Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnosing and managing patients with drug hypersensitivity

ABSTRACT Introduction: Diagnosing and managing drug hypersensitivity is challenging because there are no clear limits between different types of drug reactions. Distinguishing between type A (predictable) and type B (hypersensitivity) reactions when a drug is introduced on the market is not easy. When many people use a drug, adverse reactions can occur, conditioned by diverse genetic profiles, viral infections or concomitant therapy. Occasionally the only tool clinicians have on which to base the diagnosis is the clinical history. Skins tests or in vitro tests sometimes have low sensitivity or are unavailable, and drug provocation tests may be dangerous or strictly forbidden in case of severe cutaneous reactions. Areas covered: This paper reviews the diagnosis and management of the two main types of immunological reactions: IgE-mediated immediate drug hypersensitivity reactions (IDHRs) and non-immediate drug hypersensitivity reactions (NIDHRs). Expert commentary: Although Europe and the United States use different diagnostic methods, patients with history of drug hypersensitivity must avoid the suspicious drug, and clinicians must assess tolerance to safe alternatives under medical surveillance. Sometimes desensitization may be required. There is a consensus about the need to perform genetic testing for specific drugs and give patients proper documentation to prevent future exposure to culprit drugs.
Reliable Lead-Free Rework Process for Stacked CSP Components

Memory module manufacturers face an ongoing challenge to incorporate more functionality and superior performance with each new generation of product offering. The growth in demand for memory capacity is surpassing the pace at which memory component manufacturers are able to cost-effectively produce the next generation of monolithic memory devices. This drives the need for utilizing stacked components for memory module assemblies. The complex nature of stacked chip-scale package (CSP) components coupled with a lead-free process presents unique rework challenges that needed to be studied and addressed. Reworking a CSP is complicated as the solder joints are hidden underneath the component. The process window available for the lead-free rework process is very narrow. There are number of other critical factors, which complicate and affect the repeatability of the rework process. The complications only increase with the use of stacked CSP devices. The rework of package stacked CSP components, which are complex in nature, is a daunting task. The key issues and observations with regard to the issues and challenges associated with the lead-free rework of mirror-imaged package stacked CSP components has been presented in this paper. In addition, the paper also provides a recipe for reliably reworking these packages.
The role of indigenous microflora in the development of murine intestinal fucosyl‐ and sialyltransferases

Most enteric bacteria use intestinal brushborder glycoconjugates as their target host cell receptors. It has been postulated that resident microbes regulate specific glycosyltransferases that are responsible for synthesizing brushborder glycoconjugates. To investigate this hypothesis, we measured glycosyltransferase enzyme activities in intestine from different regions of maturing conventional (CONV), germ‐free (GF), and ex‐germ‐free (XGF) mice and compared them to general enzyme markers of gut development, for example, disaccharidases. High α2,3/6‑Sialyltransferase (ST) activity and low α1,2‐fucosyltransferase (FT) activities were detected from duodenum to colon in suckling CONV mice, but the relative levels of these activities reversed during the third postnatal wk, rapidly reaching adult levels by the fourth wk. These age‐related enzyme changes were significantly attenuated in GF mice, maintaining an immature pattern well past 3 wk. Introduction of gut microflora in GF mice rapidly initiated maturation of glycosyltransferase activity but had no significant affect on developmental programming of dissacharidases. Therefore, in mice, intestinal glycosyltransferase activities are under tissue and developmental control and microflora play a major role in their specific ontogeny but not in overall development. These findings may help explain the regional specificity of commensal bacteria and of enteric pathogens and may also relate age‐related changes in microflora to susceptibility to enteropathogens.
Rye (Secale cereale) supernumerary (B) chromosomes associated with heat tolerance during early stages of male sporogenesis

