Meier OS and multivariable Cox regression modelling were performed. FINDINGS: The SIR for 2nd-BrC was 32.95 (95%CI:[23.85-44.38],p < 0.05). The majority (88%) of 2nd-BrC for BrC-2 were contralateral from 1st-BrC; suggesting the unlikeliness of miscoding local recurrences as 2nd-BrC for most patients. There was no statistically significant difference between rates of hormone (reported in 44%) or HER-2 (reported in 33%) receptor status between BrC-O and BrC-2, albeit with limited data. The 2nd-BrC for BrC-2 was significantly more likely to be localized or distant stage (rather than regional) than BrC-O. Median OS was 103 months (95% CI: [99, 108]) for BrC-O and 62 months (95% CI [49, 128] after 2nd-BrC. When sub-grouped by BrC stage, and when analyzed by Cox regression, there was no significant difference in OS between BrC-O and BrC-2. INTERPRETATION: Patients with male BrC are at significantly increased risk of 2nd BrC, but they can expect similar post-BrC prognosis (versus those without 2nd-BrC), after adjusting for patient demographics and tumor characteristics known to affect OS. FUNDING: None.

14.
Arthritis Care Res (Hoboken) ; 72(1): 18-26, 2020 01.
Article in English | MEDLINE | ID: mdl-30506552

ABSTRACT

OBJECTIVE: To identify longitudinal predictors of discordance between patients with rheumatoid arthritis (RA) and their health care providers, where patient global assessment of disease activity is substantially higher than provider global assessment. METHODS: This retrospective case-control study included 102 cases with positive discordance (i.e., ≥25 mm between patient and provider global assessments) and 102 controls without discordance who were matched for age, sex, RA duration, and Clinical Disease Activity Index (CDAI) score. Data were collected at the baseline visit (date of diagnosis or earliest available visit), the index visit (participation in a previous cross-sectional study), and at up to 11 additional visits before the index visit. Data included patient characteristics, disease activity measures, Disease Activity Score in 28 joints (3-variable) using the C-reactive protein level (DAS28-CRP), and medications. Data were analyzed by using linear and logistic regression models with smoothing splines for nonlinear trends. RESULTS: Overall, the mean age was 63 years, 75% of patients were female, and the mean RA duration was 10 years. Compared with controls, cases had higher rates of discordant visits during the 4 years before the index visit, and they had a higher CDAI score and DAS28-CRP earlier in the disease course. Cases more frequently had antinuclear antibodies, nonerosive disease, prior depression, or prior use of antidepressants or fibromyalgia medications. Disease-modifying medication use was not different between cases and controls. CONCLUSION: The findings inform new hypotheses about the relationships of disease activity and antinuclear antibodies to the later occurrence of positive discordance among patients with RA.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Health Status , Professional-Patient Relations , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index
15.
J Breast Imaging ; 2(2): 161-167, 2020 Mar 25.
Article in English | MEDLINE | ID: mdl-38424892

ABSTRACT

In the United States, at least 1.4 million adults identify as transgender. Despite growing national awareness, the transgender population experiences disparities in breast care access and breast health outcomes. One of the challenges of breast care delivery to transgender patients is the lack of evidence-based screening guidelines, which is likely partly due to the infrequency of transgender breast cancer cases. Several gender-affirming hormonal and surgical interventions are available that impact the imaging appearance of the breasts and the risk of breast cancer. Breast imaging radiologists should be familiar with the imaging appearance of expected findings and potential complications following gender-affirming interventions. It has been shown that the incidence of breast cancer in transgender women is higher than in natal males but still lower than in natal females, implying that estrogen supplementation confers an increased breast cancer risk. It is proposed that transgender women follow the screening guidelines for natal females if they have risk factors for breast cancer and received hormone therapy for > 5 years. However, further research is necessary, especially in transgender women who have no risk factors or received hormone therapy for ≤ 5 years. The breast cancer risk of presurgical transgender men is considered equivalent to that of natal females, but the risk markedly decreases following bilateral mastectomy. It is proposed that transgender men follow the screening guidelines for natal females if they have any preserved breast tissue, or that they undergo annual chest wall and axillary physical exam if they are status post bilateral mastectomy.

16.
Neurol India ; 67(Supplement): S118-S124, 2019.
Article in English | MEDLINE | ID: mdl-30688245

ABSTRACT

Magnetic resonance neurography (MRN) is recognized as the imaging modality of choice in the evaluation of patients with brachial plexopathy. It adds vital information to the results of the clinical evaluation and electrodiagnostic tests and facilitates patient management. Its indications include both trauma and non-traumatic forms of plexopathy such as inflammatory, neoplastic and compressive. This article will familiarize readers with the routine MRN protocol in clinical practice and discuss the utility of the different sequences. The timing of the scan is important, especially with reference to trauma and this has been discussed. Both the advantages and limitations of MRN have been elaborated upon.


