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2.
J Clin Invest ; 134(11)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38652559

ABSTRACT

BACKGROUNDFeatures of consumptive coagulopathy and thromboinflammation are prominent in cerebral malaria (CM). We hypothesized that thrombogenic autoantibodies contribute to a procoagulant state in CM.METHODSPlasma from children with uncomplicated malaria (UM) (n = 124) and CM (n = 136) was analyzed by ELISA for a panel of 8 autoantibodies including anti-platelet factor 4/polyanion (anti-PF4/P), anti-phospholipid, anti-phosphatidylserine, anti-myeloperoxidase, anti-proteinase 3, anti-dsDNA, anti-ß-2-glycoprotein I, and anti-cardiolipin. Plasma samples from individuals with nonmalarial coma (NMC) (n = 49) and healthy controls (HCs) (n = 56) were assayed for comparison. Associations with clinical and immune biomarkers were determined using univariate and logistic regression analyses.RESULTSMedian anti-PF4/P and anti-PS IgG levels were elevated in individuals with malaria infection relative to levels in HCs (P < 0.001) and patients with NMC (PF4/P: P < 0.001). Anti-PF4/P IgG levels were elevated in children with CM (median = 0.27, IQR: 0.19-0.41) compared with those with UM (median = 0.19, IQR: 0.14-0.22, P < 0.0001). Anti-PS IgG levels did not differ between patients with UM and those with CM (P = 0.39). When patients with CM were stratified by malaria retinopathy (Ret) status, the levels of anti-PF4/P IgG correlated negatively with the peripheral platelet count in patients with Ret+ CM (Spearman's rho [Rs] = 0.201, P = 0.04) and associated positively with mortality (OR = 15.2, 95% CI: 1.02-275, P = 0.048). Plasma from patients with CM induced greater platelet activation in an ex vivo assay relative to plasma from patients with UM (P = 0.02), and the observed platelet activation was associated with anti-PF4/P IgG levels (Rs= 0.293, P = 0.035).CONCLUSIONSThrombosis mediated by elevated anti-PF4/P autoantibodies may be one mechanism contributing to the clinical complications of CM.


Subject(s)
Autoantibodies , Malaria, Cerebral , Platelet Factor 4 , Humans , Malaria, Cerebral/immunology , Malaria, Cerebral/blood , Autoantibodies/blood , Autoantibodies/immunology , Female , Male , Platelet Factor 4/immunology , Platelet Factor 4/blood , Child , Child, Preschool , Infant , Polyelectrolytes , Thrombosis/immunology , Thrombosis/blood
3.
Am J Clin Pathol ; 161(2): 122-129, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37936260

ABSTRACT

OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is a rare but life-threatening condition that requires rapid diagnosis for proper management. Laboratory testing should only be performed on patients with intermediate- or high-risk pretest probability. The platelet factor 4 (PF4) enzyme-linked immunosorbent assay (ELISA) is the screening test that should be confirmed by higher specificity testing such as the heparin-induced platelet aggregation (HIPA) or the serotonin release assay (SRA). This study aims to evaluate the performance of the HIPA in comparison to the SRA, establish cutoffs of the PF4 ELISA to predict positivity for HIPA/SRA, and study the mortality rate between patients with suspected HIT confirmed as HIT positive vs negative. METHODS: All positive PF4 ELISA cases with confirmatory HIPA and SRA testing were included. As the SRA was considered the gold standard, the HIPA performance was evaluated in comparison to SRA before and after the implementation of a new standardized interpretation guide in 2022. The mortality of these cases was also documented by chart reviews. RESULTS: In total, 232 cases with positive or indeterminate anti-PF4 IgG ELISA had confirmatory testing with HIPA and SRA. The sensitivity of the HIPA improved from 55.4% in 2018 to 2021 to 73.8% in 2022. The specificity remained similarly high in 2018 to 2021 vs 2022 (94.9% vs 87.5%). The negative predictive value (NPV) improved in 2022. The PF4 optical density cutoff to predict the positivity of SRA was 0.85 vs 1.47 to predict the positivity of HIPA but decreased to 0.83 when combining HIPA and/or SRA. There was no significant difference in mortality between patients with suspected HIT confirmed positive vs negative. CONCLUSIONS: Although the HIPA has a lower sensitivity than the SRA, the new standardized interpretation guide improved its sensitivity and NPV in 2022. Future improvements are needed to use the HIPA as a stand-alone confirmatory test with the goal to shorten hospital length of stay and expedite proper anticoagulation management.


