Drug resistant typhoid fever (DRT)
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It has been reported that 6-aminomethyl-3-methyl-4H,1,2,4-benzothiadiazine-1, 1-dioxide (AMBD, TAG) is a specific blocker of taurine and beta-alanine responses in the central nervous system. We have re-examined the effect of AMBD on amino acid and synaptically evoked responses recorded from isolated hemisected frog spinal cords by means of the sucrose gap technique. When indirect responses were blocked by adding tetrodotoxin (0.2 microM) or manganese chloride (2 mM) to the normal Ringer solution, AMBD (0.01-0.5 mM) selectively antagonized taurine, beta-alanine, hypotaurine and kojic amine evoked depolarizations of primary afferents at their intramedullary part (dorsal root terminals, DRT) and on dorsal root ganglia (DRG), without significantly affecting responses to glutamate (on DRT), glycine (on DRT) or GABA (on DRT and DRG). Depolarizing responses to taurine and beta-alanine (1 mM) were depressed by up to 50% with 0.1 mM AMBD and often completely antagonized with 0.25 mM AMBD. In normal Ringer solution, AMBD selectively antagonized the dorsal root potential evoked by ventral root stimulation (VR-DRP, threshold at 0.02 mM AMBD, 90% block with 0.25 mM); other synaptic potentials increased in duration and/or amplitude, demonstrating a strong convulsant effect of AMBD. Thus, the depolarizing responses of taurine, beta-alanine and hypotaurine on primary afferents are pharmacologically indistinguishable from the VR-DRP. These results are in agreement with the proposal that taurine or a taurine-like substance (possibly beta-alanine or hypotaurine) is the mediator of VR-DRP in amphibian spinal cord.
Baclofen has been shown to be a selective agonist for a subclass of GABA receptors (GABAB) in many regions of the vertebrate nervous system. On the intraspinal terminals of dorsal roots (DRT), it evokes a pure hyperpolarizing response. We have previously shown that the response of DRT to GABA and some of its analogs (e.g. kojic amine) in isolated frog spinal cord is dual in nature, consisting of a bicuculline-sensitive depolarizing component and a bicuculline-resistant hyperpolarizing component. Under the working hypothesis that the hyperpolarizing component of the GABA-evoked response is mediated by the activation of GABAB receptors, we have examined, using the sucrose gap technique, some characteristics of the response of DRT to baclofen. We have found that this response is stereospecific (L-baclofen being about 100 times more potent than D-baclofen), dependent on [K]o (response amplitude inversely related to [K]o), blocked by barium (0.5 mM causing a reduction of the response amplitude to 37% of control), and is not significantly affected by 4-aminopyridine, nor by inorganic calcium channel blockers (manganese, cobalt, cadmium). Some proposed GABAB antagonists (delta-aminovaleric acid, delta-aminolaevulinic acid, phaclofen) are also rather ineffective at blocking it. These results are therefore consistent with the notion that the baclofen-evoked response of DRT is mediated by an increase in conductance to potassium ions.
The SRT, DRT, and MT of older men (OA) who have experienced a life style of chronic physical activity were compared to those of nonactive men of similar age (ONA), and also to active (YA) and nonactive young men (YNA). Although activity level and age were significant factors, most of the activity level-by-age interaction in all but DRT was attributed to the slower performance of the ONAs. At least in this study, a life style of physical activity appeared to play a more dominant role in determining SRT, DRT, and MT than age. The hypothesis that most of the slowing of responses in the aged is attributable to CNS processing rather than MT decrements is repudiated, since MT results paralleled those of SRT and DRT.
