Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and Protective Efficacy of Intramuscular Vaccination with a Live aroA Derivative of Pasteurella multocida B:2 against Experimental Hemorrhagic Septicemia in Calves

ABSTRACT Three groups of five calves, namely, V1, V2, and V3, were immunized intramuscularly at 4 and 8 weeks of age with ca. 109, 108, and 107 CFU, respectively, of a derivative of Pasteurella multocida B:2 wild-type strain 85020 containing a deletion in the aroA gene (strain JRMT12). The first and second vaccinations resulted in significantly (P < 0.01) higher rectal temperature responses in groups V1 and V2 than in group V3. Serum immunoglobulin M (IgM) and IgG titers did not increase in any group until after the second vaccination and were then significantly higher in groups V1 and V2 than in group V3 (P = 0.001 for both IgM and IgG). All vaccinated groups and three unvaccinated challenge control calves (group CC) were injected subcutaneously at 10 weeks of age with ca. 107 CFU of strain 85020. Vaccinated calves survived the challenge, but two CC animals developed clinical disease and were killed for humane reasons. After challenge, mean serum amyloid A concentrations were significantly higher (P < 0.001) in the CC group than in the vaccinated groups. Postmortem examination revealed that calves in the CC group showed the most extensive range of bacteriologically positive tissues and gross and histopathological lesions. Overall, a clear dose-dependent response was present, with those receiving a higher vaccine dose being less affected clinically, bacteriologically, and pathologically by the wild-type challenge. The V2 treatment appeared to give the best combination of high immune response, protection, and safety.
Comparing Applanation Tonometry and Rebound Tonometry in Glaucomatous and Ocular Hypertensive Eyes

Purpose TO describe Goldmann applanation tonometer (GAT) and rebound tonometer (RT) agreement in measuring intraocular pressure (IOP) in glaucomatous and ocular hypertensive (OH) eyes and to evaluate central corneal thickness (CCT) influence on RT readings. Methods A total of 347 eyes were enrolled and IOP measured between 9 and 11 am. Rebound tonometry was performed first (RT1), followed by 3 consecutive GAT measurements and by a second RT reading (RT2), within a 5-minute span. Mean IOP (±SD) values were compared by means of paired t-test. Agreement between GAT and RT1 (test 1) and RT2 (test 2) was evaluated with Bland-Altman method, whereas a linear function described the relationship between CCT and IOP taken with RT. Results Mean IOP (±SD) taken with RT1, GAT, and RT2 was 18.1±4.3, 15.6±3.3, and 16.3±3.9 mmHg, respectively. Readings were within ±3 mmHg in 63.7% and 86.7% of eyes for test 1 and 2, respectively. A significant (p<0.001) proportional bias was noted on both tests (95% limits of agreement: −2.3/7.4 and −3.6/5.0 mmHg for test 1 and 2, respectively). Agreement between instruments decreased for increasing IOP. Rebound tonometry readings increased by 4.6 and 4.1 mmHg for RT1 and RT2, respectively, for each 100–μm CCT increase. Conclusions When used first, RT significantly overestimated IOP compared with GAT. Differences became clinically negligible when RT was used immediately after GAT. Repeated applanation tonometry may explain this observation. Agreement between instruments was acceptable for low IOP, but worsened with increasing IOP values. RT is significantly influenced by CCT. Goldmann applanation tonometer and RT should not be used interchangeably.
Can images of pain enhance patient–clinician rapport in pain consultations?

A variety of treatment outcomes in chronic pain are influenced by patient–clinician rapport. Patients often report finding it difficult to explain their pain, and this potential obstacle to mutual understanding may impede patient–clinician rapport. Previous research has argued that the communication of both patients and clinicians is facilitated by the use of pain-related images in pain assessments. This study investigated whether introducing pain-related images into pain assessments would strengthen various components of patient–clinician rapport, including relative levels of affiliation and dominance, and interpersonal coordination between patient and clinician behaviour. Videos of 35 pain assessments in which pain images were present or absent were used to code behavioural displays of patient and clinician rapport at fixed intervals across the course of the assessment. Mixed modelling was used to examine patterns of patient and clinician affiliation and dominance with consultation type (Image vs Control) as a moderator. When pain images were present, clinicians showed more affiliation behaviour over the course of the consultation and there was greater correspondence between the affiliation behaviour of patient and clinician. However, relative levels of patient and clinician dominance were unaffected by the presence of pain images in consultations. Additional analyses revealed that clinicians responded directly to patients’ use of pain images with displays of affiliation. Based on the results of this study, we recommend further investigation into the utility and feasibility of incorporating pain images into pain assessments to enhance patient–clinician communication.
Interspecies recombination, and phylogenetic distortions, within the glutamine synthetase and shikimate dehydrogenase genes of Neisseria meningitidis and commensal Neisseria species