Subject(s)
Heparin , Thrombocytopenia , Humans , Heparin/adverse effects , Platelet Aggregation , Serotonin , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Enzyme-Linked Immunosorbent Assay , Anticoagulants/adverse effects
4.
Int J Sports Phys Ther ; 18(6): 1299-1307, 2023.
Article in English | MEDLINE | ID: mdl-38050553

ABSTRACT

Background: The Basas Spanish Squat with electrical stimulation (E-stim) has shown promising results as a potential key exercise in treatment of athletes with patellar tendinopathy. Gold standard exercise therapy for tendon injuries consists of tendon loading exercises, or exercises that appropriately applies high levels of mechanical strain to the tendon. The theoretical pathway in which the Basas Spanish Squat with E-stim improves tendinopathy has been speculated to be the additional strain applied through the patellar tendon during superimposition of E-stim. This theory, however, has yet to be confirmed. Purpose: The purpose of this case series was to compare patellar tendon strain, during the Basas Spanish Squat with, and without E-stim, and open kinetic chain knee extension. Methods: Four healthy participants performed the three exercises while a physical therapist collected simultaneous unilateral ultrasound images from the patellar tendon. Strain was calculated as the change in patellar tendon length during contraction divided by the resting length. Results: Amongst all participants, patellar tendon strain was smallest during the Basas Spanish Squat without E-stim, followed by the open kinetic chain knee extension at 60% maximum voluntary isometric contraction. The Basas Spanish Squat with E-stim yielded approximately double or more strain compared to the without E-stim condition and demonstrated higher level of strain compared to open kinetic chain knee extension in all participants. Conclusion: The findings reflect a clear trend of increased strain through the patellar tendon when E-stim was superimposed. The results support the theory that the Basas Spanish Squat with E-stim increases patellar tendon strain and could explain the reported clinical benefits in individuals with patellar tendinopathy. Level of Evidence: 4, Case series.

5.
Blood Adv ; 7(16): 4631-4632, 2023 08 22.
Article in English | MEDLINE | ID: mdl-37578809
6.
Life (Basel) ; 13(3)2023 Feb 23.
Article in English | MEDLINE | ID: mdl-36983779

ABSTRACT

Neutrophil Extracellular Traps (NETs) are large neutrophil-derived structures composed of decondensed chromatin, cytosolic, and granule proteins. NETs play an important role in fighting infection, inflammation, thrombosis, and tumor progression processes, yet their fast and reliable identification has been challenging. Smudge cells (SCs) are a subcategory of white cells identified by CellaVision®, a hematology autoanalyzer routinely used in clinical practice that uses digital imaging to generate "manual" differentials of peripheral blood smears. We hypothesize that a proportion of cells identified in the SC category by CellaVision® Hematology Autoanalyzers are actually NETs. We demonstrate that NET-like SCs are not present in normal blood samples, nor are they an artifact of smear preparation. NET-like SCs stain positive for neutrophil markers such as myeloperoxidase, leukocyte alkaline phosphatase, and neutrophil elastase. On flow cytometry, cells from samples with high percent NET-like SCs that are positive for surface DNA are also positive for CD45, myeloperoxidase and markers of neutrophil activation and CD66b. Samples with NET-like SCs have a strong side fluorescent (SFL) signal on the white count and nucleated red cells (WNR) scattergram, representing cells with high nucleic acid content. When compared to patients with low percent SCs, those with a high percentage of SCs have a significantly higher incidence of documented bacterial and viral infections. The current methodology of NET identification is time-consuming, complicated, and cumbersome. In this study, we present data supporting identification of NETs by CellaVision®, allowing for easy, fast, cost-effective, and high throughput identification of NETs that is available in real time and may serve as a positive marker for a bacterial or viral infections.