BACKGROUND: Non-specific neck pain (NSNP) is a frequent issue that can negatively affect both mobility and function. Recently, there has been growing interest in newer therapeutic approaches, including rib mobilization and diaphragm release techniques, as potential ways to address NSNP and support better outcomes for those affected. PURPOSE: To find out the immediate effects of how (DRT) combined with (RMT) affects the level of pain and the extent to which patients' functional abilities are improved in cases of NSNP. METHODS: For this prospective RCT, 96 participants aged 20 to 45 years were randomly assigned to one of three equal groups based on their pain score (VAS). Group B engaged in (DRT) for 40 minutes, three times weekly for 8 weeks, in contrast to Group A, which got both RMT combined with DRT. Group C (active control) received advice and some exercises. Measurements were collected before and after the intervention; the primary outcomes included pain severity, evaluated using a visual analog scale (VAS); active neck range of motion (ROM), measured with a cervical range of motion (CROM) device; and neck flexion endurance. Additionally, the secondary outcome of neck-related disability was assessed using the Neck Disability Index (NDI). RESULTS: No statistically significant difference was identified among the three groups at baseline; nevertheless, a treatment effect emerged after 8 weeks (p = 0.001 and f-value = 4.15, ƞ2 = 0.306). A statistically significant time-treatment interaction was seen when comparing the pre- and post-treatment periods in groups A and B (p = 0.001, f-value = 3.16, ƞ2 = 0.251). CONCLUSION: The addition of rib mobilization to diaphragm release techniques in patients with non-specific neck pain resulted in statistically significant improvements in pain intensity, cervical flexion, right lateral rotation, left lateral rotation, right rotation, and neck flexor endurance, with moderate to large effect sizes for pain reduction and cervical motion. However, no statistically significant differences were observed between groups for cervical extension, left rotation, or the Neck Disability Index (NDI), and only a marginal clinical improvement in NDI was noted in Group A. The observed benefits in the combined intervention group may not be attributable solely to rib mobilization. The increased treatment complexity and greater therapist interaction inherent in the combined approach could also have influenced the outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07133646.
The daily rumination time (DRT) and the nycterohemeral pattern of rumination were recorded in six ewes before mating and during late pregnancy and in one unmated ewe. The mean DRT was shorter during pregnancy (mean: 329 min/day) than before mating (mean: 435 min/day). The DRT of the unmated ewe remained constant. The nycterohemeral pattern of rumination changed little during the trial.
The relative importance of different parts of the auditory spectrum to recognition of the Diagnostic Rhyme Test (DRT) and its six speech feature subtests was determined. Three normal hearing subjects were tested twice in each of 70 experimental conditions. The analytical procedures of French and Steinberg [J. Acoust. Soc. Am. 19, 90-119 (1947)] were applied to the data to derive frequency importance functions for each of the DRT subtests and the test as a whole over the frequency range 178-8912 Hz. For the DRT as a whole, the low frequencies were found to be more important than is the case for nonsense syllables. Importance functions for the feature subtests also differed from those for nonsense syllables and from each other as well. These results suggest that test materials loaded with different proportions of particular phonemes have different frequency importance functions. Comparison of the results with those from other studies suggests that importance functions depend to a degree on the available response options as well.
The thermal inactivation characteristics of Bacillus subtilis A spores suspended in skim milk with the use of large-scale ultrahigh temperature (UHT) processing equipment were investigated in terms of survival as measured with two plating media. Data on survival immediately after UHT treatments were recorded in temperature-survivor curves, time-survivor curves, and decimal reduction time (DRT) curves. The temperature-survivor curves emphasized that inactivation is accelerated more by increases in the treatment temperature than by increases in the exposure time. Time-survivor curves and DRT curves were not linear. Generally, exceedingly concave time-survivor curves were observed with the standard plating medium; however, only slightly concave curves were observed when CaCl(2) and sodium dipicolinate were added to the medium. For a given UHT sample, larger D values were obtained by use of the medium with the added CaCl(2) and sodium dipicolinate. The DRT curves of all data were concave and appeared to have two discrete slopes (z(D) values). The z(D) values observed in the upper UHT range (above 260 F; 127 C) were twice those observed at lower test temperatures.
