Natural emergence of antigen-reactive T cells in lepromatous leprosy patients during Erythema nodosum leprosum.

Fifteen lepromatous leprosy (LL) patients undergoing erythema nodosum leprosum (ENL) reactions were compared with 13 stable, uncomplicated, anergic individuals of the same leprosy background. ENL patients showed significant antigen-induced leukocyte migration inhibition (migration index = 0.058 ± 0.01), paralleling the values obtained with a responder tuberculoid leprosy population (migration index = 0.04 ± 0.004). Both phytohemagglutinin-induced general T-cell proliferation and, more significantly, antigen-induced lymphoproliferation were enhanced during the acute phase of the reaction. Suppressor cell activity, monitored by a costimulant assay, showed enhanced antigen-stimulated suppression of mitogen responses. Interestingly, the improvement in in vitro T-cell responses was not reflected in dermal reactivity, since 48-h delayed-type hypersensitivity responses after intradermal injection of soluble Mycobacterium leprae antigens continued to be poor. After subsidence of reactional lesions, leukocyte migration inhibition, lymphoproliferation, and suppressor cell activity were reduced to the unresponsive state seen in stable LL patients. Significantly, perturbations of T-cell reactivity are detectable in ENL reactions, indicating the natural but transient emergence of antigen-induced T cells in LL

Assessment of the functional results of hemiarthroplasty in geriatric individuals with unstable intertrochanteric femur fractures

Background: The objective of our study is to measure early weight bearing, mobilization, rapid rehabilitation, complications in unstable intertrochanteric femur after hemiarthroplasty fractures in elderly patients. Methods: Prospective and retrospective, non-randomized study was conducted to assess functional results of hemiarthroplasty in elderly individuals with unstable intertrochanteric femur fractures following surgery in patients who underwent surgery from 2019 to 2021 in department of orthopaedics of Seth Nandlal Dhoot Hospital, Aurangabad. Out of total 44 participants, there were 16 males and 28 females with mean age of 79.54 years of study participants. The patients were evaluated radiologically with routine X-rays i.e. pelvis with both hip joint anteroposterior (AP) view and affected side hip lateral view and clinically early weight bearing, mobilization, rapid rehabilitation and complication with Harris hip score. Results: In our study we observed good result of 86.53±5.73 mean Harris hip score at the end of 1 year was following surgery in 44 study participants who underwent hemiarthroplasty in unstable intertrochanteric femur fractures in elderly patients. Conclusions: Primary hemiarthroplasty offers an essentially pain-free movable joint and is a preferable mode of treatment for older osteoporotic patients who suffers from unstable intertrochanteric femur fractures. Hemiarthroplasty allows for early mobilization and offers rapid stability and mobility, preventing the issues associated with recumbency. Hemiarthroplasty has a lower rate of complications and revision surgery than fixation. According to the Harris hip score, primary bipolar hemiarthroplasty results in a good functional outcome, but long-term monitoring is necessary

Directed transport as a mechanism for protein folding in vivo

We propose a model for protein folding in vivo based on a Brownian-ratchet mechanism in the multidimensional energy landscape space. The device is able to produce directed transport taking advantage of the assumed intrinsic asymmetric properties of the proteins and employing the consumption of energy provided by an external source. Through such a directed transport phenomenon, the polypeptide finds the native state starting from any initial state in the energy landscape with great efficacy and robustness, even in the presence of different type of obstacles. This model solves Levinthal's paradox without requiring biased transition probabilities but at the expense of opening the system to an external field.Comment: 16 pages, 7 figure

Impaired wound healing secondary to bevacizumab

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150555/1/iwj13139_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150555/2/iwj13139.pd

EUS-Guided Needle-Based Confocal Laser Endomicroscopy: A Novel Technique With Emerging Applications

E ndoscopic ultrasound (EUS) has assumed an important role in the evaluation of the gastrointestinal tract in the past few decades. EUS has evolved from a purely diagnostic imaging modality to an interventional procedure that provides a minimally invasive alternative to interventional radiologic and surgical techniques. In EUS, a high-frequency ultrasound transducer is placed into the tip of the endoscope to provide high-quality images of the gastrointestinal tract and nearby structures. 1 Linear echoendoscopes have an advantage over radial instruments in that a fine-needle aspiration (FNA) needle can be guided through the endoscope during real-time EUS monitoring and visualization