7.
J Thromb Haemost ; 21(4): 728-743, 2023 04.
Article in English | MEDLINE | ID: mdl-36696218

ABSTRACT

Artificial Intelligence and machine-learning (ML) studies are increasingly populating the life science space and some have also started to integrate certain clinical decision support tasks. However, most of the activities within this space understandably remain within the investigational domain and are not yet ready for broad use in healthcare. In short, artificial intelligence/ML is still in an infancy stage within the healthcare arena, and we are nowhere near reaching its full potential. Various factors have contributed to this slow adoption rate within healthcare, which include but are not limited to data accessibility and integrity issues, paucity of specialized data science personnel, certain regulatory measures, and various voids within the ML operational platform domain. However, these obstacles and voids have also introduced us to certain opportunities to better understand this arena as we fully embark on this new journey, which undoubtedly will become a major part of our future patient care activities. Considering the aforementioned needs, this review will be concentrating on various ML studies within the coagulation and hemostasis space to better understand their shared study needs, findings, and limitations. However, the ML needs within this subspecialty of medicine are not unique and most of these needs, voids, and limitations also apply to the other medical disciplines. Therefore, this review will not only concentrate on introducing the audience to ML concepts and ML study design elements but also on where the future within this arena in medicine is leading us.


Subject(s)
Artificial Intelligence , Decision Support Systems, Clinical , Humans , Machine Learning , Blood Coagulation , Forecasting
8.
ASAIO J ; 68(12): 1428-1433, 2022 12 01.
Article in English | MEDLINE | ID: mdl-35671537

ABSTRACT

Anticoagulation during extracorporeal membrane oxygenation (ECMO) for Coronovirus Disease 2019 (COVID-19) can be performed by direct or indirect thrombin inhibitors but differences in outcomes with these agents are uncertain. A retrospective, multicenter study was conducted. All consecutive adult patients with COVID-19 placed on ECMO between March 1, 2020 and April 30, 2021 in participating centers, were included. Patients were divided in groups receiving either a direct thrombin inhibitor (DTI) or an indirect thrombin inhibitor such as unfractionated heparin (UFH). Overall, 455 patients with COVID-19 from 17 centers were placed on ECMO during the study period. Forty-four patients did not receive anticoagulation. Of the remaining 411 patients, DTI was used in 160 (39%) whereas 251 (61%) received UFH. At 90-days, in-hospital mortality was 50% (DTI) and 61% (UFH), adjusted hazard ratio: 0.81, 95% confidence interval (CI): 0.49-1.32. Deep vein thrombosis [adjusted odds ratio (aOR): 2.60, 95% CI: 0.90-6.65], ischemic (aOR: 1.58, 95% CI: 0.18-14.0), and hemorrhagic (aOR:1.22, 95% CI: 0.39-3.87) stroke were similar with DTI in comparison to UFH. Bleeding requiring transfusion was lower in patients receiving DTI (aOR: 0.40, 95% CI: 0.18-0.87). Anticoagulants that directly inhibit thrombin are associated with similar in-hospital mortality, stroke, and venous thrombosis and do not confer a higher risk of clinical bleeding in comparison to conventional heparin during ECMO for COVID-19.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Stroke , Adult , Humans , Heparin/therapeutic use , Extracorporeal Membrane Oxygenation/adverse effects , Thrombin , Retrospective Studies , COVID-19/therapy , Anticoagulants/therapeutic use , Hemorrhage/etiology
9.
Res Pract Thromb Haemost ; 6(4): e12667, 2022 May.
Article in English | MEDLINE | ID: mdl-35734100