Background and aims Rye supernumerary (B) chromosomes have an accumulation mechanism involving the B subtelomeric domain highly enriched in D1100- and E3900-related sequences. In this work, the effects of heat stress during the early stages of male meiosis in 0B and +B plants were studied. Methods In-depth cytological analyses of chromatin structure and behaviour were performed on staged rye meiocytes utilizing DAPI, fluorescence in situ hybridization and 5-methylcytosine immune labelling. Quantitative real-time PCR was used to measure heat effects on the expression of the Hsp101 gene as well as the 3·9- and 2·7-kb E3900 forms in various tissues and meiotic stages. Key Results and Conclusions Quantitative real-time PCR established that heat induced equal up-regulation of the Hsp101 gene in 0B and 2B plants, with a marked peak in anthers with meiocytes staged at pachytene. Heat also resulted in significant up-regulation of E3900-related transcripts, especially at pachytene and for the truncated 2·7-kb form of E3900. Cytological heat-induced anomalies in prophase I, measured as the frequency of anomalous meiocytes, were significantly greater in 0B plants. Whereas telomeric sequences were widely distributed in a manner close to normal in the majority of 2B pachytene cells, most 0B meiocytes displayed abnormally clustered telomeres after chromosome pairing had occurred. Relevantly, bioinformatic analysis revealed a significantly high-density heat responsive cis regulatory sequence on E3900, clearly supporting stress-induced response of transcription for the truncated variant. Taken together, these results are the first indication that rye B chromosomes have implications on heat tolerance and may protect meiocytes against heat stress-induced damage.
HIV-1 membrane fusion mechanism: structural studies of the interactions between biologically-active peptides from gp41.

Two synthetic peptides corresponding to sequences in HIV-1LAI gp41, (aa558-595) and T20 (aa 643-678), are strong inhibitors of HIV-1 viral fusion, having EC50 values of 1 microgram/mL and 1 ng/mL, respectively. Previous work suggested that T21 forms a coiled-coil structure in PBS solution, while T20 is primarily nonhelical, and that the inhibitory action of these peptides occurs after the interaction between the viral gp120 protein and the cellular CD4 receptor [Wild, C.T. , Shugars, D. C. , Greenwell, T. K. , McDanal, C. B. , Matthews, T. J. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 9770 and references therein]. The current study uses sedimentation equilibrium (SE), circular dichroism (CD), and viral-fusion assays to quantitatively investigate peptide structure and peptide-peptide interactions. SE analyses of T21 (1-100 microM) indicate that the peptide self associates via a monomer/dimer/tetramer equilibrium; in addition, T20 is monomeric in the range of 1-10 microM and exhibits a complicated monomer/tetramer equilibrium between 20 and 100 microM. Singular value decomposition analyses of the CD spectra of T21 and T20 indicate that the helical content of these peptides in PBS solution is 90% and 20%, respectively. A structural interaction between the two peptides is detected by CD at several concentration ratios of T20:T21. These experiments emphasize that T20 interacts specifically with the tetrameric form of T21. Truncated forms of T20 also exhibit structural interactions with T21 at varying concentration ratios. The ability of T20 and the truncated peptides to interact structurally with tetrameric T21 correlates with antiviral activity. Implications of these findings are discussed in terms of proposed mechanisms of membrane fusion inhibition and the structural changes which occur in gp41 during membrane fusion.
The Cost-Effectiveness of Herpes Simplex Virus-2 Suppressive Therapy With Daily Aciclovir for Delaying HIV Disease Progression Among HIV-1-Infected Women in South Africa

Background: The Partners in Prevention HSV/HIV transmission trial (Partners HSV/HIV Transmission Study) showed that herpes simplex virus-2 (HSV-2) suppressive therapy with daily aciclovir could decrease HIV disease progression amongst HIV-1/HSV-2 coinfected individuals. The cost-effectiveness of daily aciclovir for delaying HIV-1 disease progression in women not eligible for antiretroviral therapy (ART) is estimated. Methods: Resource use/cost data for delivering daily aciclovir at a primary health care HIV clinic were collected in Johannesburg. Effectiveness estimates were obtained from the Partners HSV/HIV Transmission Study trial and epidemiologic data from South Africa. A Markov model simulated the cost-effectiveness of daily aciclovir on HIV-1 disease progression in ART-naive women. Therapy was given to all HIV-1-infected women. Cost-effectiveness was compared against cost per life-year gained (∼US $1200 per LYG) of ART provision in South Africa. Results: For an ART eligibility criteria of CD4 count <200 cells/&mgr;L and the cheapest internationally available aciclovir (US $0.026 per day for 2 × 400 mg aciclovir), the median cost per LYG is US $1023 (95% confidence interval [CI]: 537–2842), whereas it decreases to US $737 (95% CI: 373–2489) if the ART eligibility criteria is CD4 count <350 cells/&mgr;L. Both these projections compare favorably with the estimated cost-effectiveness of ART in South Africa (∼US $1200 per LYG). The cost per LYG increases dramatically for the current aciclovir cost in South Africa (US $0.14 per day), if salary costs are higher and if HSV-2 prevalence amongst HIV-1-infected women are lower. Projections suggest HSV-2 suppressive therapy could dramatically increase the proportion of women initiating ART. Conclusions: HSV-2 suppressive therapy could be an affordable strategy for reducing HIV-1 disease progression and retaining women in care before ART initiation, but cheaply available aciclovir is needed.
Proresolving Actions of Synthetic and Natural Protease Inhibitors Are Mediated by Annexin A1

