Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation

Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3⁺CD19⁺ cell depletion (CD3/19D) versus CD34⁺ selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios^? FoxP3⁺Treg reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.     

Safety and Efficacy of Setarud (IMOD TM ) Among People Living with HIV/AIDS: A Review

The broad use of highly active anti-retroviral therapy (HAART), especially in developing world, has been associated with several problems such as lactic acidosis, lipodistrophy, pancreatitis, hyperlipidemia, insulin resistance and hepatotoxicity. Extensive use of HAART has also resulted in emergence of resistant HIV variants. Thereby, a pressing need for development of novel and cost-effective agents arises from these limitations. Setarud (IMODTM) is a safe, naturally- derived immunomodulator that was introduced for treatment of HIV patients in Iran. It is prepared as a mixture of herbal extracts including Tanacetum vulgare (tansy), Rosa canina and Urtica dioica (nettle) in addition to selenium, flavonoids and carotenes. Tanacetum vulgare may relieve anti-inflammatory symptoms and Rosa canina defers blood glucose and cholesterol elevation. Extracts from Urtica dioica may prevent maturation of myeloid dendritic cells and reduce T cell responses. A significant rise of CD4 count was observed in HIV patients treated by IMODTM in clinical trial phases, which could be explained by its immunomodulatory effects. Anti-oxidative activity of compounds in IMODTM might play a role in the clinical outcomes of patients treated with this drug. Moreover, IMODTM may show improving activity upon lipid profile and liver metabolism. According to studies on IMODTM, it seems that IMODTM has minor side effects. IMODTM with international publication number WO 2007/087825 A1 is an herbal extract which includes Rosa canina, Urtica dioica, Tanacetum vulgare, and selenium comprising a treatment by pulsed electromagnetic field of high frequency and is useful in treatment of HIV infection and AIDS.     

Evaluation of CD11b expression on peripheral blood neutrophils for early detection of neonatal sepsis

Neonatal sepsis is a disease of infants who are less than 1 month of age. These infants are clinically ill, and their blood culture are positive for bacteria. The reported incidence of neonatal sepsis for all infants is 1 to 10 per 1000 live births. The mortality rate is 4.2-26%. The clinical signs are not specific and diagnosis of neonatal sepsis is one of the most difficult tasks in clinical medicine. The aim of this work was determination of CD11b sensitivity and specificity for early detection of neonatal sepsis. We studied 65 neonates with gestational age of 27 to 38 weeks who were suspected for sepsis within the 28 days of life. Whole blood was obtained from neonates to determine CD11b expression on peripheral blood neutrophils by flow cytometry. C-Reactive protein (CRP) was measured qualitatively. Neonates were divided into two groups. Classification was based on the result of the blood culture. In the sepsis group all of the neonates (n=8) showed positive blood culture and clinical symptoms. In the suspected group (n=57) the neonates showed clinical signs but blood cultures were negative. Sensitivity and specificity of CD11b were 75%, 100% respectively. Also positive and negative predictive values of CD11b were 100% and 86% respectively. Results of present study and previous studies showed that measurement of neutrophil surface markers can be useful for diagnosis of infection in the early phases. Also, the quantitative measurement of CRP in addition to CD11b further enhances the ability to diagnose infections and improves sensitivity and negative predictive value by 100%.     

The anatomy and development of the claws of Xenopus laevis (Lissamphibia: Anura) reveal alternate pathways of structural evolution in the integument of tetrapods

Digital end organs composed of hard, modified epidermis, generally referred to as claws, are present in mammals and reptiles as well as in several non-amniote taxa such as clawed salamanders and frogs, including Xenopus laevis . So far, only the claws and nails of mammals have been characterized extensively and the question of whether claws were present in the common ancestor of all extant tetrapods is as yet unresolved. To provide a basis for comparisons between amniote and non-amniote claws, we investigated the development, growth and ultrastructure of the epidermal component of the claws of X. laevis . Histological examination of developing claws of X. laevis shows that claw formation is initiated at the tip of the toe by the appearance of superficial cornified cells that are dark brown. Subsequent accumulation of new, proximally extended claw sheath corneocyte layers increases the length of the claw. Histological studies of adult claws show that proliferation of cornifying claw sheath cells occurs along the entire length of the claw-forming epidermis. Living epidermal cells that are converting into the cornified claw sheath corneocytes undergo a form of programmed cell death that is accompanied by degradation of nuclear DNA. Subsequently, the cytoplasm and the nuclear remnants acquire a brown colour by an as-yet unknown mechanism that is likely homologous to the colouration mechanism that occurs in other hard, cornified structures of amphibians such as nuptial pads and tadpole beaks. Transmission electron microscopy revealed that the cornified claw sheath consists of parallel layers of corneocytes with interdigitations being confined to intra-layer contacts and a cementing substance filling the intercorneocyte spaces. Together with recent reports that showed the main molecular components of amniote claws are absent in Xenopus , our data support the hypothesis that claws of amphibians likely represent clade-specific innovations, non-homologous to amniote claws.     

