Miracle-dz/UniFAR-FTUs huggingface dataset:
Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism

A marquee feature of the powerful human pathogen Mycobacterium tuberculosis is its macrophage parasitism. The intracellular survival of this microorganism rests upon its ability to arrest phagolysosome biogenesis, avoid direct cidal mechanisms in macrophages, and block efficient antigen processing and presentation. Mycobacteria prevent Rab conversion on their phagosomes and elaborate glycolypid and protein trafficking toxins that interfere with Rab effectors and regulation of specific organellar biogenesis in mammalian cells. One of the major Rab effectors affected in this process is the type III phosphatidylinositol 3‐kinase hVPS34 and its enzymatic product phosphatidylinositol 3‐phosphate (PI3P), a regulatory lipid earmarking organellar membranes for specific trafficking events. PI3P is also critical for the process of autophagy, recently recognized as an effector of innate and adaptive immunity. Induction of autophagy by physiological, pharmacological or immunological signals, including the major antituberculosis Th1 cytokine IFN‐γ and its downstream effector p47 GTPase LRG‐47, can overcome mycobacterial phagosome maturation block and inhibit intracellular M. tuberculosis survival. This review summarizes the findings centred around the PI3P‐nexus where the mycobacterial phagosome maturation block and execution stages of autophagy intersect.
Variations in the number of ribosomal DNA units in morphological mutants and normal strains of Candida albicans and in normal strains of Saccharomyces cerevisiae

Naturally occurring strains of Candida albicans are opportunistic pathogens that lack a sexual cycle and that are usually diploids with eight pairs of chromosomes. C. albicans spontaneously gives rise to a high frequency of colonial morphology mutants with altered electrophoretic karyotypes, involving one or more of their chromosomes. However, the most frequent changes involve chromosome VIII, which contains the genes coding for ribosomal DNA (rDNA) units. We have used restriction fragment lengths to analyze the number and physical array of the rDNA units on chromosome VIII in four normal clinical strains and seven morphological mutants derived spontaneously from one of the clinical isolates. HindIII does not cleave the rDNA repeats and liberates the tandem rDNA cluster from each homolog of chromosome VIII as a single fragment, whereas the cleavage at a single site by NotI reveals the size of the single rDNA unit. All clinical strains and morphological mutants differed greatly in the number of rDNA units per cluster and per cell. The four clinical isolates differed additionally among themselves by the size of the single rDNA unit. For a total of 25 chromosome VIII homologs in a total of 11 strains considered, the variability of chromosome VIII was exclusively due to the length of rDNA clusters (or the number of rDNA units) in approximately 92% of the cases, whereas the others involved other rearrangements of chromosome VIII. Only slight variations in the number of rDNA units were observed among 10 random C. albicans subclones and 10 random Saccharomyces cerevisiae subclones grown for a prolonged time at 22 degrees C. However, when grown faster at optimal temperatures of 37 and 30 degrees C, respectively, both fungi accumulated higher numbers of rDNA units, suggesting that this condition is selected for in rapidly growing cells. The morphological mutants, in comparison with the C. albicans subclones, contained a markedly wider distribution of the number of rDNA units, suggesting that a distinct process may be involved in altering the number of rDNA units in these mutants.
Development of atopy and wheezing symptoms in relation to heredity and early pet keeping in a Swedish birth cohort

The role of pet keeping during infancy for the development of allergy and asthma is still controversial. The objective of this population‐based birth cohort study was to assess the development of atopy and different wheezing phenotypes during the first 4 yr of life in relation to heredity and early pet keeping. The cohort comprised all 1228 infants living in a Swedish county who were born over a 1‐yr period. The parents replied to repeated questionnaires and 817 of the children were skin prick tested both at 1 and 4 yr. Cat keeping during the first year of life was associated with an increased risk of a positive skin prick test to cat at 1 yr of age [odds ratio (OR) 2.2, 95% confidence interval (CI) 0.9–5.6], but neither with sensitivity nor clinical symptoms of allergy at 4 yr. Dog keeping during the first year of life was associated with an increased risk of early‐onset transient wheezing, but only in children with parental asthma (adjusted OR 4.3, 95% CI 1.5–12.1). In contrast, early dog keeping had an inverse association with sensitivity to pollen allergen at 4 yr (adjusted OR 0.3, 95% CI 0.1–0.9) and late‐onset wheezing (adjusted OR 0.4, 95% CI 0.2–1.0). Thus, pet keeping during the first year of life was not associated with an increased risk of atopy at 4 yr, although a positive SPT to cat was more common at 1 yr. Our findings may even suggest that dog keeping during the first year of life might provide some protection from pollen allergy and late‐onset wheezing and increase the risk of early‐onset transient wheezing in children with heredity for asthma.
Renal and vascular studies of aqueous extract of Urtica dioica in rats and rabbits