Visual inspection showed clear evidence of a history of intraspecies recombinational exchanges within the neighbouring meningococcal shikimate dehydrogenase (aroE ) and glutamine synthetase (glnA) genes, which was supported by the non‐congruence of the trees constructed from the sequences of these genes from different meningococcal strains, and by statistical tests for mosaic structure. Many examples were also found of highly localized interspecies recombinational exchanges between the meningococcal aroE and glnA genes and those of commensal Neisseria species. These exchanges appear to have inflated the sequence variation at these loci, and have resulted in major distortions of the phylogenetic trees constructed from the sequences of the aroE and glnA genes of human pathogenic and commensal Neisseria species. Statistical tests for sequence mosaicism, and for anomalies within the Neisseria species trees, strongly supported the view that frequent interspecies recombination has occurred within aroE and glnA. The high levels of sequence variation, and intra‐ and interspecies recombination, within aroE and glnA did not appear to be due to a ‘hitch‐hiking’ effect caused by positive selection for variation at a neighbouring gene. Our results suggest that interspecies recombinational exchanges with commensal Neisseria occur frequently in some meningococcal ‘housekeeping’ genes as they can be observed readily even when there appears to be no obvious selection for the recombinant phenotypes.
1-V Low-Power Programmable Rail-to-Rail Operational Amplifier With Improved Transconductance Feedback Technique

A low-power process-independent programmable transconductance rail-to-rail operational amplifier (OpAmp) is proposed. It employs an improved transconductance feedback loop that senses the transconductance (gmT) accurately and enforces it to be equal to the conductance of a reference resistor. Experimental results in a 0.13- μm standard CMOS technology under a 1-V power supply demonstrate a continuous programmable gmT range from 87 to 165 μA/V with minimum fluctuation of ±2.4% and programmable deviation less than 4.5% from the reference value. The OpAmp achieves a unity-gain bandwidth of 3.7 MHz with a 95-pF load while only consuming 187 μA of quiescent current. The figure of merit of the proposed OpAmp is 1879 MHz·pF/mA.
Preventing Hearing Damage Using Topical Dexamethasone During Reversible Cochlear Ischemia: An Animal Model

Hypothesis: Local application of dexamethasone to the round window (RW) niche prevents cochlear damage caused by local reversible ischemia. Background: Cochlear ischemia induced by internal auditory artery (IAA) compression/stretching is thought to cause postoperative sensory hearing loss after attempted hearing preservation removal of acoustic neuroma tumors. Dexamethasone administered to the RW niche traveling through the membrane to the cochlear fluids may prevent ischemic damage. Materials and Methods: Ten young albino rabbits were used for this study. Ischemic episodes were induced by compressing the IAA. Laser Doppler cochlear blood flow was measured using a probe positioned at the RW niche. Transtympanic electrocochleography was measured at 4, 8, and 12 kHz. In 5 test ears, dexamethasone was administered topically at the RW for approximately 50 minutes before the IAA compressions, whereas in 5 control ears, saline was applied in the same way. Each ear underwent one 10-minute IAA compression with a 60-minute postischemic period of transtympanic electrocochleography monitoring. Results: In both control- and dexamethasone-treated ears, ischemic episodes measured by Laser Doppler cochlear blood flow were comparable. Fifty minutes after IAA decompression, in dexamethasone-pretreated ears, cochlear microphonic and compound action potential amplitudes at all test frequencies were 10 to 15% less reduced than those in control ears. Compound action potential latencies in dexamethasone-pretreated ears resulted in shorter latency delay than in control ears. Conclusion: The RW seems to be an efficacious route for the administration of dexamethasone into the inner ear. Dexamethasone showed a protective effect on cochlear function after local ischemia. Transtympanic electrocochleography was found to be a sufficient and effective tool in monitoring hearing.
MELD Exceptions and Rates of Waiting List Outcomes