We examined the recovery cycles of auditory event-related potentials (ERPs) in a high-speed auditory discrimination task and in passive conditions. Each trial contained 3 tones cued by a warning flash. In passive conditions, auditory ERPs consisted mainly of N1 (108 msec) and P2 (213 msec) components superimposed on a small CNV. The N1 and P2 were comparable in amplitude and both had prolonged refractory periods. In discriminative reaction time (DRT) conditions the same tones cued or inhibited press responses and elicited additional endogenous components (principally the Nd and P3). ERPs in DRT conditions were superimposed upon a prominent CNV that began after the warning cue and lasted throughout the signal delivery period. The N1 was larger in active than passive conditions and showed less marked refractory effects, while the P2 was smaller and showed more marked refractoriness. Differences between active and passive conditions could be explained by the presence of an endogenous negative potential (the Nd) with a short refractory period that was superimposed upon the N1 and P2. The P3 was recorded only in active conditions. At short ISIs (0.5 sec), P3 amplitudes were reduced and P3 latencies lengthened in parallel with prolongations in reaction time due to so-called psychological refractory period (PRP) effects. Both P3 recovery and the PRP reflected central mechanisms since they were observed at short ISIs when stimuli cueing different responses succeeded one another. N1 and P3 amplitudes diminished over the course of the experiment in both active and passive conditions. The decrease (amounting to about 30% of initial amplitudes) did not appear due to reductions in vigilance, since it was not accompanied by changes in reaction time or response accuracy, or by changes in other endogenous components (CNV or Nd). Short-term N1 habituation was unaffected by long-term amplitude reductions suggesting that independent mechanisms were responsible for the two phenomena.
Operators in an 8 h (n = 18) and a 12 h (n = 16) h shift went through an experiment in which oral temperature, disjunctive reaction time (DRT), tapping, logical reasoning, memory and search tasks were measured at 4 h intervals. A performance curve in DRT and in tapping over a 24 h cycle tended to follow the pattern of the body temperature curve. The curves of mental curves were flattened. The values measured in the two groups of Ss revealed differences of statistical significance.
Young, middle aged, and older subjects were given a Posner-type physical-name matching task, in which stimuli were presented to one or both hemispheres, and a simple discrimination reaction time (DRT) task. Reaction time differed between young and middle aged groups for both tasks with shorter RT for the DRT task. Reaction time for the older group did not differ significantly from that of the middle aged group for either task, although the reaction time for the older group was longer. Reaction time was faster for all age groups when Stimulus 1 and Stimulus 2 were presented to different hemispheres for the matching task than when both stimuli were presented to the same hemisphere. Ipsilateral finger responses (hand relative to hemisphere) were slower than contralateral responses but this was true only with regard to the visual field of presentation for stimulus 2. These data indicate that sharing of information between hemispheres under certain circumstances increases the efficiency of information processing relative to that observed with unilateral visual half-field (hemisphere) presentations and that hand or finger response relative to visual field of presentation is an important factor which must be controlled and examined relative to visual field of presentation.
Decellularized tissues provide biological cues owing to the wealth of structural and regulatory factors that promote angiogenesis, adipogenesis, and myogenesis and facilitate neurite outgrowth. Here, we demonstrated the advantages of decellularized adipose tissue (adipoECM) over defined collagen-based biomaterials for host tissue integration. Three batches of human adipose tissue were decellularized using a rapid decellularization protocol and analyzed using mass spectrometry. To assess the biological activity of the decellularized materials, adipoECM and a reference standard of care biomaterial (Integra®DRT, also containing collagen I and glycosaminoglycans) were implanted subcutaneously, but far from the wound bed (in anatomical potential spaces) of immunocompetent BALB/c mice. The mice were euthanized in the acute (1 day) and chronic (day 60) inflammatory reaction phases, followed by biomaterial excision and Masson’s trichrome immunohistofluorescence imaging of the paraffin-embedded specimens. Each batch of processed tissue passed a quality control check, showing a low level of donor genomic DNA, lack of nuclei, lipids, endotoxins, and bacterial contamination. Mass spectrometry revealed that all batches of decellularized tissue mainly contained collagen I and, to a lesser degree, collagen III, collagen IV, collagen V, laminin, fibrillin, fibronectin, tenascin, and elastin. No acute inflammatory reaction was observed in either material one day post-transplantation. At 60 days post-implantation, different cell types were detected in adipoECM specimens, whereas Integra®DRT remained acellular. Additional immunohistochemical staining of adipoECM revealed CD31-positive cells in the blood vessels. Mesenchymal (CD90 positive) and myeloid (CD14 positive) cells were also detected. Primary cell types involved in soft tissue healing and remodeling were found in the adipoECM-treated group. The ingrowth of blood vessels and mesenchymal cells confirmed the effective integration of adipoECM with host tissues. Our results demonstrate that decellularized adipose tissue implanted away from the wound bed possesses contextual biological activities that promote efficient integration with host tissues.
