Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Galectin-3 in Leukocyte Recruitment in a Murine Model of Lung Infection by Streptococcus pneumoniae1

Pneumonia can be caused by a variety of pathogens, among which Streptococcus pneumoniae causes one of the most common forms of community-acquired pneumonia. Depending on the invading pathogen, the elements of the immune response triggered will vary. For most pathogens, such as Escherichia coli, neutrophil recruitment involves a well-described family of adhesion molecules, β2-integrins. In the case of streptococcal pneumonia, however, neutrophil recruitment occurs mainly through a β2-integrin-independent pathway. Despite decades of research on this issue, the adhesion molecules involved in neutrophil recruitment during lung infection by S. pneumoniae have not been identified. We have previously shown that galectin-3, a soluble mammalian lectin, can be found in lungs infected by S. pneumoniae, but not by E. coli, and can mediate the adhesion of neutrophils on the endothelial cell layer, implying its role in the recruitment of neutrophils to lungs infected with S. pneumoniae. In this study, using galectin-3 null mice, we report further evidence of the involvement of this soluble lectin in the recruitment of neutrophils to S. pneumonia-infected lungs. Indeed, in the absence of galectin-3, lower numbers of leukocytes, mainly neutrophils, were recruited to the infected lungs during infection by S. pneumoniae. In the case of β2-integrin-dependent recruitment induced by lung infection with E. coli, the number of recruited neutrophils was not reduced. Thus, taken together, our data suggest that galectin-3 plays a role as a soluble adhesion molecule in the recruitment of neutrophils to lungs infected by S. pneumoniae, which induces β2-integrin-independent migration.
Cyclic GMP/Cyclic GMP‐Dependent Protein Kinase System Prevents Excitotoxicity in an Immortalized Oligodendroglial Cell Line

Abstract: Previously, we have demonstrated that excitotoxicity of oligodendrocyte‐like cells (OLC), differentiated from immortalized rat O‐2A progenitor cells (CG‐4 cells), is prevented by cyclic AMP‐elevating agents. We now report that some agents that elevate cyclic GMP prevent OLC excitotoxicity. Kainate‐induced injury was prevented by cyclic GMP analogues (8‐bromo‐cyclic GMP and dibutyryl cyclic GMP), a guanylate cyclase activator [atrial natriuretic peptide (ANP)], and phosphodiesterase inhibitors [3‐isobutyl‐1‐methylxanthine (IBMX), ibudilast, propentofylline, and rolipram]. When both forskolin and 8‐bromo‐cyclic GMP were added, kainate‐induced injury was additively prevented. There was a strong positive correlation between suppression of kainate‐induced Ca2+ influx and prevention of injury by these chemicals. The measurement of intracellular cyclic AMP and cyclic GMP by radioimmunoassay demonstrated the following: an increase of cyclic GMP with treatment with 8‐bromo‐cyclic GMP, dibutyryl cyclic GMP, and ANP; an increase of cyclic AMP with treatment with ibudilast and rolipram; and an increase of both cyclic AMP and cyclic GMP with treatment with IBMX and propentofylline. Kainate‐induced Ca2+ influx was decreased by 8‐(4‐chlorophenylthiol)‐guanosine‐3′,5′‐monophosphate, an activator of cyclic GMP‐dependent protein kinase (PKG), or okadaic acid, an inhibitor of protein phosphatases 1 and 2A. RT‐PCR and western blotting of OLC demonstrated transcription of PKG II gene and translation of PKG Iβ mRNA, but no translation of PKG Iα mRNA. Therefore, we concluded that the cyclic GMP/PKG system prevents OLC excitotoxicity.
Child Maltreatment and Educational Attainment in Young Adulthood