ABSTRACT

Background: The serotonin release assay (SRA) is considered the gold standard for diagnosis of heparin-induced thrombocytopenia (HIT). Although the SRA holds high sensitivity and specificity when results are definitive, up to 10% of samples from patients with suspected HIT yield "indeterminate" results. Objectives: We aimed to study the clinical course of patients with indeterminate results. Methods: We conducted a cohort analysis of 2056 patients that underwent SRA testing. Results: Of 2056 total patients, 152 (7.4%) had indeterminate assays. The prevalence of thrombocytopenia <50,000 × 106 was higher in patients with an indeterminate or positive SRA, compared with a negative SRA (39.5% and 40.0% vs. 27.5%, p < 4.0 × 10-4). Patients with an indeterminate SRA were more likely to have been treated in the intensive care unit than patients with a positive SRA (93.3% vs. 73.7%, p = 0.03). The mean thrombocytopenia, timing of platelet count fall, thrombosis or other sequelae, and other causes for thrombocytopenia score in patients with indeterminate SRA was 2.9, corresponding to a HIT probability of <5%. Of 152 patients, 128 (78.9%) had heparin-PF4 optical densities (ODs) below 0.60 OD, whereas four patients (2.6%) had ODs above 2.00 OD. Inpatient mortality was significant in patients with indeterminate SRAs compared with positive or negative SRA (49.3% vs. 21.1% and 27.2%, p < 2.4 × 10-10). Conclusions: Our data suggest that an indeterminate SRA may signal an in vivo platelet activation process that is not related to heparin but is associated with increased mortality.

10.
Ann Hematol ; 101(3): 541-548, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35039901

ABSTRACT

The presence of leg ulcers in individuals with sickle cell disease often represents an early sign of vasculopathy and future end organ damage. Pathophysiological mechanisms of formation and evolution of leg ulcers are poorly understood; nevertheless, HbF has been associated with lower incidence of leg ulcers, while hydroxyurea has been correlated with high risk of leg ulcers. As a result, there is hesitation regarding hydroxyurea use in patients with SCD and leg ulcers. In this study, we aim to define (1) a target of HbF that offers protection against leg ulcer development and (2) the impact of hydroxyurea therapy on leg ulcer prevalence. Our study demonstrated that in order to reduce leg ulcer incidence by one-third, a HbF > 25% is needed, a threshold not commonly reached and maintained in the adult SCD population. Importantly, leg ulcer incidence appears to be independent of HU use (p = 0.50). Our interpretation of this data is that the use of HU in a patient with SCD and leg ulcers should be guided by a careful assessment of risks and benefits of this therapeutic modality.


Subject(s)
Anemia, Sickle Cell/drug therapy , Antisickling Agents/therapeutic use , Fetal Hemoglobin/analysis , Hydroxyurea/therapeutic use , Leg Ulcer/etiology , Adult , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/complications , Antisickling Agents/adverse effects , Female , Humans , Hydroxyurea/adverse effects , Incidence , Leg Ulcer/blood , Male , Middle Aged , Risk Factors , Young Adult
11.
J Clin Rheumatol ; 28(2): e440-e443, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34348368

ABSTRACT

BACKGROUND/OBJECTIVE: Demand for rheumatology care has steadily increased in recent years. The number of specialists in this field, however, seems insufficient. No recent studies have diagnosed the attributes of rheumatology training in Latin America. METHODS: This is a descriptive cross-sectional study. We obtained data on each country through local rheumatologists of the Pan-American League Against Rheumatism, who acted as principal investigators for participating countries. Our sample was analyzed and described through means and standard deviations or through frequencies and percentages, depending on the variable. RESULTS: Countries with the most rheumatology-training programs were Brazil (n = 50), Argentina (n = 18), and Mexico (n = 15). Ecuador, Honduras, and Nicaragua do not have rheumatology-training programs. The countries with the most available slots for rheumatology residents were Brazil (n = 126) and Argentina (n = 36). To be admitted into rheumatology training, candidates were required to have completed graduate studies in internal medicine in 42.1% of the programs. In 8 countries (42.1%), residents are not required to pay tuition; the median cost of tuition in the remaining countries is US $528 (interquartile range, US $2153). CONCLUSIONS: Conditions associated with rheumatology training in Latin America vary. Significant differences exist in income and tuition fees for residents, for example, and 4 countries in Latin America do not currently offer programs. Information collected in this study will be useful when comparing the status of rheumatology services offered in Latin America with those in other countries. Most countries require a wider offering of rheumatology-training programs, as well as more available slots.