One-hundred-eleven cases of histopathologically atypical or malignant lipomatous lesions in the somatic soft tissue and retroperitoneum were studied. These consisted of 48 differentiated fatty neoplasms of the somatic soft tissues (DFT-S), 21 fatty neoplasms of the retroperitoneum (DFT-R), 33 myxoid liposarcomas from various sites and nine pleomorphic liposarcomas. DFT-S were defined as lipomatous lesions composed of mature fat and containing atypical stromal cells or lipoblasts. In the somatic soft tissues, this group included lesions that would be classified using published criteria as "atypical lipoma", "pleomorphic lipoma", "well-differentiated lipoma-like liposarcoma", and "sclerosing liposarcoma". All of the DFT-R met previously published criteria for "well differentiated liposarcoma" or "sclerosing liposarcoma". We found no consistent histologic differences between the DFT-S and DRT-R. No pure "round cell" liposarcomas were encountered although many myxoid liposarcomas had "round cell" areas. Follow-up data were available in 80 cases (72%) with a mean follow-up period of over 7 years. Among the DFT-S there were no uncontrollable recurrences, distant metastases, or tumor-related deaths. The depth of the neoplasm correlated with the tendency for local recurrence; no neoplasms primary in the subcutis recurred; 29% of the tumors recurred when they originated in the deep soft tissues or within the muscle. None of the recurrent tumors demonstrated "dedifferentiation." DFT-R had a recurrence rate of 67% and, although there were no distant metastases, nine patients (43%) died of tumor. Five retroperitoneal tumors dedifferentiated but did not metastasize. In light of this experience, we believe that the term "atypical lipoma" is warranted for the DFT-S and "well differentiated liposarcoma" is an appropriate label for the DFT-R. The overall mean survival for the 52 cases of liposarcoma (excluding DFT-S) was 13.6 years. The mean survival in "well differentiated liposarcoma" (11.25 years) was between that for myxoid liposarcoma (16.25 years) and that for pleomorphic liposarcoma (7 years). Six patients (29%) with myxoid liposarcoma developed local recurrences and 6 patients (29%) developed distant metastases and died. Metastasis was always associated with a round cell (or pleomorphic) component with increased numbers of mitotic figures in either the primary tumor or a local recurrence.
Monosyllabic rhyme words were dichotically presented to normal and complete split-brain subjects. In the normal adult population, only one of the words in the dichotic condition was identified. Hence, normal performance was about 50%, with a small but significant right-ear advantage. The split-brain patients yielded the expected marked left deficit, as seen on other dichotic speech tests, and demonstrated a right-ear enhancement, producing a large interear difference. This right-ear enhancement on the dichotic rhyme task (DRT) may suggest a release from central auditory competition in the left hemisphere. The dichotic rhyme task's normative data results and sensitivity to lack of callosal transmission make it worthy of further clinical and basic research.