There is increasing evidence for the adverse effects of child maltreatment on academic performance; however, most of these studies used selective samples and did not account for potential confounding or mediating factors. We examined the relationship between child physical abuse (PA; severe and non-severe) and sexual abuse (SA) and educational attainment (years of education, failure to graduate from high school) with a Canadian community sample. We used data from the Ontario Child Health Study (N = 1,893), a province-wide longitudinal survey. Potential confounding variables (family socio-demographic and parental capacity) and child-level characteristics were assessed in 1983, and child abuse was determined in 2000-2001 based on retrospective self-report. Results showed that PA and SA were associated with several factors indicative of social disadvantage in childhood. Multilevel regression analyses for years of education revealed a significant estimate for severe PA based on the unadjusted model (−0.60 years, 95% CI = [−0.45, −0.76]); estimates for non-severe PA (0.05 years, CI = [−0.15, 0.26]) and SA (−0.25 years, CI = [−0.09, −0.42]) were not significant. In the adjusted full model, the only association to reach significance was between severe PA and reduced years of education (−0.31 years, CI = [−0.18, −0.44]). Multilevel regression analyses for failure to graduate from high school showed significant unadjusted estimates for severe PA (OR = 1.77, 95% CI = [1.21, 2.58]) and non-severe PA (OR = 1.61, CI = [1.01, 2.57]); SA was not associated with this outcome (OR = 1.40, CI = [0.94, 2.07]). In the adjusted full models, there were no significant associations between child abuse variables and failure to graduate. The magnitude of effect of PA on both outcomes was reduced largely by child individual characteristics. These findings generally support earlier research, indicating the adverse effects of child maltreatment on educational attainment. Of particular note, severe PA was associated with reduced years of education after accounting for a comprehensive set of potential confounding variables and child characteristics.
Foreign-born status as a predictor of engagement in HIV care in a large US metropolitan health system

ABSTRACT We sought to determine the linkage to and retention in HIV care after HIV diagnosis in foreign-born compared with US-born individuals. From a clinical data registry, we identified 619 patients aged ≥18 years with a new HIV diagnosis between 2000 and 2012. Timely linkage to care was the proportion of patients with an ICD-9 code for HIV infection (V08 or 042) associated with a primary care or infectious disease physician within 90 days of the index positive HIV test. Retention in HIV care was the presence of an HIV primary care visit in each 6-month period of the 24-month measurement period from the index HIV test. We used Cox regression analysis with adjustment for hypothesized confounders (age, gender, race/ethnicity, substance abuse, year, and location of HIV diagnosis). Foreign-born individuals comprised 36% (225/619) of the cohort. Index CD4 count was 225/µl (IQR 67–439/µl) in foreign-born compared with 328/µl (IQR 121–527/µl) in US-born individuals (p < .001). The proportion linked to care was 87% (196/225) in foreign-born compared with 77% (302/394) in US-born individuals (p = .002). The adjusted hazard ratio of linkage to HIV care in foreign-born compared with US-born individuals was 1.28 (95% confidence interval [CI], 1.05–1.56). Once linked, there was no difference in retention in care or virologic suppression at 24 months. These results show that despite late presentation to HIV care, foreign-born persons can subsequently engage in HIV care as well as US-born persons. Interventions that promote HIV screening in foreign-born persons are a promising way to improve outcomes in these populations.
CD10 for the distinct differential diagnosis of basal cell carcinoma and benign tumours of cutaneous appendages originating from hair follicle.

AIMS Differential diagnosis between the group of trichoadenoma, trichofolliculoma, trichoepithelioma, trichoblastoma and basal cell carcinoma has been creating some difficulties for the pathologist and the clinicians, particularly in the presence of small specimens. MATERIAL AND METHODS A total of 30 cases of benign tumours of cutaneous appendages originating from the hair follicle and 30 cases of basal cell carcinoma were retrieved from the archives deposited from 2004 to 2008. RESULTS The expression of CD10 in both tumours was graded from [0] to [2+] for each case. The immunoreactivity of CD10 was comparatively examined among the groups and each subgroup. The stromal CD10 immunopositivity of benign tumours of cutaneous appendages originating from the hair follicle was stronger than the other (p = 0.003) regarding both the numerical and the degree of expression. However, peripheral CD10 of basal cell carcinoma was stronger than the other for [1+] immunopositivity (p = 0.03). It was exact opposite for [2+] (p = 0.013). Besides, central CD10 immunopositivity and CD10 reactivity for the subgroups was not significant. CONCLUSIONS CD10 may be very useful for the differential diagnosis between them particularly in the small and superficial biopsies and it may be even a life-saving method in some selected cases.
Clinical implications of ELA2‐, HAX1‐, and G‐CSF‐receptor (CSF3R) mutations in severe congenital neutropenia

