Physical growth in thalassemic children of 2-12 years with multiple transfusions

The hemoglobinopathies are the most common single-gene defect in man. The thalassemia syndromes are a heterogeneous group of hereditary disorder due to decreased synthesis of either α or β globin chain of Hb A. There are 3 phases of growth disturbances and have three different etiologies. First phase: growth disturbances is mainly due to hypoxia, anaemia, ineffective erythropoiesis and nutritional factors; the Second phase: During late childhood, growth retardation is mainly due to iron overload affecting the GH-IGF-1 axis and other endocrinal complications. Third phase: after the age of 10-11 years, delayed or arrested puberty is an important contributory factor to growth failure in adolescents thalassemic who does not show any growth spurt. Cross-sectional, observational, single-centre, tertiary hospital-based study. Children of thalassemia major of 2-12 years with multiple transfusions was taken over 1 year. Study population was divided into 2 groups: Group1-irregularly transfused; Group 2-regularly transfused. Clinical settings, anthropometry, laboratory tests like serum ferritin, pre-transfusion haemoglobin, total leucocyte count etc. were taken into consideration. Thalassemia children with other comorbidities like tuberculosis, chronic kidney disease, chronic heart diseases etc. were excluded from the study.Among the 200 children, 143 (71.5%) were taking regular (2-4 weekly) transfusion therapy and 57 (28.5%) were taking irregular transfusion (>4weekly). Mean age of diagnosis was 18.66 ± 7.443months in Group 1 (Irregularly transfused) and 18.93 ± 7.218 months in Group 2 (Regularly transfused). Among the regularly transfused thalassemic 17.7% children had W/A < 3 percentile and among the irregularly transfused children it was 15%. Among the irregularly transfused children, 27. 1% and among the regularly transfused children 21.6% had H/A <3rd percentile. In the present study children 61% had normal BMI and only 5.4 % had BMI less than 3rd percentile overall. Among irregularly transfused thalassemic children >10years of age, 86.7% have not attained puberty yet. Among the regularly transfused thalassemic children 96.7% have not attained puberty yet. US and LS individually affected resulting in stunting but it was proportionate innature so US: LS ratio was according to age. A positive correlation between pre-transfusion haemoglobin and W/A and H/A suggested that with decreasing pre-transfusion haemoglobin concentration more child had growth retardation. Mean value of serum Ferritin was 941 ± 608.490 ng/ml in Group 1(Irregularly transfused) and Mean value of serum Ferritin was 1403 ± 685.584ng/ml in Group 2(Regularly transfused). MUAC in the present study was 12.44cm suggesting mild-moderate malnutrition. Extremely variable clinical and haematological findings were observed in these patients. Growth retardation has found in both regularly and irregularly transfused patients. These findings are almost comparable to other Indian studies. Appropriate knowledge regarding prenatal counselling, early diagnosis, regular transfusions and overall treatment can help better management of this group of patients.

The Deleterious Effects of Impaired Fibrinolysis on Skeletal Development Are Dependent on Fibrin(ogen), but Independent of Interlukin-6

Chronic diseases in growing children, such as autoimmune disorders, obesity, and cancer, are hallmarked by musculoskeletal growth disturbances and osteoporosis. Many of the skeletal changes in these children are thought to be secondary to chronic inflammation. Recent studies have likewise suggested that changes in coagulation and fibrinolysis may contribute to musculoskeletal growth disturbances. In prior work, we demonstrated that mice deficient in plasminogen, the principal protease of degrading and clearing fibrin matrices, suffer from inflammation-driven systemic osteoporosis and that elimination of fibrinogen resulted in normalization of IL-6 levels and complete rescue of the skeletal phenotype. Given the intimate link between coagulation, fibrinolysis, and inflammation, here we determined if persistent fibrin deposition, elevated IL-6, or both contribute to early skeletal aging and physeal disruption in chronic inflammatory conditions. Skeletal growth as well as bone quality, physeal development, and vascularity were analyzed in C57BL6/J mice with plasminogen deficiency with and without deficiencies of either fibrinogen or IL-6. Elimination of fibrinogen, but not IL-6, rescued the skeletal phenotype and growth disturbances in this model of chronic disease. Furthermore, the skeletal phenotypes directly correlated with both systemic and local vascular changes in the skeletal environment. In conclusion, these results suggest that fibrinolysis through plasmin is essential for skeletal growth and maintenance, and is multifactorial by limiting inflammation and preserving vasculature.

