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Current prognostication in primary myelofibrosis (PMF) is based on the dynamic international prognostic scoring system (DIPSS)-plus, which employs clinical and cytogenetic variables. We recently reported DIPSS-plus independent prognostic significance for calreticulin ( CALR ) (favorable) and ASXL1 (unfavorable) mutations. In the current study, 570 PMF patients were recruited for derivation ( n =277) and validation ( n =293) of a molecular prognostic model based on these two mutations. Survival was the longest in CALR + ASXL1 − (median 10.4 years) and shortest in CALR − ASXL1 + patients (median, 2.3 years; hazard ratio (HR), 5.9; 95% confidence interval (CI), 3.5–10.0). CALR + ASXL1 + and CALR – ASXL1 − patients had similar survival and were grouped together in an intermediate-risk category (median survival, 5.8 years; HR, 2.5; 95% CI, 1.5–4.0). The CALR / ASXL1 mutations-based prognostic model was DIPSS-plus independent ( P <0.0001) and effective in identifying low-/intermediate-1-risk patients with shorter (median, 4 years) or longer (median 20 years) survival and high-/intermediate-2-risk patients with shorter (median, 2.3 years) survival. Multivariable analysis distinguished CALR − ASXL1 + mutational status as the most significant risk factor for survival: HR 3.7 vs 2.8 for age >65 years vs 2.7 for unfavorable karyotype. These observations signify immediate clinical relevance and warrant i) CALR and ASXL1 mutation determination in all patients with PMF and ii) molecular revision of DIPSS-plus.

The impact of calreticulin ( CALR ) mutations on long-term survival in essential thrombocythemia (ET) was examined in 299 patients whose diagnosis predated 2006. Mutational frequencies were 53% for Janus kinase 2 ( JAK2 ), 32% for CALR and 3% for MPL ; the remaining 12% were ‘triple-negative’. We confirmed the association of mutant CALR (vs JAK2 V617F) with younger age ( P =0.002), male sex ( P =0.01), higher platelet count (0.0004), lower hemoglobin ( P <0.0001), lower leukocyte count (0.02) and lower incidence of recurrent thrombosis (0.04). Triple-negative patients were also younger than their JAK2 -mutated counterparts ( P =0.003) and displayed lower hemoglobin ( P =0.003), lower leukocyte count (<0.0001) and lower thrombotic events ( P =0.02). Median follow-up time was 12.7 years and 47% of the patients were followed until death. Survival was the longest for triple-negative and shortest for MPL-mutated patients. Median survival was 19 years for JAK2 and 20 years for CALR-mutated cases ( P =0.32); the corresponding figures for patients of age ⩽65 years were 26 and 32 years ( P =0.56). The two mutational categories were also similar for leukemic ( P =0.28) and fibrotic ( P =0.28) progression rates. The current study is uniquely characterized by its very long follow-up period and provides accurate estimates of long-term survival in ET and complements current information on mutation-specific phenotype and prognosis.

The rapid growth in plastic consumption, particularly polyethylene terephthalate (PET), has led to a significant increase in plastic waste, posing a major environmental challenge. Developing an integrated circular economy framework for nanomaterial-enhanced recycled PET (nrPET) can be a promising approach to address this issue and advance sustainable and resilient road construction practices. This comprehensive review examines the current use of rPET in road construction, its existing limitations, and the role of nanomaterials in enhancing the performance of these materials. The review explores the mechanisms by which nanomaterials, such as carbon nanotubes, graphene, nanosilica, and clay nanoplatelets, can improve the properties of rPET, leading to more durable, weather-resistant, and cost-effective road materials. Furthermore, the review analyzes the environmental and sustainability benefits of using nrPET in road construction, focusing on carbon footprint reduction, conservation of natural resources, and alignment with circular economy principles. The potential for job creation, social benefits, and support for circular economy initiatives are also discussed. The review then delves into the challenges associated with the implementation of this framework, including technical barriers, economic and market barriers, regulatory and policy challenges, and environmental and safety considerations. Strategies to address these challenges, such as advancements in nanotechnology, scaling up circular economy models, and fostering collaborative research, are presented. Finally, the article proposes a framework and outlines future directions and research opportunities, emphasizing the exploration of emerging nanomaterials, scaling up circular economy models, and encouraging collaborations between researchers, industry stakeholders, policymakers, and communities.