Subject(s)
Rheumatic Diseases , Rheumatology , Cross-Sectional Studies , Humans , Latin America/epidemiology , Rheumatic Diseases/epidemiology , Rheumatic Diseases/therapy , Rheumatologists
12.
Rheumatol Int ; 42(1): 41-49, 2022 01.
Article in English | MEDLINE | ID: mdl-34739574

ABSTRACT

The objective of our study was to describe knowledge, attitudes and practices of Latin-American rheumatology patients regarding management and follow-up of their disease during COVID-19 pandemic. A cross-sectional observational study was conducted using a digital anonymous survey. Rheumatic patients ≥ 18 years from non-English-speaking PANLAR countries were included. Our survey included 3502 rheumatic patients living in more than 19 Latin-American countries. Median age of patients was 45.8(36-55) years and the majority (88.9%) was female. Most frequently self-reported disease was rheumatoid arthritis (48.4%). At least one anti-rheumatic treatment was suspended by 23.4% of patients. Fear of contracting SARS-Cov2 (27.7%) and economic issues (25%) were the most common reasons for drug discontinuation. Self-rated disease activity increased from 30 (7-50) to 45 (10-70) points during the pandemic. Communication with their rheumatologist during the pandemic was required by 55.6% of patients, mainly by telephone calls (50.2%) and social network messages (47.8%). An adequate knowledge about COVID-19 was observed in 43% of patients. Patients with rheumatic diseases in Latin America were negatively affected by the COVID-19 pandemic. An increase in self-rated disease activity, a reduction in medication adherence, and hurdles for medical follow-up were reported. Teleconsultation was perceived as a valid alternative to in-person visits during the pandemic.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19 , Health Knowledge, Attitudes, Practice , Rheumatic Diseases/drug therapy , Cross-Sectional Studies , Humans , Latin America , Pandemics
13.
mBio ; 12(6): e0297221, 2021 12 21.
Article in English | MEDLINE | ID: mdl-34809453

ABSTRACT

Lipids play a fundamental role in fungal cell biology, being essential cell membrane components and major targets of antifungal drugs. A deeper knowledge of lipid metabolism is key for developing new drugs and a better understanding of fungal pathogenesis. Here, we built a comprehensive map of the Histoplasma capsulatum lipid metabolic pathway by incorporating proteomic and lipidomic analyses. We performed genetic complementation and overexpression of H. capsulatum genes in Saccharomyces cerevisiae to validate reactions identified in the map and to determine enzymes responsible for catalyzing orphan reactions. The map led to the identification of both the fatty acid desaturation and the sphingolipid biosynthesis pathways as targets for drug development. We found that the sphingolipid biosynthesis inhibitor myriocin, the fatty acid desaturase inhibitor thiocarlide, and the fatty acid analog 10-thiastearic acid inhibit H. capsulatum growth in nanomolar to low-micromolar concentrations. These compounds also reduced the intracellular infection in an alveolar macrophage cell line. Overall, this lipid metabolic map revealed pathways that can be targeted for drug development. IMPORTANCE It is estimated that 150 people die per hour due to the insufficient therapeutic treatments to combat fungal infections. A major hurdle to developing antifungal therapies is the scarce knowledge on the fungal metabolic pathways and mechanisms of virulence. In this context, fungal lipid metabolism is an excellent candidate for developing drugs due to its essential roles in cellular scaffolds, energy storage, and signaling transductors. Here, we provide a detailed map of Histoplasma capsulatum lipid metabolism. The map revealed points of this fungus lipid metabolism that can be targeted for developing antifungal drugs.


Subject(s)
Histoplasma/genetics , Histoplasma/metabolism , Lipid Metabolism , Fatty Acids/biosynthesis , Fungal Proteins/genetics , Fungal Proteins/metabolism , Histoplasma/growth & development , Histoplasmosis/microbiology , Humans , Lipidomics , Proteomics , Sphingolipids/biosynthesis
14.
Article in English | MEDLINE | ID: mdl-34360252