Subject(s)
Brachial Plexus Neuropathies/diagnostic imaging , Brachial Plexus Neuropathies/pathology , Magnetic Resonance Imaging/methods , Brachial Plexus/anatomy & histology , Brachial Plexus/diagnostic imaging , Brachial Plexus/pathology , Humans , Male
17.
Int J Cardiovasc Imaging ; 35(1): 195-206, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30143921

ABSTRACT

The anteroposterior (AP) portable chest radiograph is routinely performed to evaluate cardiopulmonary status, however heart size can be misrepresented by inherent technical factors. Our aim was to determine diagnostic accuracy of cardiothoracic ratio (CTR) on AP chest radiographs relative to echocardiography, as well as relative to axial computed tomography (CT) and frontal CT scout images in predicting cardiac chamber enlargement. 200 subjects with both chest CT and AP chest radiograph within 1 month were retrospectively identified. Patients with pericardial effusion or obscured heart borders were excluded. 130 of these subjects had also undergone echocardiography. Transverse diameters of the heart and thorax were used to calculate CTRs on AP chest radiograph, scout CT, and axial CT images. A second reader was used to verify measurement accuracy and reproducibility. Statistical analysis of CTRs for AP chest radiograph, CT scout, and axial CT images were calculated using echocardiography as gold standard. AP chest radiographs had higher CTR values than axial and scout CT images (by 0.075, p < 0.001), larger measured heart diameters by approximately 3 cm (p < 0.001), and larger thoracic diameters by approximately 2 cm (p < 0.001). CTRs on AP chest radiographs calculated with a cutoff of 0.50 had sensitivity of 86% and specificity of 32%. Sensitivity and specificity were 61% and 66% respectively when using a cutoff of 0.55, and 34% and 92% respectively when using a cutoff of 0.60. A CTR of 60% is more appropriate than 50-55% when evaluating an AP chest radiograph for cardiac chamber enlargement due to its much higher specificity.


Subject(s)
Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Right Ventricular/diagnostic imaging , Radiography, Thoracic/methods , Ventricular Function, Left , Ventricular Function, Right , Ventricular Remodeling , Echocardiography, Transesophageal , Humans , Hypertrophy, Left Ventricular/physiopathology , Hypertrophy, Right Ventricular/physiopathology , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Tomography, X-Ray Computed
18.
Mol Biochem Parasitol ; 222: 70-80, 2018 06.
Article in English | MEDLINE | ID: mdl-29753659

ABSTRACT

Plasmodium falciparum DJ1 (PfDJ1) belongs to the DJ-1/ThiJ/PfpI superfamily whose members are present in all the kingdoms of life and exhibit diverse cellular functions and biochemical activities. The common feature of the superfamily is the class I glutamine amidotransferase domain with a conserved redox-active cysteine residue, which mediates various activities of the superfamily members, including anti-oxidative activity in PfDJ1 and human DJ1 (hDJ1). As the superfamily members represent diverse functional classes, to investigate if there is any sequence feature unique to hDJ1-like proteins, sequences of the representative proteins of different functional classes were compared and analysed. A novel motif unique to PfDJ1 and several other hDJ1-like proteins, with the consensus sequence of TSXGPX5FXLX5L, was identified that we designated as the hDJ1-subfamily motif (DJSM). Several mutations that have been associated with Parkinson's disease are also present in DJSM, suggesting its functional importance in hDJ1-like proteins. Mutations of the conserved residues of DJSM of PfDJ1 did not significantly affect overall secondary structure, but caused both a significant loss (S151A and P154A) and gain (L168A) of anti-oxidative activity. We also report that PfDJ1 has deglycase activity, which was significantly decreased in its mutants of the catalytic cysteine (C106A) and DJSM (S151A and P154A). Episomal expression of the catalytic cysteine (C106A) or DJSM (P154A) mutant decreased growth rates of parasites as compared to that of wild type parasites or parasites expressing wild type PfDJ1. S151 appears to properly position the nucleophilic elbow containing C106 and P154 forms a hydrogen bond with C106, which could be a reason for the loss of activities of PfDJ1 upon their mutations. Taken together, DJSM delineates PfDJ1 and other hDJ1-subfamily proteins from the remaining superfamily, and is critical for anti-oxidative and deglycase activities of PfDJ1.