Congenital Neutropenia (CN) is a heterogeneous bone marrow failure syndrome characterized by a maturation arrest of myelopoiesis at the level of the promyelocyte/myelocyte stage with peripheral blood absolute neutrophil counts below 0·5 × 109/l. There are two major subtypes of CN as judged by inheritance: an autosomal dominant subtype, e.g. defined by neutrophil elastase mutations (approximately 60% of patients) and an autosomal recessive subtype (approximately 30% of patients), both presenting with the same clinical and morphological phenotype. Different mutations have been described (e.g. HAX1, p14 etc) in autosomal recessive CN, with HAX1 mutations in the majority of these patients. CN in common is considered as a preleukemic syndrome, since the cumulative incidence for leukemia is more than 25% after 20 years of observation. Leukemias occur in both, the autosomal dominant and recessive subtypes of CN. The individual risk for each genetic subtype needs to be further evaluated. Numbers of patients tested for the underlying genetic defect are still limited. Acquired G‐CSFR (CSF3R) mutations are detected in approximately 80% of CN patients who developed acute myeloid leukemia independent of the ELA2 or HAX1 genetic subtype, suggesting that these mutations are involved in leukemogenesis. As the majority of patients benefit from G‐CSF administration, HSCT should be restricted to non‐responders and patients with leukaemic transformation.
Canine Ileal Motor Activity After a Model of Jejunoileal Autotransplantation

ObjectiveTo determine mechanisms by which extrinsic innervation to the jejunoileum controls ileal motility. Summary Background DataSmall bowel transplantation is complicated by diarrhea and delayed gastric emptying, possibly secondary to altered motility. Ileal motility after small bowel transplantation is poorly characterized. MethodsMotor activity was recorded from four dogs during fasting and after feeding small (64 Kcal) or large (256 Kcal) meals. Short-chain fatty acids known to induce unique ileal motor patterns were administered into the distal ileum during fasting. Dogs were studied before and after jejunoileal denervation simulating autotransplantation. ResultsAfter jejunoileal denervation, the ileal migrating motor complex (MMC) persisted but was no longer temporally coordinated with duodenal MMCs. Spontaneous giant migrating contractions occurred more frequently after denervation and more commonly originated proximally in the jejunum, but the velocity of migration did not differ. In contrast, the incidence and characteristics of spontaneous discrete clustered contractions (DCCs) did not differ. Short-chain fatty acids reproducibly initiated giant migrating contractions and discrete clustered contractions in the distal ileum without differences before and after denervation. Large but not small meals inhibited the ileal MMC after denervation. ConclusionsExtrinsic innervation and/or intrinsic neural continuity with the duodenum and/or colon control temporal coordination of ileal motility with the duodenum and modulate postprandial inhibition of fasting motility and presence of giant migrating contractions. These changes in motility patterns may prove important in mediating enteric dysfunction after small bowel transplantation.
Management of bladder function after outpatient surgery.

BACKGROUND This study was designed to test a treatment algorithm for management of bladder function after outpatient general or local anesthesia. METHODS Three hundred twenty-four outpatients, stratified into risk categories for urinary retention, were studied. Patients in category 1 were low-risk patients (n = 227) having non-pelvic surgery and randomly assigned to receive 10 ml/kg or 2 ml/kg of intravenous fluid intraoperatively. They were discharged when otherwise ready, without being required to void. Patients in category 2 (n = 40), also presumed to be low risk, had gynecologic surgery. High-risk patients included 31 patients having hernia or anal surgery (category 3), and 31 patients with a history of retention (category 4). Bladder volumes were monitored by ultrasound in those in categories 2-4, and patients were required to void (or be catheterized) before discharge. The incidence of retention and urinary tract symptoms after surgery were determined for all categories. RESULT Urinary retention affected 0.5% of category 1 patients and none of category 2 patients. Median time to void after discharge was 75 min (interquartile range 120) in category 1 patients (n = 27) discharged without voiding. Fluids administered did not alter incidence of retention or time to void. Retention occurred in 5% of high-risk patients before discharge and recurred in 25% after discharge. CONCLUSION In reliable patients at low risk for retention, voiding before discharge appears unnecessary. In high-risk patients, continued observation until the bladder is emptied is indicated to avoid prolonged overdistention of the bladder.
p50 cdc37 Binds Directly to the Catalytic Domain of Raf as Well as to a Site on hsp90 That Is Topologically Adjacent to the Tetratricopeptide Repeat Binding Site*