ABSTRACT

The current study was conducted to compare muscle damage biomarkers in single- vs. multi-match weeks in elite soccer players for two consecutive seasons. A secondary objective was to analyze the influence of playing position and exposure time on muscle damage in single- vs. multi-match weeks. This is a prospective cohort study performed in a professional elite soccer club in the English Premier League during the 2018-2019 and 2019-2020 seasons up until the lockdown due to the COVID-19 pandemic. Data were collected in the Medical Department Room of an English Premier League Club before and after the soccer game from a total of 29 elite soccer players (mean ± S.D.; age = 27.59 ± 3.83 years; height = 1.83 ± 0.05 m; body mass = 80.16 ± 7.45 kg) who were enrolled in the club during both seasons. The main outcome measurements were creatine kinase (CK), weight, lean mass, % fat DEXA, high speed running, total distance, density of total distance and high-speed running and wellbeing questionnaires. Significance was set at p < 0.05. Players who completed more than 60 min in the previous game had significantly increased pregame CK levels and fatigue in multi-match weeks. Midfielders had both significantly increased pregame CK and muscle soreness in multi-match weeks. Midfielders and players with an exposure time of at least 60 min showed higher pregame CK values that should play a key role for deciding substitutions.


Subject(s)
Athletic Performance , COVID-19 , Soccer , Adult , Biomarkers , Communicable Disease Control , Humans , Muscles , Pandemics , Prospective Studies , SARS-CoV-2 , Seasons , Young Adult
15.
J Rheumatol ; 48(10): 1616-1622, 2021 10.
Article in English | MEDLINE | ID: mdl-34329183

ABSTRACT

OBJECTIVE: To describe the effect of the coronavirus disease 2019 (COVID-19) pandemic on Latin American rheumatologists from a professional, economic, and occupational point of view. METHODS: We conducted an observational cross-sectional study using an online survey sent to rheumatologists of each non-English-speaking country member of the Pan American League of Rheumatology Associations (PANLAR). A specific questionnaire was developed. RESULTS: Our survey included 1097 rheumatologists from 19 Latin American countries. Median (IQR) age of respondents was 48 (40-59) years and 618 (56.3%) were female. Duration of practice since graduation as a rheumatologist was 17 years, and 585 (53.3%) were aged < 50 years. Most rheumatologists worked in private practice (81.8%) and almost half worked in institutional outpatient centers (55%) and inpatient care (49.9%). The median number of weekly hours (IQR) of face-to-face practice before the pandemic was 27 (15-40) hours, but was reduced to 10 (5-20) hours during the pandemic. Telehealth was used by 866 (78.9%) respondents during the pandemic. Most common methods of communication were video calls (555; 50.6%), telephone calls (499; 45.5%), and WhatsApp voice calls (423; 38.6%). A reduction in monthly wages was reported by 946 (86.2%) respondents. Consultation fees also were reduced and 88 (8%) rheumatologists stated they had lost their jobs. A reduction in patient adherence to medication was reported by nearly 50% of respondents. Eighty-one (7.4%) rheumatologists received a COVID-19 diagnosis and 7 (8.6%) of them were hospitalized. CONCLUSION: The COVID-19 pandemic has reshaped rheumatology practice in Latin America and has had a profound effect on rheumatologists' behaviors and clinical practice.


Subject(s)
COVID-19 , Rheumatology , COVID-19 Testing , Cross-Sectional Studies , Female , Humans , Latin America/epidemiology , Middle Aged , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
16.
Front Cell Dev Biol ; 9: 665886, 2021.
Article in English | MEDLINE | ID: mdl-34249919