Subject(s)
Oxidative Stress , Plasmodium falciparum/enzymology , Plasmodium falciparum/metabolism , Protein Deglycase DJ-1/chemistry , Protein Deglycase DJ-1/metabolism , Protozoan Proteins/chemistry , Protozoan Proteins/metabolism , Amino Acid Motifs , Amino Acid Sequence , Catalysis , Conserved Sequence , Humans , Plasmodium falciparum/chemistry , Plasmodium falciparum/genetics , Protein Deglycase DJ-1/genetics , Protozoan Proteins/genetics , Sequence Alignment
19.
Arthritis Res Ther ; 19(1): 212, 2017 09 26.
Article in English | MEDLINE | ID: mdl-28950896

ABSTRACT

BACKGROUND: Discordance between patients with rheumatoid arthritis (RA) and their rheumatology health care providers is a common and important problem. The objective of this study was to perform a comprehensive clinical evaluation of patient-provider discordance in RA. METHODS: A cross-sectional observational study was conducted of consecutive RA patients in a regional practice with an absolute difference of ≥ 25 points between patient and provider global assessments (possible points, 0-100). Data were collected for disease activity measures, clinical characteristics, comorbidities, and medications. In a prospective substudy, participants completed patient-reported outcome measures and underwent ultrasonographic assessment of synovial inflammation. Differences between the discordant and concordant groups were tested using χ2 and rank sum tests. Multivariable logistic regression was used to develop a clinical model of discordance. RESULTS: Patient-provider discordance affected 114 (32.5%) of 350 consecutive patients. Of the total population, 103 patients (29.5%) rated disease activity higher than their providers (i.e., 'positive' discordance); only 11 (3.1%) rated disease activity lower than their providers and were excluded from further analysis. Positive discordance correlated with negative rheumatoid factor and anticyclic citrullinated peptide antibodies, lack of joint erosions, presence of comorbid fibromyalgia or depression, and use of opioids, antidepressants, or anxiolytics, or fibromyalgia medications. In the prospective study, the group with positive discordance was distinguished by higher pain intensity, neuropathic type pain, chronic widespread pain and associated polysymptomatic distress, and limited functional health status. Depression was found to be an important mediator of positive discordance in low disease activity whereas the widespread pain index was an important mediator of positive discordance in moderate-to-high disease activity states. Ultrasonography scores did not reveal significant differences in synovial inflammation between discordant and concordant groups. CONCLUSIONS: The findings provide a deeper understanding of patient-provider discordance than previously known. New insights from this study include the evidence that positive discordance is not associated with unrecognized joint inflammation by ultrasonography and that depression and fibromyalgia appear to play distinct roles in determining positive discordance. Further work is necessary to develop a comprehensive framework for patient-centered evaluation and management of RA and associated comorbidities in patients in the scenario of patient-provider discordance.


Subject(s)
Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/pathology , Patient Reported Outcome Measures , Physicians , Adult , Cross-Sectional Studies , Female , Health Status , Humans , Male , Middle Aged , Prospective Studies , Severity of Illness Index
20.
Rheumatol Ther ; 4(1): 201-208, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28488206

ABSTRACT

INTRODUCTION: The patient global assessment of disease activity is a crucial component of various measures of disease activity in rheumatoid arthritis (RA). Our objective was to identify underlying latent traits driving the patient global assessment using a quantitative, multivariable data reduction approach. METHODS: This was a prospective cross-sectional study of consecutive patients with RA. The patient sample was stratified to include 50 patients with patient-provider discordance (i.e., at least 25-mm absolute difference between the patient and provider global assessments) and 20 patients with patient-provider concordance (i.e., less than 25-mm absolute difference between the patient and provider global assessments). Data were collected from the most recent rheumatology visit, including patient characteristics, current RA medications, and comorbidities. Participants completed several validated patient-reported outcome measures. The data were evaluated using factor analysis, and then linear regression was used to determine the variability in the patient global assessment explained by the factor scores. RESULTS: The study included 70 patients with mean age of 61 years, 73% female, and with mean disease duration of 8 years. The means (SD) for the patient and provider global assessments were 44.6 (22.7) and 20.1 (17.7), respectively. Factor analysis yielded eight factors that represented measurements of pain, fatigue, depression or anxiety symptoms, prior diagnosis of depression or anxiety, advanced age and degenerative arthritis, inability to participate, fibromyalgia (clinical diagnosis and Widespread Pain Index), and undetermined. Linear regression analysis showed that fibromyalgia explained the greatest proportion of the variance in the patient global assessment followed by the other factors. CONCLUSION: Latent factors underlying the patient global assessment include pain, depression and anxiety, inability to participate, fibromyalgia, advanced age, and degenerative arthritis.

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