Annexin A1 (AnxA1) is a glucocorticoid-regulated protein endowed with anti-inflammatory and proresolving properties. Intact AnxA1 is a 37-kDa protein that may be cleaved in vivo at the N-terminal region by neutrophil proteases including elastase and proteinase-3, generating the 33-kDa isoform that is largely inactive. In this study, we investigated the dynamics of AnxA1 expression and the effects of synthetic (sivelestat [SIV]; Eglin) and natural (secretory leukocyte protease inhibitor [SLPI]; Elafin) protease inhibitors on the resolution of LPS-induced inflammation. During the settings of LPS inflammation AnxA1 cleavage associated closely with the peak of neutrophil and elastase expression and activity. SLPI expression increased during resolving phase of the pleurisy. Therapeutic treatment of LPS-challenge mice with recombinant human SLPI or Elafin accelerated resolution, an effect associated with increased numbers of apoptotic neutrophils in the pleural exudates, inhibition of elastase, and modulation of the survival-controlling proteins NF-κB and Mcl-1. Similar effects were observed with SIV, which dose-dependently inhibited neutrophil elastase and shortened resolution intervals. Mechanistically, SIV-induced resolution was caspase-dependent, associated to increased levels of intact AnxA1 and decreased expression of NF-κB and Mcl-1. The proresolving effect of antiproteases was also observed in a model of monosodium urate crystals–induced inflammation. SIV skewed macrophages toward resolving phenotypes and enhanced efferocytosis of apoptotic neutrophils. A neutralizing antiserum against AnxA1 and a nonselective antagonist of AnxA1 receptor abolished the accelerated resolution promoted by SIV. Collectively, these results show that elastase inhibition not only inhibits inflammation but actually promotes resolution, and this response is mediated by protection of endogenous intact AnxA1 with ensuing augmentation of neutrophil apoptosis.
Cutaneous stimulation fails to alter motor unit recruitment in the decerebrate cat.

1. An attempt was made to repeat the observation that cutaneous input to the cat medial gastrocnemius (MG) muscle sometimes had the differential effect of inhibiting motoneurons with slow axonal conduction velocity while simultaneously exciting others with fast conduction velocity. Dual microelectrode recording from intact ventral root filaments was used to study the effects of cutaneous inputs on recruitment order and on firing frequency of physiologically characterized MG motor units in decerebrate cats. Motor responses to pinch of the skin over the lateral surface of the ankle as well as electrical stimulation of the caudal cutaneous sural (CCS) nerve were contrasted with the responses to static muscle stretch as well as muscle vibration. 2. In contrast to the prediction, recruitment order in pairwise tests was the same for skin pinch or CCS stimulation as it was for MG stretch or vibration in all 32 tested pairs of motor units. This sample included seven pairs comprising one slow-twitch (S) and one fast-twitch motor unit, where the predicted reversal of recruitment should have been most apparent. Regardless of the source of excitation, recruitment of motor units of the MG was consistent with Henneman's size principle in approximately 90% of trials. 3. Skin pinch increased the firing rate of 30 of 32 individual motor units previously activated by stretch or vibration, including 7 slow-twitch units. In the remaining two units, skin pinch transiently (100-400 ms) slowed the firing of an S unit in 11 of 13 vibration + pinch trials. The other unit (type unknown) showed one or two retarded spikes in each of four vibration + pinch trials. In three S units, including the lone inhibitable unit and two others that were only excited by skin pinch, there was a significant positive rank correlation between change in unit firing frequency and change in soleus integrated electromyographic activity. (ABSTRACT TRUNCATED AT 400 WORDS)
Isolation of protease-proficient, recombinase-deficient recA mutants of Escherichia coli K-12