Urtica dioica has a variety of uses in traditional medicine for genitourinary ailments kidney disorders, allergies, diabetes, anemia, gastrointestinal tract ailments, musculoskeletal aches and alopecia. However, only a few of these uses have scientific bases that support their clinical uses. This study was done to evaluate some of the in vivo and in vitro pharmacological actions of this plant. Eighteen local domestic rabbits (Oryctolagus cuniculus) were used for in vitro studies (effect of the plant extract on isolated pulmonary arteries and isolated urinary bladder smooth muscle) and in vivo studies (effect of the extract on renal function). Six male albino rats were used for studying the effects of the plant extract on blood pressure and heart rate. Urtica dioica extract produced a significant increase in urine volume and urinary Na + excretion without significant changes in K
Attenuated Muscle Metaboreflex-Induced Pressor Response during Post-Exercise 1 Muscle Ischemia in Reno-vascular Hypertension 2 3

28 During dynamic exercise, muscle metaboreflex activation (MMA; induced via 29 partial hindlimb ischemia) markedly increases mean arterial pressure (MAP) and MAP is 30 sustained when the ischemia is maintained following the cessation of exercise (post31 exercise muscle ischemia – PEMI). We previously reported that the sustained pressor 32 response during PEMI in normal individuals is driven by a sustained increase in cardiac 33 output (CO) with no peripheral vasoconstriction. However, we have recently shown that 34 the rise in CO with MMA is significantly blunted in hypertension (HTN). The 35 mechanism(s) sustaining the pressor response during PEMI in HTN are unknown. In six 36 chronically instrumented canines, hemodynamic responses were observed during rest, 37 mild exercise (3.2 km/h), MMA and PEMI in the same animals before and after the 38 induction of HTN (Goldblatt 2K1C). In control, MAP, CO and HR increased with MMA 39 (+52 ± 6 mmHg, +2.1 ± 0.3 l/min and +37 ± 7 bpm). After induction of HTN, MAP at rest 40 increased from 97 ± 3 to 130 ± 4 mmHg, and the metaboreflex responses were 41 markedly attenuated (+32 ± 5 mmHg, +0.6 ± 0.2 l/min and +11 ± 3 bpm). During PEMI 42 in HTN, HR and CO were not sustained and MAP fell to normal recovery levels. We 43 conclude that the attenuated metaboreflex-induced HR, CO and MAP responses are not 44 sustained during PEMI in HTN. 45 46 47 48 49 50
Dose titration of intramuscular interferon beta-1a reduces the severity and incidence of flu-like symptoms during treatment initiation

Abstract Background/objective: Flu-like symptoms (FLS) are common side effects of interferon beta (IFNβ) therapy and can negatively affect the willingness of patients with multiple sclerosis to initiate therapy. Although dose titration is commonly used to reduce the severity and incidence of IFNβ-related FLS during treatment initiation, these benefits have not been confirmed in a well controlled study. The objective of this randomized, dose-blinded, parallel-group study was to assess the effect of dose titration on the severity and incidence of FLS during the initial 8 weeks of once-weekly intramuscular (IM) IFNβ-1a administration. Methods: Healthy volunteers were randomized 1:1:1 to one of three IM IFNβ-1a regimens: 3-week titration (weekly quarter-dose increments over 3 weeks to full dose [30 µg]); 6-week titration (biweekly quarter-dose increments over 6 weeks to full dose); or no titration (full dose over 8 weeks). At weekly clinic visits, the severity of each FLS was rated 1 hour pre-injection and 4–6 hours and 12–15 hours post-injection. Study endpoints included post-injection change in FLS severity and post-injection FLS incidence (percentage of subjects with a ≥2-point increase in total FLS severity score) at each time point. Clinical trial registration: Clinicaltrials.gov identifier: NCT01119677. Results: Of 234 subjects enrolled, 194 (83%) completed the study. At 8 weeks, FLS severity was significantly reduced at both post-injection time points with 3-week titration (76% reduction at 4–6 hours, p < 0.001; 37% reduction at 12–15 hours; p < 0.001) and 6-week titration (50% reduction at 4–6 hours, p < 0.001; 32% reduction at 12–15 hours; p = 0.002) compared with no titration. The incidence of FLS was also significantly reduced at both time points with both titration regimens. Safety profiles for both titration regimens were consistent with the current IM IFNβ-1a label. Study limitations included that there is currently no validated assessment tool for evaluating the severity of FLS, that the study enrolled healthy volunteers, that different proportions of females were randomized to the 3-week-titration group than to the 6-week and no-titration groups, and that evaluation of the potential impact of titration on symptoms occurring substantially later after injection was not part of the study protocol. Conclusion: Dose titration during initiation of IM IFNβ-1a reduces FLS severity and incidence in healthy volunteers compared with no titration.
Calcium Channel Blockers and Angiotensin-Converting Enzyme Inhibitors May Be Associated with Altered Atherosclerotic Plaque Size and Morphology