Diabetes, one of the major global health emergencies of the 21st century, can affect a patient's quality of life. A compromised quality of life has adverse effects on self-care practices, resulting in inadequate glycemic control and an increased susceptibility to complications. In Ethiopia, there is a paucity of information regarding the quality of life of patients with type 2 diabetes mellitus. Therefore, this study aimed to assess health-related quality of life in type 2 diabetes mellitus patients. A cross-sectional study was conducted among type 2 diabetes mellitus patients attending diabetes follow-up clinics in selected public hospitals in Addis Ababa using short form- 36 (SF-36) health survey measures. Descriptive statistics were used to summarize the characteristics of the study participants. Simple and multiple linear regressions were done to identify significantly associated factors with health-related quality of life. A total of 309 patients participated in this study. The mean scores of the physical and mental component summaries were 40.15 (SD = 7.27) and 48.11 (SD = 8.87), respectively. Being old, being overweight or obese, living with type 2 diabetes mellitus for more than fifteen years, taking combined medication, having diabetes-related complications, and having comorbidities were factors that reduced the mean score of the physical component summary (p-value<0.05). Being obese and diabetes related complication were factors that negatively affect mental component summary (p-value <0.05). On the other hand, being married was factors that positively affect mental component summary (p-value <0.05). Older age, being married, obesity, overweight, longer duration of diabetes, using combined medications, diabetic-related complications, and co-morbidities were factors associated with health-related quality of life. Healthcare providers should strengthen counseling patients on lifestyle modifications such as diet modifications, and weight reduction.

Background: Poor adherence to antidiabetic medications leads to a higher rate of hospital admissions and adverse health outcomes in type 2 diabetes mellitus patients. Objective: This study aims to evaluate whether a pharmacist-led medication therapy management, compared to the usual care, could enhance medication adherence and reduce hospital admission in patients with type 2 diabetes mellitus. Methods: A prospective randomized controlled study was conducted in patients with type 2 diabetes mellitus from February 1 to July 30, 2016. Patients in the control group (n=65) received the usual care while patients in the intervention group (n=62) received a personalized pharmacotherapeutic care plan and diabetes education. The two groups were compared by repeated measure ANOVA at 3 and 6‐months with medication adherence (using Morisky medication adherence scale) and number of hospital admissions as the main outcome variables. Results: A total of 127 patients were included in the study. A marked and statistically significant increase in medication adherence from baseline to 3 and 6 months were noted in the intervention group (increased from 9.2% at baseline to 61% at 6 month) compared with the control group (increased from 13.2% at baseline (to 30.2% at 6 month; p-value<0.01). Furthermore, at the 6-month follow-up, only 23 patients in MTM group with poorly controlled blood glucose levels resulted in hospital admissions compared to 48 patients in non-MTM group, resulting in a 52.1% fewer hospital admissions (p< 0.001). Conclusions: The findings of this study implied that pharmacist-led medication therapy management might improve medication adherence and reduce number of hospitalizations in patients with type 2 diabetes mellitus. Hence, policies and guidelines should be in place in order for clinical pharmacists to fully engage in patient care and improve the medication therapy outcomes.