We isolated recA mutants with altered protease activity and then examined recombinase activity to determine whether the protease and recombinase functions of the RecA protein of Escherichia coli are separable. We found five mutants that had moderately strong constitutive RecA protease activity but no recombinase activity above the delta recA strain background, the first clear-cut examples of mutants of this class, designated Prtc Rec-. We also isolated 65 mutants that were protease-defective toward the LexA repressor and found that all of them were also recombinase deficient. Four of these mutants retained both partial recombinase activity and partial inducible protease activity. The recombinase-defective mutants were much more sensitive than the recA+ strain to crystal violet, kanamycin, and chloramphenicol, indicating altered membrane permeability. The recA (Prtc Rec-) mutants had a subtle alteration in protease specificity, all being defective in spontaneous induction of phages lambda imm434 and 21. They differed from Prtc Rec+ mutants of comparable or even weaker constitutive protease strength, all of which showed dramatic spontaneous induction of these prophages. However, treating a Prtc Rec- mutant with mitomycin C resulted in significant prophage induction. Thus, the RecA proteins of the Prtc Rec- mutants have constitutive protease activity toward the LexA repressor, but have only DNA damage-activable protease activity toward phage repressors. UV-induced mutagenesis from his to his+ was studied for one Prtc Rec- mutant, and induced mutation frequencies as high as those for the recA+ strain were found despite the absence of recombinase activity.
Calvin Digital Commons Calvin Digital Commons Potassium ion fluxes in corneal epithelial cells exposed to UVB Potassium ion fluxes in corneal epithelial cells exposed to UVB

The goal of this study was to investigate the efflux of K + from human corneal limbal epithelial cells (HCLE) exposed to ambient levels of UVB, which is known to cause apoptosis, and to examine the effect of K + channel blockers on loss of potassium induced by UVB. HCLE cells were exposed to 100–200 mJ/cm 2 UVB, followed by incubation in culture media with 5.5 – 100 mM K + , BDS-1, Ba 2+ or ouabain. To measure intracellular cations, cells were washed in 280 mM sucrose and lysed in DI water. K + and Na + levels in lysates were measured by ion chromatography. HCLE cells showed maximal loss of [K + ] i 10 minutes after exposure to UVB and 5.5 mM K + media, with recovery of normal K + levels after 90 minutes. Treatment with 1 µM BDS-1 following UVB exposure reduced the loss of [K + ] i retained by HCLE cells. Exposure to 0.1–5 mM Ba 2+ inhibited UVB-induced K + loss in a time and dose dependent manner. These results confirm that blocking K + channels in HCLE cells exposed to UVB prevents efflux of K + , confirming that UVB activates K + channels in these cells. Electrophysiology data shows that K + channels remain highly active at least 90 minutes after UVB exposure. HCLE cells exposed to UVB and incubated 0.01–1µM ouabain did not recover from UVB-induced K + loss. These data suggest that the Na/K pump may act to restore [K + ] i to control levels in HCLE cells following UVB exposure and that the pump is not damaged by exposure to UVB. Incubation of HCLE cells exposed to UVB in medium with 25–100mM K + media prevented K + efflux at extracellular concentrations as low as 25mM (the concentration in tear fluid), maintaining control levels of [K + ] i . In all experiments inward fluxes and intracelluar Na+ levels mirrored K + changes, albeit at the expected lower concentrations. The prevention of UVB-induced K +i loss by 25 mM K +o is consistent with the possible contribution of the relatively high K + concentration in tears to protection of the corneal epithelium from ambient UVB.
Change in T2* relaxation time of Hoffa fat pad correlates with histologic change in a rat anterior cruciate ligament transection model