Several protein kinases (e.g.pp60 src , v-Raf) exist in heterocomplexes with hsp90 and a 50-kDa protein that is the mammalian homolog of the yeast cell cycle control protein Cdc37. In contrast, unliganded steroid receptors exist in heterocomplexes with hsp90 and a tetratricopeptide repeat (TPR) domain protein, such as an immunophilin. Although p50 cdc37 and TPR domain proteins bind directly to hsp90, p50 cdc37 is not present in native steroid receptor·hsp90 heterocomplexes. To obtain some insight as to how v-Raf selects predominantly hsp90·p50 cdc37 heterocomplexes, rather than hsp90·TPR protein heterocomplexes, we have examined the binding of p50 cdc37 to hsp90 and to Raf. We show that p50 cdc37 exists in separate hsp90 heterocomplexes from the TPR domain proteins and that intact TPR proteins compete for p50 cdc37 binding to hsp90 but a protein fragment containing a TPR domain does not. This suggests that the binding site for p50 cdc37 lies topologically adjacent to the TPR acceptor site on the surface of hsp90. Also, we show that p50 cdc37 binds directly to v-Raf, with the catalytic domain of Raf being sufficient. We propose that the combination of exclusive binding of p50 cdc37 versus a TPR domain protein to hsp90 plus direct binding of p50 cdc37 to Raf allows the protein kinase to select for the dominant hsp90·p50 cdc37 composition that is observed with a variety of protein kinase heterocomplexes immunoadsorbed from cytosols.
Pre- and post-conjugate vaccine epidemiology of pneumococcal serotype 6C invasive disease and carriage within Navajo and White Mountain Apache communities.

BACKGROUND A second-generation 13-valent pneumococcal conjugate vaccine, PCV13, was recently licensed. Although PCV13 includes serotype 6A, the usefulness of that antigen may be limited by the emergence of a new serotype, 6C, which was identified among isolates initially characterized (Quellung reaction) as serotype 6A. The epidemiology of serotype 6C prior to and after 7-valent PCV (PCV7) introduction is incompletely understood. METHODS We analyzed conventionally serotyped 6A (CS6A) pneumococci from invasive disease case patients of all ages and carriage isolates from children and adults obtained in population-based studies among Navajo and White Mountain Apache communities during 1994-2009. Samples were tested by triplex polymerase chain reaction to resolve serotypes 6C and 6A. RESULTS A total of 74 invasive CS6A episodes occurred. All were retyped by polymerase chain reaction; 40 (54.1%) were serotype 6C. The mean annual incidence of serotype 6C invasive disease was 0.3 (95% confidence interval, 0.03-0.9), 0.7 (95% confidence interval, 0.2-1.3), and 1.5 (95% confidence interval, 1.0-2.1) cases per 100,000 population in the years prior to the PCV7 efficacy trial, during the time the PCV7 trial was conducted, and following PCV7 introduction and routine use, respectively (P = .01). In the routine vaccination era, 76% of invasive CS6As were serotype 6C; nearly all cases occurred in adults. The proportion of serotype 6C among CS6A carriage isolates increased from 42% to 61% to 94% in the prevaccine, early vaccine, and routine vaccination eras, respectively. CONCLUSION In the PCV7 routine use era, virtually all serogroup 6 invasive pneumococcal disease and carriage strains among Navajo and White Mountain Apache communities are 6C. Monitoring and evaluation of this and other emerging serotypes among invasive disease and carriage isolates is warranted.
Evolution in caffeoylquinic acid content and histolocalization during Coffea canephora leaf development.