Venetoclax induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis

Venetoclax is efficacious in relapsed/refractory t(11;14) multiple myeloma, thus warranting investigation in light-chain amyloidosis (AL). This retrospective cohort includes 43 patients with previously treated AL, from 14 centers in the US and Europe. Thirty-one patients harbored t(11;14), 11 did not, and one t(11;14) status was unknown. Patients received a venetoclax-containing regimen for at least one 21- or 28-day cycle; the median prior treatments was three. The hematologic response rate for all patients was 68%; 63% achieved VGPR/CR. t(11;14) patients had higher hematologic response (81% vs. 40%) and higher VGPR/CR rate (78% vs. 30%, odds ratio: 0.12, 95% CI 0.02-0.62) than non-t(11;14) patients. For the unsegregated cohort, median progression-free survival (PFS) was 31.0 months and median OS was not reached (NR). For t(11;14), median PFS was NR and for non-t(11;14) median PFS was 6.7 months (HR: 0.14, 95% CI 0.04-0.53). Multivariate analysis incorporating age, sex, prior lines of therapy, and disease stage suggested a risk reduction for progression or death in t(11;14) patients. Median OS was NR for either subgroup. The organ response rate was 38%; most responders harbored t(11;14). Grade 3 or higher adverse events occurred in 19% with 7% due to infections. These promising results require confirmation in a randomized clinical trial

Molecular Evolution of a Pervasive Natural Amino-Acid Substitution in Drosophila cryptochrome

Genetic variations in circadian clock genes may serve as molecular adaptations, allowing populations to adapt to local environments. Here, we carried out a survey of genetic variation in Drosophila cryptochrome (cry), the fly’s dedicated circadian photoreceptor. An initial screen of 10 European cry alleles revealed substantial variation, including seven non-synonymous changes. The SNP frequency spectra and the excessive linkage disequilibrium in this locus suggested that this variation is maintained by natural selection. We focused on a non-conservative SNP involving a leucine - histidine replacement (L232H) and found that this polymorphism is common, with both alleles at intermediate frequencies across 27 populations surveyed in Europe, irrespective of latitude. Remarkably, we were able to reproduce this natural observation in the laboratory using replicate population cages where the minor allele frequency was initially set to 10%. Within 20 generations, the two allelic variants converged to approximately equal frequencies. Further experiments using congenic strains, showed that this SNP has a phenotypic impact, with variants showing significantly different eclosion profiles. At the long term, these phase differences in eclosion may contribute to genetic differentiation among individuals, and shape the evolution of wild populations

The Role of Millimeter-Waves in the Distance Measurement Accuracy of an FMCW Radar Sensor

High-accuracy, short-range distance measurement is required in a variety of industrial applications e.g., positioning of robots in a fully automated production process, level measurement of liquids in small containers. An FMCW radar sensor is suitable for this purpose, since many of these applications involve harsh environments. Due to the progress in the field of semiconductor technology, FMCW radar sensors operating in different millimeter-wave frequency bands are available today. An important question in this context, which has not been investigated so far is how does a millimeter-wave frequency band influence the sensor accuracy, when thousands of distance measurements are performed with a sensor. This topic has been dealt with for the first time in this paper. The method used for analyzing the FMCW radar signal combines a frequency- and phase-estimation algorithm. The frequency-estimation algorithm based on the fast Fourier transform and the chirp-z transform provides a coarse estimate of the target distance. Subsequently, the phase-estimation algorithm based on a cross-correlation function provides a fine estimate of the target distance. The novel aspects of this paper are as follows. First, the estimation theory concept of Cramér-Rao lower bound (CRLB) has been used to compare the accuracy of two millimeter-wave FMCW radars operating at 60 GHz and 122 GHz. In this comparison, the measurement parameters (e.g., bandwidth, signal-to-noise ratio) as well as the signal-processing algorithm used for both the radars are the same, thus ensuring an unbiased comparison of the FMCW radars, solely based on the choice of millimeter-wave frequency band. Second, the improvement in distance measurement accuracy obtained after each step of the combined frequency- and phase-estimation algorithm has been experimentally demonstrated for both the radars. A total of 5100 short-range distance measurements are made using the 60 GHz and 122 GHz FMCW radar. The measurement results are analyzed at various stages of the frequency- and phase-estimation algorithm and the measurement error is calculated using a nanometer-precision linear motor. At every stage, the mean error values measured with the 60 GHz and 122 GHz FMCW radars are compared. The final accuracy achieved using both radars is of the order of a few micrometers. The measured standard deviation values of the 60 GHz and 122 GHz FMCW radar have been compared against the CRLB. As predicted by the CRLB, this paper experimentally validates for the first time that the 122 GHz FMCW radar provides a higher repeatability of micrometer-accuracy distance measurements than the 60 GHz FMCW radar. View Full-Tex