A rare case of multiple talon cusps in three siblings

Talon cusp is an uncommon anomaly, whose etiology may be disturbances in the morphodifferentiation stage. Dens in dente is also a rare anomaly that is challenging in clinic as it may cause pulp necrosis or periapical lesions due to the communication with the oral cavity. This article reports multiple talon cusps on permanent maxillary and mandibular incisors and molars in 3 siblings. A 9-year-old boy presented with structures like nodules, shaped as cylindrical cones with a sharp point or a raindrop with deep developmental fissures on the palatal aspect of the maxillary central incisors, lingual aspect of the mandibular central incisors and labial aspect of both mandibular first molars. The buccal surface of the maxillary right central incisor was also affected. Some of them exhibited dens in dente. His 15-year-old sister had prominent talon cusps on the palatal surface of maxillary central incisors and buccal surface of the mandibular first molars and mandibular left second molar. His 7-year-old brother had only one trace talon on the maxillary left central incisor. No syndrome was identified in the patients. In conclusion, genetic inheritance may be a causative factor in talon cusp.     

Sentinel chicken seroconversions track tangential transmission of West Nile virus to humans in the greater Los Angeles area of California

In Los Angeles, California, West Nile virus (WNV) has followed a pattern of emergence, amplification, subsidence, and resurgence. A time series cross-correlation analysis of human case counts and sentinel chicken seroconversions revealed temporal concordance indicating that chicken seroconversions tracked tangential transmission of WNV from the basic passeriform-Culex amplification cycle to humans rather than antecedent enzootic amplification. Sentinel seroconversions provided the location and time of transmission as opposed to human cases, which frequently were reported late and were assumed to be acquired 2-14 days before disease onset at their residence. Cox models revealed that warming degree-days were associated with the increased risk of seroconversion, whereas elevated herd immunity in peridomestic birds dampened seroconversion risk. Spatially, surveillance data collected within a 5 km radius of flock locations 15-28 days before the bleed date were most predictive of a seroconversion. In urban Los Angeles, sentinel chicken seroconversions could be used as an outcome measure in decision support for emergency intervention.     

Circular External Fixation Frames with Divergent Half Pins: A Pilot Biomechanical Study

The use of hexapod circular external fixators has simplified the ability to correct complex limb deformities without cumbersome frame reconfigurations. These frames are applied primarily using half pin mountings and may be difficult to utilize given the constraints of traditional half pin constructs. We compared the biomechanical performance of simplified divergent half pin frames to mountings currently being utilized for application of hexapod frames. Three 6-mm half pins per limb segment were placed into sawbones at 60° divergent angles in both the sagittal and coronal planes in a 2-cm diaphyseal fracture gap model. Pin mountings were attached to a standardized four-ring construct. This was compared to similar four-ring frames with two differing pin/wire configurations: (1) two tensioned wires per ring placed at 90° angles, a total eight wires; and (2) two 5-mm half pins per ring placed at 90° angles, a total eight half pins. The divergent 6-mm half pin frames demonstrated similar performance compared the standardized tensioned wire and 5-mm half pin frames in terms of axial micromotion and angular deflection. Based on the mechanical performance of these divergent half pin frames we believe they can be used clinically without detrimental consequences. One or more of the authors (JTW) has received funding from Smith & Nephew.     

One-dimensional measurements of physiological movements of the jugular region using optical coherence tomography

In order to design a semi-automatic laser scalpel for tissue resection in the neck area, it was necessary to examine the biomechanical behavior of these tissues. The aim and scope of this project was to identify if, and to what extent, the tissues shift as a result of respiration and circulation as well as to quantifying not only the amplitude and velocity of these movements but also the modulation. It is important since these movements have to be followed by the laser scalpel. We recorded one-dimensional (1-D) time-related optical coherence tomography (OCT) measurements at defined points on the surface of the neck. The result is the quantification of tissue shifting in the direction of the OCT-line of sight, which means that the z-axis is in direction of the depth, i.e. into the body. The preliminary results of the basic experiments shown here will be used for acquisition and definition of data sets which are necessary to evaluate the technical feasibility of a laser therapy system controlled by OCT, with reference to precision and safety.