The Hoffa fat pad (infrapatellar fat pad) is a source of post‐traumatic anterior knee pain, and Hoffa disease is a syndrome leading to chronic inflammation of the fat pad. Herein, change in T2* relaxation time of the fat pad was measured in a rodent anterior cruciate ligament transection (ACLX) model in order to (i) examine the causal relationship of anterior cruciate ligament (ACL) deficiency and Hoffa disease and (ii) demonstrate the feasibility of using T2* as an imaging biomarker to monitor disease progression. Three groups of male Sprague Dawley rats (n = 6 each group), received either (i) no intervention; (ii) sham surgery at the right knee; or (iii) right ACLX. T2* relaxation time was measured and histology was examined in the Hoffa fat pad after surgery. At 13 and 18 weeks after surgery, T2* values were significantly higher in the right fat pad than the left (p < 0.001) and significantly higher in the ACLX group than the control and sham groups (p < 0.001). Histology showed fibrosis and degeneration of adipocytes in the right knees of the ACLX group. We conclude that ACL deficiency and Hoffa disease are causally related and that MRI T2* value can serve as an imaging biomarker of Hoffa disease progression. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1348–1355, 2015.
Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis.

PURPOSE Controversy exists as to whether the incidence of graft-versus-host disease (GVHD) is increased after peripheral-blood stem-cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT). We performed a meta-analysis of all trials comparing the incidence of acute and chronic GVHD after PBSCT and BMT reported as of June, 2000. Secondary analyses examined relapse rates after the two procedures. METHODS An extensive MEDLINE search of the literature was undertaken. Primary authors were contacted for clarification and completion of missing information. A review of cited references was also undertaken. Sixteen studies (five randomized controlled trials and 11 cohort studies) were included in this analysis. Data was extracted by two pairs of reviewers and analyzed for the outcomes of interest. Meta-analyses, regression analyses, and assessments of publication bias were performed. RESULTS Using a random effects model, the pooled relative risk (RR) for acute GVHD after PBSCT was 1.16 (95% confidence interval [CI], 1.04 to 1.28; P=.006) when compared with traditional BMT. The pooled RR for chronic GVHD after PBSCT was 1.53 (95% CI, 1.25 to 1.88; P <.001) when compared with BMT. The RR of developing clinically extensive chronic GVHD was 1.66 (95% CI, 1.35 to 2.05; P <.001). The excess risk of chronic GVHD was explained by differences in the T-cell dose delivered with the graft in a meta-regression model that did not reach statistical significance. There was a trend towards a decrease in the rate of relapse after PBSCT (RR = 0.81; 95% CI, 0.62 to 1.05). CONCLUSION Both acute and chronic GVHD are more common after PBSCT than BMT, and this may be associated with lower rates of malignant relapse. The magnitude of the transfused T-cell load may explain the differences in chronic GVHD risk.
Response of lactating dairy cows to degree of steam‐flaked barley grain in low‐forage diets

This study was conducted to investigate the effects of processing method (grinding vs. steam flaking) and increasing densities of steam-flaked barley grain on dry matter intake (DMI), rumen pH and fermentation characteristics, digestibility of dry matter in the total digestive tract (DDTT), and milk production of dairy cows. Eight multiparous mid-lactation Holstein cows averaging 103 ± 24 DIM, 44.5 ± 4.7 kg milk/day and weighing 611 ± 43 kg at the start of the experiment were used in a replicated 4 × 4 Latin square design with 21-day periods. Cows were fed diets consisting of (DM basis) 23.8% corn silage, 13.5% chopped alfalfa hay and 62.7% concentrate. The dietary treatments were either ground barley (GB) using a hammer mill or steam-flaked barley (SFB) - varying density at 390, 340 or 290 g/l. Processing method (GB vs. SFB) did not affect DMI (23.6 kg/day on average), DDTT (71.0% on average), milk yield (43.4 kg/day on average), milk components, rumen pH and molar proportions of acetate, propionate, butyrate and sorting activity. Ruminal isovalerate concentration tended (p = 0.06) to be higher for cows fed GB than those fed SFB-based diets. Decreasing the density of SFB from 390, 340 to 290 g/l tended to linearly increase DMI (p = 0.09), decrease total solids percentage of milk (p = 0.10) and linearly decreased milk urea nitrogen (12.8, 12.4 and 12.1 mg/dl; p = 0.04); also, the sorting index (SI) of the particles retained on the 19.0-mm sieve without affecting the SI of the particles retained on 8.0-mm, 1.18-mm or passed through 1.18-mm sieve (p = 0.05). These results indicated the limited effects of processing method (grinding vs. steam flaking) and densities of SFB (390, 290 or 290 g/l) on cows' performance and feed utilization for dairy cows fed low-forage diets. Therefore, both processing methods could be recommended under current feeding conditions of dairy cows.