BACKGROUND AND AIMS Caffeoylquinic acids are cinnamate conjugates derived from the phenylpropanoid pathway. They are generally involved in plant responses to biotic and abiotic stress and one of them, chlorogenic acid (5-O-caffeoylquinic acid, 5-CQA), is an intermediate in the lignin biosynthesis pathway. Caffeoylquinic acids, and particularly 5-CQA, are accumulated in coffee beans, where they can form vacuolar complexes with caffeine. Coffea canephora beans are known to have high caffeoylquinic acid content, but little is known about the content and diversity of these compounds in other plant parts. To gain new insights into the caffeoylquinic acid metabolism of C. canephora, caffeoylquinic acid content and in situ localization were assessed in leaves at different growth stages. METHODS HPLC analyses of caffeoylquinic acid content of leaves was conducted in conjunction with detailed histochemical and microspectrofluorometrical analysis. KEY RESULTS AND CONCLUSIONS HPLC analyses revealed that caffeoylquinic acid content was 10-fold lower in adult than in juvenile leaves. The most abundant cinnamate conjugate was 5-CQA, but dicaffeoylquinic acids (particularly in juvenile leaves) and feruloylquinic acids were also present. Using specific reagents, histochemical and microspectrofluorometrical analysis showed that caffeoylquinic acids (mono- and di-esters) were closely associated with chloroplasts in very young leaves. During leaf ageing, they were found to first accumulate intensively in specific chlorenchymatous bundle sheath cells and then in phloem sclerenchyma cells. The association with chloroplasts suggests that caffeoylquinic acids have a protective role against light damage. In older tissues, their presence in the leaf vascular system indicates that they are transported via phloem and confirms their involvement in lignification processes. In accordance with the hypothesis of a complex formation with caffeine, similar tissue distribution was observed for alkaloids and this is further discussed.
Ten-Year Risk of First Recurrent Stroke and Disability After First-Ever Stroke in the Perth Community Stroke Study

Background and Purpose— Limited information exists on the long-term prognosis after first-ever stroke. We aimed to determine the absolute frequency of first recurrent stroke and disability and the relative frequency of recurrent stroke over 10 years after first-ever stroke in Perth, Western Australia. Methods— For a 12-month period beginning February 1989, all individuals with suspected acute stroke or transient ischemic attack who lived in a geographically defined and representative region of Perth were registered prospectively. Patients with a definite first-ever stroke were followed up 10 years after the index event. Results— Over 10 years of follow-up, the cumulative risk of a first recurrent stroke was 43% (95% confidence interval [CI], 34 to 51). After the first year after first-ever stroke, the average annual risk of recurrent stroke was ≈4%. Case fatality at 30 days after first recurrent stroke was 41%, which was significantly greater than the case fatality at 30 days after first-ever stroke (22%) (P =0.003). For 30-day survivors of first-ever stroke, the 10-year cumulative risk of death or new institutionalization was 79% (95% CI, 73 to 85) and of death or new disability was 87% (95% CI, 81 to 92). Conclusions— Over 10 years of follow-up, the risk of first recurrent stroke is 6 times greater than the risk of first-ever stroke in the general population of the same age and sex, almost one half of survivors remain disabled, and one seventh require institutional care. Effective strategies for prevention of stroke need to be implemented early, monitored frequently, and maintained long term after first-ever stroke.
Reconfiguration algorithms for power efficient VLSI subarrays with four-port switches

Techniques to determine subarrays when processing elements of VLSI arrays become faulty have been investigated extensively. These tend to identify the largest subarray that is possible without concentrating on the power efficiency of the resulting subarray. In this paper, we propose new techniques, based on heuristic strategy and dynamic programming, to minimize the interconnect length in an attempt to reduce power dissipation without performance penalty. Our algorithms show that notable improvements in the reduction of the number of long interconnects could be realized in linear time and without sacrificing the size of the subarray. Our evaluations show that, for a VLSI array of size 256/spl times/256, the number of long interconnects in the subarray can be reduced by up to 95 percent for clustered faults and up to 50 percent and 73 percent for a random fault with density of 10 percent and 0.1 percent, respectively, when compared with the most efficient implementation cited in the literature. The interconnect power saving for a VLSI array of size 512/spl times/512 is by up to 11 percent for a random fault. We have also shown that interconnect power savings of up to 14 percent are possible for the cases investigated. Simulations based on several random and clustered fault scenarios clearly reveal the superiority of the proposed techniques for power efficient realizations. In addition, the lower bound of the performance has been proposed to demonstrate that the proposed algorithms are nearly optimal for the cases considered in this paper.