An adaptive super-twisting algorithm based on conditioning technique

This paper presents an adaptive conditioning-technique-based super-twisting algorithm aiming at improving the convergence speed and reducing the overshoot at the same time. Compared with a recently proposed method called new modified super-twisting algorithm, in which a linear acceleration factor and a damping factor are added to achieve this goal, the proposed method has several advantages. First, the proposed method enhances the convergence performance of the system by resorting to the characteristics of the conditioned super-twisting algorithm and the adaptive gains, without changing the basic structure of the classical super-twisting controller. Thus, stability proof of this method is much simpler and more concise. Furthermore, unlike the new modified super-twisting algorithm, in which an unnatural assumption on the Lipschitz disturbance is made for the stability proof, this method can counteract not only typical bounded Lipschitz disturbances but also square-root growth disturbances. Also, a set of less conservative control gains can be obtained with the proposed algorithm than with the compared algorithm. Apart from these benefits, several simulation results illustrate that the performance of the proposed method is even better in convergence and recovering from disturbance.

Mosaic Segmental and Whole-Chromosome upd(11)mat in Silver-Russell Syndrome

Molecular defects altering the expression of the imprinted genes of the 11p15.5 cluster are responsible for the etiology of two congenital disorders characterized by opposite growth disturbances, Silver–Russell syndrome (SRS), associated with growth restriction, and Beckwith–Wiedemann syndrome (BWS), associated with overgrowth. At the molecular level, SRS and BWS are characterized by defects of opposite sign, including loss (LoM) or gain (GoM) of methylation at the H19/IGF2:intergenic differentially methylated region (H19/IGF2:IG-DMR), maternal or paternal duplication (dup) of 11p15.5, maternal (mat) or paternal (pat) uniparental disomy (upd), and gain or loss of function mutations of CDKN1C. However, while upd(11)pat is found in 20% of BWS cases and in the majority of them it is segmental, upd(11)mat is extremely rare, being reported in only two SRS cases to date, and in both of them is extended to the whole chromosome. Here, we report on two novel cases of mosaic upd(11)mat with SRS phenotype. The upd is mosaic and isodisomic in both cases but covers the entire chromosome in one case and is restricted to 11p14.1-pter in the other case. The segmental upd(11)mat adds further to the list of molecular defects of opposite sign in SRS and BWS, making these two imprinting disorders even more specular than previously described.

Dendrogeomorphology of Different Landslide Types: A Review

The dating of past landslide events is one of the most crucial aspects of landslide research, leading to a better understanding of past landslide activity. Landslides can be extremely dangerous natural hazards, and thus, solving the relationships between their activity and climate variations is of high importance. For these purposes, data about past landslide activity are fundamental for such analyses. Various methods of landslide absolute dating exist, but the most precise approach that dates back several centuries is based on tree-ring analysis (dendrogeomorphology). Landslide movements can affect the growth of trees in response to specific growth disturbances. Although dendrogeomorphic methods are successfully used for dating other geomorphic processes, their use in landslide research is actually the most frequent. Dendrogeomorphic research on landslides is strongly influenced by general approaches of landslide signal extraction from tree-ring series of disturbed trees and by the type of landslide (varying by morphology, material and mechanism of movement). This study provides an overview of basic aspects of dendrogeomorphic research on landslides, and more specifically, it reviews basic tree-ring-based approaches of landslide dating. Presented review focuses on various landslide types and their effect on dendrogeomorphic dating. This review is built from the extensive database of all accessible dendrogeomorphic studies of landslides from 1893 to 2020. Moreover, recommendations for specific sampling and approach choice in individual landslide types are presented. Finally, limits of tree-ring-based approaches are presented, including provided proposals for further research.

Dual support technique for pediatric palatal fracture: 1.5 mm transmucosal titanium plates along with acrylic splint backing

Surgeons are always in a dilemma for the management of paediatric facial fractures due to distinctive nature of growing facial skeleton. The ultimate treatment goal for paediatric fractures should be as conservative as possible with least invasive surgical approach that will access the fracture and least invasive surgical fixation that will allow stable reduction and will prevent any growth disturbances. We are presenting a case of 4- year old with panfacial fracture managed according to this principle using transmucosal titanium plates with acylic splint for sagittal split of palate.