Knowledge and self-care practice regarding diabetes among type 2diabetics: experience from a non-profit hospital chain in Bangladesh

Diabetes mellitus (DM) is generally being perceived as a problem of the developed world, but currently, people from developing countries like Bangladesh are suffering from chronic diseases of which diabetes is a major one. The aim of the study was to assess knowledge and self-care practice regarding diabetes among type 2 diabetes mellitus (T2DM) subjects. A cross-sectional study was conducted among 11,917 (age ≥?18 years, 4418 males and 7499 females) T2DM subjects attending the health care centers and hospitals in Dhaka (Capital) and also in the northern part of Bangladesh operated by the local diabetic association. Data were collected through interviewer-administered questionnaire. The levels of knowledge and self-care practice were measured by predefined scores, categorized as poor (<mean – 1 SD), average (mean?±?1 SD), and good (>mean?+?1 SD). Independent samples t test, ANOVA, and Pearson’s correlation were used to determine the association between different variables considering p value <?0.05. The mean (± SD) age (years) of the T2DM was 50?±?12. The proportion of “poor,” “average,” and “good” score for knowledge were 34%, 51%, and 15% and for that practice were 16%, 72%, and 12%, respectively. Knowledge was significantly associated with practice (r?=?0.299, p?=?0.001). The study reveals a difference between knowledge and self-care practice related to T2DM. T2DM health literacy program needs to be developed for better health promotion.     

Histiocytosis X in children: Patterns of disease and results of treatment

The pathologic materials and clinical courses of 36 children aged 1 month-22 years, with histiocytosis × (H-X) seen at the Philadelphia Children's Cancer Research Center from 1970 to 1979 were reviewed. The pathologic subtype of H-X was favorable (type II) in 31 patients, unfavorable (type I) in one patient, and unclassified in four patients whose specimens were limited to a skin biopsy. Sixteen patients had localized H-X involving bone (14 patients), soft tissue (1 patient), or skin only (1 patient); all are alive and well after treatment with surgery alone (12 patients), radiation therapy (RT) (3 patients), or observation (1 patient); only 1 of the 16 developed recurrent H-X. The other 20 patients presented with multifocal H-X involving the skeleton alone (3 patients); the skeleton and soft tissues other than liver (7 patients); soft tissue exclusive of the liver (3 patients); soft tissue including the liver (4 patients); or soft tissues, skeleton, and liver or multiple drugs ± RT (15 patients). Seven of the 20 patients are alive and well without recurrence at a median of 4 years after diagnosis. Nine of the 20 patients, including 3 with liver dysfunction, responded completely to initial therapy but developed recurrence; each was retreated with drugs and is alive and well at a median of 4 years. The remaining 4 patients had widespread disease with dysfunction of the liver and/or hematopoietic system at diagnosis, failed to respond, and died. We conclude that (1) patients with multiple bony lesions with or without associated soft tissue disease or skin involvement have a favorable outlook and do not require systemic chemotherapy; (2) systemic treatment also is unnecessary for patients with localized H-X since recurrence is rare; (3) drugs can benefit patients with multifocal H-X, although the optimal duration of therapy is unclear; and (4) favorable response to treatment indicates high probability of disease-free survival. However, organ dysfunction at diagnosis is ominous: four of seven patients with liver dysfunction are dead, as are all three patients who prsented with peripheral blood count depression.     

Head and neck cancer: the pursuit of molecular diagnostic markers

From a histopathologic perspective, head and neck squamous cell carcinoma (HNSCC) is a relatively straightforward diagnosis. However, the clinically useful information presently provided by pathologists is embarrassingly limited. Similarly, our ability to accurately identify the earliest premalignant lesions as well as predict which premalignant lesions are likely to progress to HNSCC is limited. Over the last decade, an explosive growth of knowledge related to the molecular biology of this disease has occurred, which is now being used to address these issues. For example, we now appreciate that there are multiple etiologies and multiple molecular mechanisms responsible for the development of HNSCC. New techniques have improved our ability to identify molecularly premalignant, but histologically benign lesions. Similarly, recent studies have been able to predict which premalignant lesions are likely to progress to HNSCC. In addition to having utility in the realm of early diagnosis, molecular diagnostics may have a profound impact on how we diagnose and report HNSCC. While still in the developmental stage, molecular protocols are being used to evaluate surgical margins, determine the location of unknown primary tumors, identify histologically undetectable lymph node metastasis, and predict which tumors are more likely to respond to a particular postsurgical adjuvant therapy.     