ABSTRACT

Dental pulp stem cells (DPSCs) are a source of postnatal stem cells essential for maintenance and regeneration of dentin and pulp tissues. Previous in vivo transplantation studies have shown that DPSCs are able to give rise to odontoblast-like cells, form dentin/pulp-like structures, and induce blood vessel formation. Importantly, dentin formation is closely associated to blood vessels. We have previously demonstrated that DPSC-induced angiogenesis is VEGFR-2-dependent. VEGFR-2 may play an important role in odontoblast differentiation of DPSCs, tooth formation and regeneration. Nevertheless, the role of VEGFR-2 signaling in odontoblast differentiation of DPSCs is still not well understood. Thus, in this study we aimed to determine the role of VEGFR-2 in odontoblast differentiation of DPSCs by knocking down the expression of VEGFR-2 in DPSCs and studying their odontoblast differentiation capacity in vitro and in vivo. Isolation and characterization of murine DPSCs was performed as previously described. DPSCs were induced by VEGFR-2 shRNA viral vectors transfection (MOI = 10:1) to silence the expression of VEGFR-2. The GFP+ expression in CopGFP DPSCs was used as a surrogate to measure the efficiency of transfection and verification that the viral vector does not affect the expression of VEGFR-2. The efficiency of viral transfection was shown by significant reduction in the levels of VEGFR-2 based on the Q-RT-PCR and immunofluorescence in VEGFR-2 knockdown DPSCs, compared to normal DPSCs. VEGFR-2 shRNA DPSCs expressed not only very low level of VEGFR-2, but also that of its ligand, VEGF-A, compared to CopGFP DPSCs in both transcriptional and translational levels. In vitro differentiation of DPSCs in osteo-odontogenic media supplemented with BMP-2 (100 ng/ml) for 21 days demonstrated that CopGFP DPSCs, but not VEGFR-2 shRNA DPSCs, were positive for alkaline phosphatase (ALP) staining and formed mineralized nodules demonstrated by positive Alizarin Red S staining. The expression levels of dentin matrix proteins, dentin matrix protein-1 (Dmp1), dentin sialoprotein (Dspp), and bone sialoprotein (Bsp), were also up-regulated in differentiated CopGFP DPSCs, compared to those in VEGFR-2 shRNA DPSCs, suggesting an impairment of odontoblast differentiation in VEGFR-2 shRNA DPSCs. In vivo subcutaneous transplantation of DPSCs with hydroxyapatite (HAp/TCP) for 5 weeks demonstrated that CopGFP DPSCs were able to differentiate into elongated and polarized odontoblast-like cells forming loose connective tissue resembling pulp-like structures with abundant blood vessels, as demonstrated by H&E, Alizarin Red S, and dentin matrix staining. On the other hand, in VEGFR-2 shRNA DPSC transplants, odontoblast-like cells were not observed. Collagen fibers were seen in replacement of dentin/pulp-like structures. These results indicate that VEGFR-2 may play an important role in dentin regeneration and highlight the potential of VEGFR-2 modulation to enhance dentin regeneration and tissue engineering as a promising clinical application.

17.
Hemoglobin ; 45(2): 136-139, 2021 Mar.
Article in English | MEDLINE | ID: mdl-34134586

ABSTRACT

Sickle cell disease variants include hemoglobinopathies that result from inheritance of the sickle cell globin mutation with another globin mutation. The most common variants include the homozygous disease state (Hb SS disease), Hb S (HBB: c.20A>T)/Hb C (HBB: c.19G>A) disease and Hb S/ß-thalassemia (Hb S/ß-thal). Other rare/less common variants such as Hb S/Hb E (HBB: c.79G>A) and Hb S/HPFH [hereditary persistence of fetal hemoglobin (Hb)] disease exist. We report the first case of compound heterozygosity for Hb S and Hb Haringey (HBB: c.131A>G) in a 35-year-old male following a positive sickle screen test on hospital admission for pancreatitis. Ion exchange high performance liquid chromatography (HPLC), Hb electrophoresis and genetic sequencing were utilized to identify a new sickle Hb variant: Hb S/Hb Haringey. Hb S/Hb Haringey is a newly discovered sickle cell variant which seems to portray a mild/benign clinical phenotype of sickle cell disease.


Subject(s)
Anemia, Sickle Cell , Hemoglobinopathies , beta-Thalassemia , Adult , Anemia, Sickle Cell/genetics , Fetal Hemoglobin/analysis , Hemoglobin, Sickle/genetics , Hemoglobinopathies/diagnosis , Hemoglobinopathies/genetics , Humans , Male
18.
J Hum Rights Soc Work ; 6(4): 318-326, 2021.
Article in English | MEDLINE | ID: mdl-34150989