DFs originating in leprosy lesions were considered when the histological sections clearly showed the DF inserted in the context of a leprosy lesion in regression in the adjacent tissues. Clinical data (sex, age, location of DF, classification of leprosy and leprosy reactions, time between the leprosy and DF diagnoses, and treatment of leprosy reactions) were retrieved through the review of medical records. Fig. 1 Representative panel of dermatofibroma originating in a leprosy lesion: a, c, e, and g Hematoxylin-eosin-stained histological section showing the dermatofibroma in the center (light arrows) and the leprosy lesion in regression at the periphery (dark arrows); b, d, f, and h histological section for bacilloscopy (Fite-Faraco) showing absence of bacilli in the dermatofibroma (clear arrows) and presence of fragmented bacilli in the leprosy lesion in peripheral regression (dark arrows); i, j, k, l basic immunohistochemical panel – expression of anti-CD68 (i) in leprosy lesion macrophages and the absence of anti-factor XIIIa expression in the same macrophages (j); the absence of anti-CD68 expression (k) and the expression of anti-factor XIIIa in dermatofibroma cells Numeric variables are described as the mean (SD) or median (interquartile range) according to the normality of their distribution, and categorical data are described as the frequency/percentage. Body location of DF Leprosy patients with DF, count (%) Non-leprosy patients with DF, count (%) Total Cervical 0 (0%) 1 (0.5%) 1 Face 0 (0%) 2 (1.0%) 2 Thorax 0 (0%) 9 (4.7%) 9 Abdomen 0 (0%) 1 (0.5%) 1 Dorsum 4 (13.3%) 27 (14.1%) 31 Thigh 10 (33.3%) 35 (18.2%) 45 Arm 7 (23.3%) 31 (16.1%) 38 Hand 1 (3.3%) 5 (2.6%) 6 Buttock 1 (3.3%) 1 (0.5%) 2 Knee 2 (6.7%) 2 (1.0%) 4 Forearm 1 (3.3%) 21 (10.9%) 22 Leg 9 (30.0%) 54 (28.1%) 63 Elbow 1 (3.3%) 9 (4.7%) 10 Shoulder 0 (0%) 5 (2.6%) 5 Foot 1 (3.3%) 4 (2.1%) 5 Perineum 0 (0%) 1 (0.5%) 1 Total 30 192 222 All DFs in RLLs were common DFs, and three of them had the histologic patterns characteristic of the atrophic variant.

Ankylosing spondylitis (AS) represents a chronic inflammatory bone disease of the axial skeleton that manifests as chronic back pain and progressive stiffness of the spine. It characteristically affects young adults with a peak age of onset between 20–30 years. In contrast to Western Europe and North America, the disease is rare in Sub-Saharan Africa where the majority of the population is HLA-B27 negative. Even in some African populations where HLA-B27 is prevalent (for example, in Gambia and Senegal, where 3–6% of the general population has HLA-B27), the disease is also said to be rare. However, some other genetic markers may be involved in the causation of AS in the HLA-B27 negative population, and when it occurs in this subgroup of patients it has a similar manifestation with HLA-B27 negative white patients and these patients rarely develop anterior uveitis. The clinical presentation of the disease in Africa is generally milder; most affected individuals do not have a family history of AS, the patients are older at onset of the disease, and the majority of them lack extra-articular manifestations such as anterior uveitis compared with the situation in Western Europe and North America. In conclusion, AS in sub-Saharan Africa seems to represent a subgroup of the disease, which may open the window to a greater understanding of the pathophysiology of the condition.

Purpose Racial disparities are evident in colorectal cancer (CRC) prognosis with black patients experiencing worse outcomes than Hispanics and whites, yet mediators of these disparities are not fully known. The aim of this study is to identify variables that contribute to racial/ethnic disparities in health-related quality of life (HR-QoL) and overall survival in CRC. Methods Using SF-12 questionnaires, we assessed HR-QoL in 1132 CRC patients by calculating their physical (PCS) and mental composite summary (MCS) scores. Associations between poor PCS/MCS and sociodemographic factors were estimated and survival differences were identified by race/ethnicity. Results Hispanic patients who never married were at greater risk of poor PCS (OR 2.69; 95% CI 1.11–6.49; P  = 0.028) than were currently married patients. College education was associated with a decreased risk of poor PCS in Hispanic and white, but not black, patients. Gender was significantly associated with poor MCS among white patients only. CRC patients who reported a poor PCS or MCS had poor survival, with differences in median survival times (MSTs) by race. The effect of PCS was strongest in white CRC patients with a difference in overall MST of > 116 months between those with favorable versus poor physical HR-QoL. Black patients who reported poor Physical and Mental HR-QoL showed significant risk of a poor outcome. Conclusion These findings suggest that racial/ethnic disparities in CRC survival may be related to differences in HR-QoL. Identified mediators of HR-QoL could supplement current CRC management strategies to improve patients’ survival.