Model for End‐stage Liver Disease (MELD)‐based allocation of deceased donor livers allows exceptions for patients whose score may not reflect their true mortality risk. We hypothesized that organ procurement organizations (OPOs) may differ in exception practices, use of exceptions may be increasing over time, and exception patients may be advantaged relative to other patients. We analyzed longitudinal MELD score, exception and outcome in 88 981 adult liver candidates as reported to the United Network for Organ Sharing from 2002 to 2010. Proportion of patients receiving an HCC exception was 0–21.4% at the OPO‐level and 11.9–18.8% at the region level; proportion receiving an exception for other conditions was 0.0%–13.1% (OPO‐level) and 3.7–9.5 (region‐level). Hepatocellular carcinoma (HCC) exceptions rose over time (10.5% in 2002 vs. 15.5% in 2008, HR = 1.09 per year, p<0.001) as did other exceptions (7.0% in 2002 vs. 13.5% in 2008, HR = 1.11, p<0.001). In the most recent era of HCC point assignment (since April 2005), both HCC and other exceptions were associated with decreased risk of waitlist mortality compared to nonexception patients with equivalent listing priority (multinomial logistic regression odds ratio [OR] = 0.47 for HCC, OR = 0.43 for other, p<0.001) and increased odds of transplant (OR = 1.65 for HCC, OR = 1.33 for other, p<0.001). Policy advantages patients with MELD exceptions; differing rates of exceptions by OPO may create, or reflect, geographic inequity.
Imidapril inhibits cerebral aneurysm formation in an angiotensin-converting enzyme-independent and matrix metalloproteinase-9-dependent manner.

BACKGROUND Cerebral aneurysms (CAs) have a high prevalence in the general population and cause lethal subarachnoid hemorrhage. We recently demonstrated that chronic inflammation is an underlying pathogenesis of CA. However, we identified the negative involvement of angiotensin receptor signaling in the pathogenesis of CA. OBJECTIVE To elucidate the involvement of the renin-angiotensin system (RAS) by assessing the expression and activity of angiotensin-converting enzyme (ACE), a key enzyme of RAS, during CA formation and evaluating the effect of imidapril, an ACE inhibitor and a potent inhibitor of matrix metalloproteinase-9 (MMP-9), on CA formation. METHODS Surgically induced CA models of rats were used. Imidapril was given intraperitoneally to rats, and aneurysm size and medial thickness of CAs were examined 1 month after induction. Then, ACE and MMP-9 expression was assessed by immunostaining and Western blot analysis. The MMP-9 activity was evaluated by gelatin zymography, and ACE expression in human CA walls was assessed by immunostaining. RESULTS Imidapril significantly suppressed the size and medial thinning of induced CAs. The expression and activity of ACE were not induced in CA walls. Furthermore, imidapril treatment did not influence ACE expression and activity, suggesting that the inhibitory effect of imidapril was independent of an inhibition of the RAS. Imidapril inhibited MMP-9 activity upregulated in CA walls. In an in vitro study, imidapril suppressed MMP-9 activity in a dose-dependent manner. In human CA walls, as in the rat model, ACE expression was not upregulated. CONCLUSION Angiotensin-converting enzyme is not involved in the pathogenesis of CA formation. Imidapril suppresses CA formation in an ACE-independent and MMP-9-dependent manner.
Identification of Helicobacter pylori and OtherHelicobacter Species by PCR, Hybridization, and Partial DNA Sequencing in Human Liver Samples from Patients with Primary Sclerosing Cholangitis or Primary Biliary Cirrhosis