ABSTRACT

Somos Dign@s, a collective, composed by students, professors, and human rights activists, concerned about the crisis of human rights and civil liberties in Puerto Rico designed a successful national campaign for human rights known as: "Trayecto Dignidad" or "The Journey toward Dignity." This educational campaign emulated the Freedom Riders initiative of the 1960s. Throughout this article, we discuss the participatory action research (PAR) methodology designed by Somos Dign@s which frames the work of our Trayecto Dignidad campaign. Our methodology is based on the theoretical approaches of De Sousa-Santos (2002) and his conceptualization of human rights as having to rise through a process of "Globalization from below"; that is, a process of globalization that allows oppressed classes to advocate for their human rights. Five campaigns have been implemented since 2011. Some results have shown the need: (1) to continue educating about human and civil rights; (2) to educate and reinforce public policies to address discrimination based on race, social class, and gender particularly in the work setting; (3) to universalize health services; (4) to conduct a debt audit and advocate for the right of people of Puerto Rico to self-determination (UN Resolution 1514 XV); and (5) to integrate a public policy education based on gender perspective on schools and declare the State of Emergency for the femicides.

19.
Acad Pathol ; 8: 23742895211015347, 2021.
Article in English | MEDLINE | ID: mdl-34046523

ABSTRACT

In February of 2020, New York City was unprepared for the COVID-19 pandemic. Cases of SARS-CoV-2 infection appeared and spread rapidly. Hospitals had to repurpose staff and establish diagnostic testing for this new viral infection. In the background of the usual respiratory pathogen testing performed in the clinical laboratory, SARS-CoV-2 testing at the Montefiore Medical System grew exponentially, from none to hundreds per day within the first week of testing. The job of appropriately routing SARS-CoV-2 viral specimens became overwhelming. Additional staff was required to triage these specimens to multiple in-house testing platforms as well as external reference laboratories. Since medical school classes and many research laboratories shut down at the Albert Einstein College of Medicine and students were eager to help fight the pandemic, we seized the opportunity to engage and train senior MD-PhD students to assist in triaging specimens. This volunteer force enabled us to establish the "Pathology Command Center," staffed by these students as well as residents and furloughed dental associates. The Pathology Command Center staff were tasked with the accessioning and routing of specimens, answering questions from clinical teams, and updating ever evolving protocols developed in collaboration with a team of Infectious Disease clinicians. Many lessons were learned during this process, including how best to restructure an accessioning department and how to properly onboard students and repurpose staff while establishing safeguards for their well-being during these unprecedented times. In this article, we share some of our challenges, successes, and what we ultimately learned as an organization.

20.
Transfusion ; 61(4): 1064-1070, 2021 04.
Article in English | MEDLINE | ID: mdl-33665881

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a variable clinical course with significant mortality. Early reports suggested higher rates of SARS-CoV-2 infection in patients with type A blood and enrichment of type A individuals among COVID-19 mortalities. STUDY DESIGN AND METHODS: The study includes all patients hospitalized or with an emergency department (ED) visit who were tested for SARS-CoV-2 between March 10, 2020 and June 8, 2020 and had a positive test result by nucleic acid test (NAT) performed on a nasopharyngeal swab specimen. A total of 4968 patients met the study inclusion criteria, with a subsequent 23.1% (n = 1146/4968) all-cause mortality rate in the study cohort. To estimate overall risk by ABO type and account for the competing risks of in-hospital mortality and discharge, we calculated the cumulative incidence function (CIF) for each event. Cause-specific hazard ratios (csHRs) for in-hospital mortality and discharge were analyzed using multivariable Cox proportional hazards models. RESULTS: Type A blood was associated with the increased cause-specific hazard of death among COVID-19 patients compared to type O (HR = 1.17, 1.02-1.33, p = .02) and type B (HR = 1.32,1.10-1.58, p = .003). CONCLUSIONS: Our study shows that ABO histo-blood group type is associated with the risk of in-hospital death in COVID-19 patients, warranting additional inquiry. Elucidating the mechanism behind this association may reveal insights into the susceptibility and/or immunity to SARS-CoV-2.


Subject(s)
COVID-19/blood , COVID-19/mortality , Hospital Mortality , Hospitals , SARS-CoV-2/metabolism , ABO Blood-Group System , Aged , Aged, 80 and over , COVID-19/therapy , Disease-Free Survival , Female , Humans , Incidence , Male , Middle Aged , New York City/epidemiology , Retrospective Studies , Survival Rate
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