The recovery of the B-cell population in adult thymectomized, irradiated and bone marrow-reconstituted mice (T X BM mice was estimated at various times after bone marrow transplantation. The spleen cells to be tested were mixed with dexamethasone-resistant thymocytes (DRT) and sheep red blood cells (SRBC) and transferrred to irradiated recipients. The number of plaque-forming cells (PFC) in the spleen of the recipients was determined 7 days later. Using this functional B-cell assay a sequential appearance of the precursors of IgM-, IgG- and IgA-PFC in the spleen of T X BM mice was observed. The precursors of IgM-PFG (IgM-B cells) were present immediately after transplantation. The first IgG-B cells could be detected at 13-16 days after transplantation and the IgA-B cells finally appeared at 22 days after transplantation. The number of B cells reached a constant and normal level at 30 days after transplantation. The IgM-, IgG- and IgA-B cell development in sham-thymectomized, irradiated and bone narrow-reconstituted mice (ST X BM mice) was virtually the same as in T X BM mice.
The totally implantable Novacor left ventricular assist system (LVAS) is currently approaching clinical evaluation. In vivo testing and production are underway with National Institutes of Health (NIH) support. Activity over the past year has focused on manufacturing engineering, preproduction quality assurance, and in vivo experiment completion. Subsequent to successful completion of the NIH-sponsored, 2-year preclinical device readiness test (DRT), a number of refinements were identified and approved by the NIH technical/data review board. Most of these were necessitated by obsolescence or unavailability of electronic components and the decision to use only high reliability military (MIL) qualified electronic components and processes. A few additional refinements were identified to increase design margins, all of which were qualified by accelerated testing. The development of production processes, automated test programs, and MIL compliant environmental stress screening procedures was completed. Production of LVAS subsystems, including core electronic components (hybrids, application-specific integrated circuits, and surface mount boards), was initiated. Animal studies are underway. The clinical trial, at Presbyterian-University Hospital of Pittsburgh and St. Louis University Medical Center, awaits completion of in vivo experiments, protocol development, and Food and Drug Administration approval.
Bacteriophages exert strong selective pressure on soil- and rhizosphere-associated bacteria, including plant-associated symbionts. Reverse transcriptase-associated defense systems of the UG family are widespread across bacterial lineages, yet their ecological roles remain largely undefined. Within this family, UG5 systems are distinguished by reverse transcriptases fused to or associated with a nitrilase domain. Here, we combine phylogenetic, metagenomic, and functional analyses to investigate the evolutionary context and antiviral activity of UG5-associated systems. Phylogenetic analysis of 728 nitrilase domains places UG5-associated nitrilases within a well-supported UG-related radiation encompassing the UG1, UG5, and UG6 families, with UG1 nested within a broader UG5 lineage. Metagenomic analysis further revealed UG5-associated reverse transcriptases in soil- and rhizosphere-derived metagenomes. Based on this observation, we characterized a UG5-large reverse transcriptase (RT)-associated system, here designated DRT11, encoded on the pSymA megaplasmid of Sinorhizobium meliloti RMO17, a nitrogen-fixing symbiont of Medicago sativa. Despite lacking the transmembrane protein typical of canonical UG5-large architectures, DRT11 confers protection against naturally occurring M. sativa rhizosphere phages with podovirus-like morphology. Phage infection assays reveal protection at low multiplicities of infection, consistent with an abortive-infection-like mechanism. Moreover, mutational analyses demonstrate that antiviral activity requires only the RT and its fused C-terminal nitrilase domain, establishing DRT11 as a minimal UG5-associated antiviral system.IMPORTANCEIn this study, we report the functional characterization of a UG5-large reverse transcriptase-associated defense system (DRT11) encoded on the pSymA megaplasmid of the nitrogen-fixing plant symbiont Sinorhizobium meliloti. Using a combination of phylogenetic, metagenomic, genomic, and experimental approaches, we demonstrate that DRT11 functions as a bona fide antiviral defense module, providing protection against naturally occurring rhizosphere phages through a minimal reverse transcriptase-nitrilase architecture. This work establishes direct functional evidence for antiviral activity within the UG5 family and clarifies the evolutionary placement of UG5-associated systems within the broader UG radiation.