Antigen-targeted liposome-encapsulated methotrexate specifically kills lymphocytes sensitized to the nonapeptide of myelin basic protein

Antigen targeting of liposome-encapsulated cytotoxic drugs to specific lymphocytes may be a useful approach for antigen-specific immunosuppressive treatment of autoimmune diseases in which a specific antigen is involved. The feasibility of utilizing this approach was investigated using experimental allergic encephalomyelitis as an animal model for an autoimmune response. The encephalitogenic determinant of myelin basic protein for the guinea pig is contained in residues 114-122, the so-called nonapeptide. We have acylated the nonapeptide at its N-terminal to anchor it in the lipid bilayer of liposomes containing the cytotoxic drug methotrexate. The nonapeptide on the surface of the liposomes then allows targeting of the liposomal methotrexate in vitro to anti-nonapeptide T lymphocytes obtained from guinea pigs with experimental allergic encephalomyelitis. Treatment with the nonapeptide-targeted liposomal methotrexate inhibited proliferation of anti-nonapeptide lymphocytes significantly more than that of control lymphocytes. These included non-sensitized lymphocytes, stimulated with phytohemagglutinin, or lymphocytes sensitized to different, unrelated proteins, the purified protein derivative of tuberculin and keyhole limpet hemocyanin, and stimulated with their specific antigens. Furthermore, nonapeptide-targeted liposomes had a greater cytotoxic effect on anti-nonapeptide T cells than untargeted liposomes. The results indicated that specific targeting to and killing of anti-nonapeptide cells was achieved, although improvements of the treatment are necessary before its use can be attempted in vivo.     

Increased transforming growth factor beta 1 expression mediates ozone-induced airway fibrosis in mice

Ozone (O?), a commonly encountered environmental pollutant, has been shown to induce pulmonary fibrosis in different animal models; the underlying mechanism, however, remains elusive. To investigate the molecular mechanism underlying O?-induced pulmonary fibrosis, 6- to 8-week-old C57BL/6 male mice were exposed to a cyclic O? exposure protocol consisting of 2 days of filtered air and 5 days of O? exposure (0.5 ppm, 8 h/day) for 5 and 10 cycles with or without intraperitoneal injection of IN-1233, a specific inhibitor of the type 1 receptor of transforming growth factor beta (TGF-β), the most potent profibrogenic cytokine. The results showed that O? exposure for 5 or 10 cycles increased the TGF-β protein level in the epithelial lining fluid (ELF), associated with an increase in the expression of plasminogen activator inhibitor 1 (PAI-1), a TGF-β-responsive gene that plays a critical role in the development of fibrosis under various pathological conditions. Cyclic O? exposure also increased the deposition of collagens and alpha smooth muscle actin (α-SMA) in airway walls. However, these fibrotic changes were not overt until after 10 cycles of O? exposure. Importantly, blockage of the TGF-β signaling pathway with IN-1233 suppressed O?-induced Smad2/3 phosphorylation, PAI-1 expression, as well as collagens and α-SMA deposition in the lung. Our data demonstrate for the first time that O? exposure increases TGF-β expression and activates TGF-β signaling pathways, which mediates O?-induced lung fibrotic responses in vivo.     

COVID-19 vaccine effectiveness by HIV status and history of injection drug use: a test-negative analysis

Introduction

People living with HIV (PLWH) and/or who inject drugs may experience lower vaccine effectiveness (VE) against SARS-CoV-2 infection.

Methods

A validated algorithm was applied to population-based, linked administrative datasets in the British Columbia COVID-19 Cohort (BCC19C) to ascertain HIV status and create a population of PLWH and matched HIV-negative individuals. The study population was limited to individuals who received an RT-PCR laboratory test for SARS-CoV-2 between 15 December 2020 and 21 November 2021 in BC, Canada. Any history of injection drug use (IDU) was ascertained using a validated administrative algorithm. We used a test-negative study design (modified case−control analysis) and multivariable logistic regression to estimate adjusted VE by HIV status and history of IDU.

Results

Our analysis included 2700 PLWH and a matched population of 375,043 HIV-negative individuals, among whom there were 351 and 103,049 SARS-CoV-2 cases, respectively. The proportion of people with IDU history was much higher among PLWH compared to HIV-negative individuals (40.7% vs. 4.3%). Overall VE during the first 6 months after second dose was lower among PLWH with IDU history (65.8%, 95% CI = 43.5–79.3) than PLWH with no IDU history (80.3%, 95% CI = 62.7–89.6), and VE was particularly low at 4–6 months (42.4%, 95% CI = −17.8 to 71.8 with IDU history vs. 64.0%; 95% CI = 15.7–84.7 without), although confidence intervals were wide. In contrast, overall VE was 88.6% (95% CI = 88.2–89.0) in the matched HIV-negative population with no history of IDU and remained relatively high at 4–6 months after second dose (84.6%, 95% CI = 83.8–85.4). Despite different patterns of vaccine protection by HIV status and IDU history, peak estimates were similar (≥88%) across all populations.