ABSTRACT Helicobacter pylori was identified in human liver tissue by PCR, hybridization, and partial DNA sequencing. Liver biopsies were obtained from patients with primary sclerosing cholangitis (n = 12), primary biliary cirrhosis (n = 12), and noncholestatic liver cirrhosis (n = 13) and (as controls) normal livers (n = 10). PCR analyses were carried out using primers for the Helicobacter genus, Helicobacter pylori(the gene encoding a species-specific 26-kDa protein and the 16S rRNA),Helicobacter bilis, Helicobacter pullorum, andHelicobacter hepaticus. Samples from patients with primary biliary cirrhosis and primary sclerosing cholangitis (11 and 9 samples, respectively) were positive by PCR with Helicobactergenus-specific primers. Of these 20 samples, 8 were positive with the 16S rRNA primer and 9 were positive with the 26-kDa protein primer ofH. pylori. These nine latter samples were also positive by Southern blot hybridization for the amplified 26-kDa fragment, and four of those were verified to be H. pylori by partial 16S rDNA sequencing. None of the samples reacted with primers for H. bilis, H. pullorum, or H. hepaticus. None of the normal livers had positive results in theHelicobacter genus PCR assay, and only one patient in the noncholestatic liver cirrhosis group, a young boy who at reexamination showed histological features suggesting primary sclerosing cholangitis, had a positive result in the same assay. Helicobacterpositivity was thus significantly more common in patients with cholestatic diseases (20 of 24) than in patients with noncholestatic diseases and normal controls (1 of 23) (P = <0.00001). Patients positive for Helicobacter genus had significantly higher values of alkaline phosphatases and prothrombin complex than Helicobacter-negative patients (P = 0.0001 and P = 0.0003, respectively). Among primary sclerosing cholangitis patients,Helicobacter genus PCR positivity was weakly associated with ulcerative colitis (P = 0.05). Significant differences related to blood group or HLA status were not found.
Inclusion of Gaming Disorder in ICD has more advantages than disadvantages

This paper is a response to a recent debate paper in which Aarseth et al. argue that the inclusion of a formal diagnosis and categories for problematic video gaming or Gaming Disorder (GD) in the World Health Organization’s 11th Revision of the International Classification of Diseases (ICD-11) is premature and therefore the proposal should be removed. The present authors systematically address all the six main arguments presented by Aarseth et al. and argue that, even though some of the concerns presented in the debate paper are legitimate, the inclusion of GD in ICD-11 has more advantages than disadvantages. Furthermore, the present authors also argue that the two GD subtypes (“GD, predominantly online” and “GD, predominantly offline”) are unnecessary and rather problematic; the main category for GD would be perfectly sufficient.
Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring.

OBJECT The early pathophysiological features of traumatic brain injury observed in the intensive care unit (ICU) have been described in terms of altered cerebral blood flow, altered brain metabolism, and neurochemical excitotoxicity. Seizures occur in animal models of brain injury and in human brain injury. Previous studies of posttraumatic seizures in humans have been based principally on clinical observations without a systematic approach to electroencephalographic (EEG) recording of seizures. The purpose of this study was to determine prospectively the incidence of convulsive and nonconvulsive seizures by using continuous EEG monitoring in patients in the ICU during the initial 14 days post-injury. METHODS Ninety-four patients with moderate-to-severe brain injuries underwent continuous EEG monitoring begin-ning at admission to the ICU (mean delay 9.6+/-5.4 hours) and extending up to 14 days postinjury. Convulsive and nonconvulsive seizures occurred in 21 (22%) of the 94 patients, with six of them displaying status epilepticus. In more than half of the patients (52%) the seizures were nonconvulsive and were diagnosed on the basis of EEG studies alone. All six patients with status epilepticus died, compared with a mortality rate of 24% (18 of 73) in the nonseizure group (p<0.001). The patients with status epilepticus had a shorter mean length of stay (9.14+/-5.9 days compared with 14+/-9 days [t-test, p<0.031). Seizures occurred despite initiation of prophylactic phenytoin on admission to the emergency room, with maintenance at mean levels of 16.6+/-2.8 mg/dl. No differences in key prognostic factors (such as the Glasgow Coma Scale score, early hypoxemia, early hypotension, or 1-month Glasgow Outcome Scale score) were found between the patients with seizures and those without. CONCLUSIONS Seizures occur in more than one in five patients during the 1st week after moderate-to-severe brain injury and may play a role in the pathobiological conditions associated with brain injury.
Adaptation of the Lumbar Spine to Different Positions in Bicycle Racing

