Russian “Successful” Clone B0/W148 of Mycobacterium tuberculosis Beijing Genotype: a Multiplex PCR Assay for Rapid Detection and Global Screening

We describe a multiplex PCR assay to detect the Mycobacterium tuberculosis Beijing genotype variant B0/W148, which is considered a “successful” clone of M. tuberculosis, widespread in Russia. Specificity and sensitivity of the assay were 100% based on the analysis of a collection of 516 M. tuberculosis isolates of different genotypes and origins. This assay may be used for accurate and simple detection and surveillance of this clinically and epidemiologically important variant of M. tuberculosis.     

Diagnostik und Therapie der ligamentären Ellenbogeninstabilitäten

Posttraumatic or acute instability of the elbow can develop after complete or incomplete dislocation of the elbow. Isolated medial collateral ligament ruptures can be a result of valgus trauma and lateral collateral ligament ruptures of pivot shift or varus trauma. Chronic instability of the elbow may occur after conservative or operative treatment of a traumatic ligament rupture without stable healing. Repetitive overuse in sports or professions may also cause chronic instability. This article provides the reader an overview about current concepts in elbow instability.     

Fully Integrated Artificial Pancreas in Type 1 Diabetes: Modular Closed-Loop Glucose Control Maintains Near Normoglycemia

Integrated closed-loop control (CLC), combining continuous glucose monitoring (CGM) with insulin pump (continuous subcutaneous insulin infusion [CSII]), known as artificial pancreas, can help optimize glycemic control in diabetes. We present a fundamental modular concept for CLC design, illustrated by clinical studies involving 11 adolescents and 27 adults at the Universities of Virginia, Padova, and Montpellier. We tested two modular CLC constructs: standard control to range (sCTR), designed to augment pump plus CGM by preventing extreme glucose excursions; and enhanced control to range (eCTR), designed to truly optimize control within near normoglycemia of 3.9-10 mmol/L. The CLC system was fully integrated using automated data transfer CGM→algorithm→CSII. All studies used randomized crossover design comparing CSII versus CLC during identical 22-h hospitalizations including meals, overnight rest, and 30-min exercise. sCTR increased significantly the time in near normoglycemia from 61 to 74%, simultaneously reducing hypoglycemia 2.7-fold. eCTR improved mean blood glucose from 7.73 to 6.68 mmol/L without increasing hypoglycemia, achieved 97% in near normoglycemia and 77% in tight glycemic control, and reduced variability overnight. In conclusion, sCTR and eCTR represent sequential steps toward automated CLC, preventing extremes (sCTR) and further optimizing control (eCTR). This approach inspires compelling new concepts: modular assembly, sequential deployment, testing, and clinical acceptance of custom-built CLC systems tailored to individual patient needs.     

Resistance of the sheep skull after a monocortical cranial graft harvest

IntroductionCranial bone grafts are commonly used for preimplant or facial reconstructive surgery. However, removing bone may weaken the parietal bone and lead to a loss of strength. This loss has never been quantified. Bone harvest site reconstruction is being carried out more frequently than in the past, but its effect on the strength of the donor site is unknown.The aim of our study is to quantify the loss of strength due to a monocortical cranial bone graft harvest in sheep.Materials and methodsThirty-four fresh sheep cadaver heads were used for the study. We performed a monocortical bone graft harvest on the posterior part of the right frontal bone. We used a surgical navigation system with optoelectronic tracking to measure bone thickness.To evaluate the resistance of the skull to an impact we developed a pendulum Charpy impact testing machine. The impact force hit a defined target frontal area.ResultsThe total thickness on both sides ranged from 3 mm to 10 mm with a mean of 6 mm (SD = 1.4 mm).The loss of strength between the intact left side and the harvested right side varied with a mean of 49% (SD = 17%) and was significant (p = 6.10^?10).ConclusionThis study has demonstrated that there is a loss of strength in the skull on the side where a bone graft has been harvested.Reconstruction of the harvested site using biomaterials reduces the poor aesthetic outcome due to depression at the site, but we do not know its effects on strength. This kind of study cannot be performed in humans for ethical reasons.Data obtained from this study will allow us to carry out a study in sheep to evaluate strength of the frontal area of a skull with a harvest site reconstructed with hydroxyapatite cement.     

Evaluation of 5‐Year Risk of Cardiovascular Events in Patients after Acute Myocardial Infarction Using Synchronization of 0.1‐Hz Rhythms in Cardiovascular System

Background: Synchronization between 0.1‐Hz rhythms in cardiovascular system is deteriorated at acute myocardial infarction (AMI) leading to a disruption of natural functional couplings within the system of autonomic regulation. Objective: This study evaluates the prognostic value of autonomic regulation indices for the 5‐year risk of fatal and nonfatal cardiovascular events in patients after AMI. Methods and Results: We studied 125 patients (53 [42%] female) after AMI aged between 30 and 83 years. The period of observation was 5 years with checkpoints at the first week after AMI and after each year after AMI. We compared the prognostic value of established clinical characteristics and degree S of synchronization between 0.1‐Hz rhythms in heart rate and microcirculation for evaluation of the 5‐year risk of mortality and recurrent myocardial infarction (MI) in patients after AMI. Acute heart failure Killip 2–4 at AMI and S < 20% at the first week after AMI were identified as the most important factors for evaluation of the risk of 5‐year mortality in patients after AMI (χ²= 14.2, P = 0.003). Sensitivity and specificity of low S (<20%) at the first week after AMI were 76% and 43%, respectively. For evaluation of the 5‐year risk of recurrent MI index S had no advantage over established clinical characteristics. Conclusion: The value of S below 20% in patients with AMI is a sensitive marker of high risk of mortality during the subsequent five years. It is characterized by better prognostic value than most of established clinical characteristics.     

Cysteine protease mcII-Pa executes programmed cell death during plant embryogenesis

Programmed cell death (PCD) is indispensable for eukaryotic development. In animals, PCD is executed by the caspase family of cysteine proteases. Plants do not have close homologues of caspases but possess a phylogenetically distant family of cysteine proteases named metacaspases. The cellular function of metacaspases in PCD is unknown. Here we show that during plant embryogenesis, metacaspase mcII-Pa translocates from the cytoplasm to nuclei in terminally differentiated cells that are destined for elimination, where it colocalizes with the nuclear pore complex and chromatin, causing nuclear envelope disassembly and DNA fragmentation. The cell-death function of mcII-Pa relies on its cysteine-dependent arginine-specific proteolytic activity. Accordingly, mutation of catalytic cysteine abrogates the proteolytic activity of mcII-Pa and blocks nuclear degradation. These results establish metacaspase as an executioner of PCD during embryo patterning and provide a functional link between PCD and embryogenesis in plants. Although mcII-Pa and metazoan caspases have different substrate specificity, they serve a common function during development, demonstrating the evolutionary parallelism of PCD pathways in plants and animals.