Conclusions

PLWH with a history of IDU may experience lower VE against COVID-19 infection, although findings were limited by a small sample size. The lower VE at 4–6 months may have implications for booster dose prioritization for PLWH and people who inject drugs. The immunocompromising effect of HIV, substance use and/or co-occurring comorbidities may partly explain these findings.     

Angiopoietin 2 Is Associated with Vascular Necroptosis Induction in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome

Vascular injury is a well-established, disease-modifying factor in acute respiratory distress syndrome (ARDS) pathogenesis. Recently, coronavirus disease 2019 (COVID-19)–induced injury to the vascular compartment has been linked to complement activation, microvascular thrombosis, and dysregulated immune responses. This study sought to assess whether aberrant vascular activation in this prothrombotic context was associated with the induction of necroptotic vascular cell death. To achieve this, proteomic analysis was performed on blood samples from COVID-19 subjects at distinct time points during ARDS pathogenesis (hospitalized at risk, N = 59; ARDS, N = 31; and recovery, N = 12). Assessment of circulating vascular markers in the at-risk cohort revealed a signature of low vascular protein abundance that tracked with low platelet levels and increased mortality. This signature was replicated in the ARDS cohort and correlated with increased plasma angiopoietin 2 levels. COVID-19 ARDS lung autopsy immunostaining confirmed a link between vascular injury (angiopoietin 2) and platelet-rich microthrombi (CD61) and induction of necrotic cell death [phosphorylated mixed lineage kinase domain-like (pMLKL)]. Among recovery subjects, the vascular signature identified patients with poor functional outcomes. Taken together, this vascular injury signature was associated with low platelet levels and increased mortality and can be used to identify ARDS patients most likely to benefit from vascular targeted therapies.

For decades, vascular injury has been recognized as a key element in the pathogenesis of acute respiratory distress syndrome (ARDS).¹ However, this has not translated into vascular targeted therapies for ARDS. This may, in part, be related to heterogeneity in the vascular response to injury among ARDS subjects, as well as to difficulty in selecting patients most at risk for ARDS vascular injury. Blood proteomics has been proposed as a novel translational approach to better match patients to precision therapies for ARDS.² A better understanding of the blood proteomic changes associated with ARDS vascular injury could therefore help identify patients likely to benefit from vascular therapies.Previous targeted studies of circulating vascular proteins have greatly enhanced the understanding of ARDS vascular injury. For example, measurement of the plasma angiocrine factor angiopoietin 2 (ANGPT2) in patients at the early stages of ARDS demonstrates that vascular injury likely precedes mechanical ventilation³ and is associated with ARDS disease mortality.⁴ However, these ANGPT2-mediated vascular disruptions can be countered. In mice, systemic administration of platelet-derived pericyte chemokines, such as angiopoietin 1 (ANGPT1) and platelet-derived growth factor B (PDGFB), counter ANGPT2-mediated vascular disruption, demonstrating the homeostatic potential of the blood vascular proteome.⁵ Improved understanding of the blood proteomic changes in subjects with ARDS with high or low vascular injury can build on these prior observations, shed further light onto disease pathogenesis, and identify protein targets for further investigation.More recently, vascular injury has been associated with coronavirus disease 2019 (COVID-19) ARDS,^6,7 including the vascular complications of inflammation and thrombosis. In this context, COVID-19–induced injury to the vascular compartment has been associated with complement activation and microvascular thrombosis,8, 9, 10 systemic thrombosis,^9,11 and dysregulated immune responses.^12,13 However, this focus on inflammation and thrombosis limits our insights into other disruptions associated with aberrant vascular activation, including angiogenesis, junctional barrier integrity, the role of activated platelets in vascular injury, and induction of vascular cell death, including specialized receptor-interacting protein kinase 3 (RIPK3)–mediated necrotic cell death. Specifically, although ANGPT2-mediated vascular disruption has been documented in COVID-19,¹⁴ the association between ANGPT2 and induction of vascular cell death remains largely unexplored in ARDS investigations.The purpose of this study was to assess whether aberrant vascular activation in COVID-19 was associated with the induction of necroptotic vascular cell death. To this aim, blood proteomics was performed in three independent COVID-19 cohorts, which enrolled patients at distinct time points in disease pathogenesis and included non–COVID-19 ARDS samples as control. Protein expression was linked to relevant clinical outcomes, vascular injury, and cell death markers in COVID-19 autopsy lung tissue.