Insight into the complex pathophysiology of sickle cell anaemia and possible treatment

Sickle cell anaemia (SCA) is the consequence of abnormal haemoglobin production due to an inherited point mutation in the β‐globin gene. The resulting haemoglobin tetramer is poorly soluble when deoxygenated, and when this is prolonged, intracellular gelation of sickle haemoglobin occurs, followed by haemoglobin polymerisation. If many cycles of sickling and unsickling occur, the red cell membrane will be disrupted leading to haemolysis and vaso‐occlusive events. Recent studies have also shown that leucocyte adhesion molecules and nitric oxide (NO) depletion are involved in endothelial damage. New insights in SCA pathophysiology and vascular biology have shown that cell‐derived microparticle (MP) generation is also involved in the vaso‐occlusion. Endothelial damage is perpetuated by impaired production or increased consumption of protective modulators such as protein C, protein S and NO. New therapeutic interventions should address these aspects of SCA pathogenesis. To date, the only US‐FDA‐approved therapy to prevent painful vaso‐occulsive episodes is hydroxyurea that reduces haemoglobin polymerisation in sickle cells by increasing the production of foetal haemoglobin and L‐glutamine. However, several new drugs have been tested in the last years in randomised clinical trials. We here report an update on the current status of knowledge on SCA.     

Sensitivity to change and responsiveness of the Segmental Assessment of Trunk Control (SATCo) in children with spinal cord injury

Purpose: The purpose of this study was to assess the sensitivity and responsiveness of the Segmental Assessment of Trunk Control (SATCo) for evaluating trunk control in children with spinal cord injury (SCI) receiving activity-based locomotor training (AB-LT).

Methods: Prospective study of nine outcomes for consecutively enrolled children in outpatient AB-LT. To evaluate sensitivity to change, linear-mixed models were constructed and adjusted for covariates: age at and time since SCI. To evaluate responsiveness, standardized response means and 95% confidence intervals were estimated per outcome.

Results: SATCo scores increased significantly (p < 0.05) regardless of chronicity, initial score, and injury level. The SATCo was the most responsive measure and the only outcome demonstrating a large effect size after 3 months of therapy.

Conclusions: Children with SCI receiving AB-LT improved trunk control regardless of chronicity, initial impairment, or prior experience. SATCo sensitivity and responsiveness support its usefulness in measuring trunk control in children with SCI.     

The surgical anatomy of the sural nerve: An ultrasound study

The aim of this study was (a) to examine the anatomy of the sural nerve (SN) in a sample of 30 patients and (b) to analyze the incidence of different origins of the SN, and the distance of the SN from planned arthroscopic portals. An ultrasound (USG) examination of the SN was performed bilaterally on thirty healthy patients with no history of surgery or trauma of the lower limb. The SNs were classified into six main types of pattern, with an additional category for new and unclassified types. Each of Types 1 and 3 had two subdivisions. The distances from the superior border of the calcaneal tuberosity to the three simulated arthroscopy portal sites (Z1, Z1.5, Z2) to the SN were measured. A total of 30 patients (n = 60 limbs) with an average age of 27 ± 7.5 years were examined and the SN was visualized in all cases. The most common origin was Type 3A, accounting for 30% of limbs. Type 2 was the second most common seen in 18.3%. The distances of the SN from arthroscopic portal placement sites above the lateral malleolus were 2.07 ± 0.39 cm at the Z1 portal, 2.15 ± 0.38 cm at Z1.5, and 2.28 ± 0.33 cm at Z2. The variability in the anatomy of the SN warrants the use of USG to locate it accurately, thus preventing iatrogenic injury when portals are placed for arthroscopy, improving proper administration of anesthesia, and helping to localize the nerve for graft harvesting. Clin. Anat. 31:450–455, 2018. © 2017 Wiley Periodicals, Inc.     

Antigenotoxic properties of lactic acid bacteria in the S. typhimurium mutagenicity assay

A high percentage of human tumors is reported to be related to dietary habits. One way to improve the nutritional impact is to increase the intake of protective factors, such as inhibitors of DNA damage and other types of anticarcinogens. Specific strains of lactic acid bacteria used to ferment milk are promising candidates that may be antimutagenic and anticarcinogenic. We have studied the antimutagenicity of 10 isolated strains of beneficial lactic acid bacteria. Four types of fermented milk products were also studied for their protective properties. The effect of these bacteria on the yield of revertants induced by nitrosated beef extract was investigated in the Salmonella typhimurium mutagenicity assay. Eight of 10 isolated Lactobacillus strains reduced the yield of his+ revertants almost back to the levels of the untreated controls. Different fermented fresh yogurts containing viable bacteria (probably Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus or Lactobacillus acidophilus and Bifidobacteria) showed protective effects as well. The degree of suppressing revertants was independent of the yogurt's fat content. In contrast, yogurt products that had been heat treated were not inhibitory. The other fresh fermented milk products (e.g., buttermilk, kefir, and “Dickmilch”) were not antimutagenic in this study. The results imply that some bacteria used in milk processing have an antimutagenic potential and that this property is specific for the bacterial strain.