Study Design. A radiologic and electromyographic study was done of the adaptation of the lumbar spine to high‐performance cycling. Objectives. To evaluate changes in the lumbar spine produced by different cycling positions on different types of bicycles used during competition. Methods. Three professional cyclists were observed to evaluate changes in the lumbar spine. Radiographs were obtained of the different positions adopted by the cyclists during competition, and changes in the angles of the lumbar spine were measured. An electromyographic study was done of the abdominal, lumbar, and thoracic paravertebral muscles. Results. The cyclists' positions involved a change from discal lordosis to kyphosis. To obtain a more aerodynamic position, the cyclists flexed the hip and made the pelvis horizontal without changing disc angles. The contraction of paravertebral lumbar muscles was proportional to pedalling intensity and decreased in more aerodynamic positions. The tone of the paravertebral thoracic muscles depended on the extent of cervical hyperextension. Abdominal muscles remained relaxed in all bicycle positions and with all pedalling intensities. Conclusions. The changes observed could modify the normal biomechanics of the lumbar spine, but the overall mechanical load on the spine is reduced by shifting weight onto the upper limbs. The imbalance that occurs between the activity of flexor and extensor muscles could cause lumbar pain in persons without proper physical preparation.
Efficient methylation of C2 in l-tryptophan by the cobalamin-dependent radical S-adenosylmethionine methylase TsrM requires an unmodified N1 amine

TsrM catalyzes the methylation of C2 in l-tryptophan (Trp). This reaction is the first step in the biosynthesis of the quinaldic acid moiety of the thiopeptide antibiotic thiostrepton, which exhibits potent activity against Gram-positive pathogens. TsrM is a member of the radical S-adenosylmethionine (SAM) superfamily of enzymes, but it does not catalyze the formation of 5′-deoxyadenosin-5′-yl or any other SAM-derived radical. In addition to a [4Fe–4S] cluster, TsrM contains a cobalamin cofactor that serves as an intermediate methyl carrier in its reaction. However, how this cofactor donates a methyl moiety to the Trp substrate is unknown. Here, we showed that the unmodified N1 position of Trp is important for turnover and that 1-thia-Trp and 1-oxa-Trp serve as competitive inhibitors. We also showed that β-cyclopropyl-Trp undergoes C2 methylation in the absence of cyclopropyl ring opening, disfavoring mechanisms that involve unpaired electron density at C3 of the indole ring. Moreover, we showed that all other indole-substituted analogs of Trp undergo methylation at varying but measurable rates and that the analog 7-aza-Trp, which is expected to temper the nucleophilicity of C2 in Trp, is a very poor substrate. Last, no formation of cob(II)alamin or substrate radicals was observed during the reaction with Trp or any molecule within a tested panel of Trp analogs. In summary, our results are most consistent with a mechanism that involves two polar nucleophilic displacements, the second of which requires deprotonation of the indole nitrogen in Trp during its attack on methylcobalamin.
Breaking self‐tolerance during autoimmunity and cancer immunity: Myeloid cells and type I IFN response regulation

The generation and regulation of innate immune signals are key determinants of autoimmune pathogenesis. Emerging evidence suggests that parallel processes operating in the setting of solid tumors can similarly determine the balance between tolerance and immunity and ultimately the effectiveness of the antitumor immune response. In both contexts, self‐specific responses start with innate immune cell activation that leads to the initial break in self‐tolerance, which can be followed by immune response amplification and maturation through innate‐adaptive crosstalk, and finally immune‐mediated tissue/tumor destruction that can further potentiate inflammation. Of particular importance for these processes is type I IFN, which is induced in response to endogenous ligands, such as self‐nucleic acids, and acts on myeloid cells to promote the expansion of autoreactive or tumor‐specific T cells and their influx into the target tissue. Evidence from the study of human disease pathophysiology and genetics and mouse models of disease has revealed an extensive and complex network of negative regulatory pathways that has evolved to restrain type I IFN production and activity. Here, we review the overlapping features of self‐ and tumor‐specific immune responses, including the central role that regulators of the type I IFN response and innate immune cell activation play in maintaining tolerance, and discuss how a better understanding of the pathophysiology of autoimmunity can help to identify new approaches to promote immune‐mediated tumor destruction.