Correlations of atherosclerotic plaque attributes with clinical presentation have not been studied in peripheral arterial disease (PAD). The aim of the current study was to identify clinical variables associated with alterations in PAD plaque morphology. Thirty-one patients underwent intravascular ultrasonography (IVUS) at the time of arteriography for symptomatic PAD. IVUS data were analyzed with radiofrequency techniques for quantification of plaque composition, plaque volume, and total vessel volume. Associations between plaque characteristics and clinical variables were evaluated. Univariable and multivariable analyses were performed using t-test, Pearson correlations, F-tests, and analysis of variance. Calcium (Ca2+) channel blocker use was associated with a smaller total atherosclerotic plaque burden (44.2 ± 2.7 vs 52.9 ± 2.5%; p < .05), and decreased fibrous plaque content (18.2 ± 1.8% vs 24.0 ± 1.9%; p < .05). Angiotensin-converting enzyme (ACE) inhibitor use, however, was associated with a larger total atherosclerotic plaque burden (58.3 ± 2.2% vs 42.9 ± 2.1%; p < .01) and larger fibrous plaque content (27.2 ± 2.0% vs 17.7 ± 1.6%; p < .001). Multivariable analysis was performed to evaluate which factors may differentially impact the response variable measurements of plaque volume to vessel volume. Based on this model, those without the use of an antihyperlipidemic agent or ACE inhibitor had an average total atherosclerotic plaque burden of 47.7%. Those on an antihyperlipidemic agent had an average decrease of 7.0% (p < .05), whereas those on ACE inhibitors had an average increase of 16.2% from the baseline value (p < .001). The use of calcium channel blockers is associated with significantly decreased atherosclerotic plaque burden and decreased fibrous plaque content, whereas the use of ACE inhibitors was associated with an increase in plaque burden and an increased fibrous plaque content. The use of these medications in PAD may alter plaque morphology with the potential to affect clinical outcomes.
Microarray Analysis of Lyn-Deficient B Cells Reveals Germinal Center-Associated Nuclear Protein and Other Genes Associated with the Lymphoid Germinal Center1

Lyn is the only member of the Src family expressed in DT40 B cells, which provide a unique model to study the singular contribution of this protein tyrosine kinase (PTK) family to cell signaling. In these cells, gene ablation of Lyn leads to defective B cell receptor signaling. Complementary DNA array analysis of Lyn-deficient DT40 cells shows that the absence of Lyn leads to down-regulation of numerous genes encoding proteins involved in B cell receptor signaling, proliferation, control of transcription, immunity/inflammation response, and cytoskeletal organization. Most of these expression changes have not been previously associated with Lyn PTK signaling. They include alterations in mRNA levels of germinal center-associated nuclear protein (germinal center-associated DNA primase) (GANP), CD74, CD22, NF-κB, elongation factor 1α, CD79b, octamer binding factor 1, Ig H chain, stathmin, and γ-actin. Changes in GANP expression were also confirmed in Lyn-deficient mice, suggesting that Lyn PTK has a unique function not compensated for by other Src kinases. Because Lyn-deficient mice have impaired development of germinal centers in spleen, the decreased expression of GANP in the Lyn-deficient DT40 cell line and Lyn-deficient mice suggests that Lyn controls the formation and proliferation of germinal centers via GANP. GANP promoter activity was higher in wild-type vs Lyn-deficient cells. Mutation of the PU.1 binding site reduced activity in wild-type cells and had no effect in Lyn-deficient cells. The presence of Lyn enhanced PU.1 expression in a Northern blot. Thus, the following new signaling pathway has been described: Lyn→PU.1→GANP.
[Hearing screening of high risk newborn infants].

OBJECTIVE This prospective study reports on the prevalence of hearing impairment in an at-risk neonatal intensive care unit (NICU) population. DESIGN From 1990 to 1998, 1062 neonates were screened with the use of transitory evoked otoacoustic emissions (TEOAE) and brainstem evoked response audiometry (BERA). RESULTS 934 infants passed the primary screen for both ears, 75 for one ear, adding up to 95%. 17 infants (1.6%) were lost to follow-up. In fourteen infants (1.3%), bilateral hearing impairment above 30 dB was confirmed. While all children with hearing impairment belonged to the group of 862 children receiving aminoglycosides, only one of them presented no other risk factors. In twelve of the hearing impaired children other anamnestic factors, i.e. dysmorphism, prenatal rubella or cytomegaly, family history of hearing loss or severe peri- and postnatal complications seem to be more probable causes of the identified hearing loss. In one of these children, delayed onset or progression of hearing loss is suspected. CONCLUSIONS From our data, aminoglycosides are not an important risk factor for hearing impairment, when serum levels are continuously monitored, as in our cohort. After adjustment for other risk factors, birth weight between 1000 gr and 1500 gr and a gestational age between 29 and 31 weeks were no predictive markers for hearing impairment. It might be speculated that the improved medical treatment in a NICU reduces the probability of hearing impairment for those two groups. Conductive hearing loss as a possible additional cause for hearing impairment was not studied in detail, but the high percentage of malformations detected (four out of fourteen hearing impaired infants) demands further monitoring, close follow-up, adequate treatment and counselling.
Double guidewire technique vs transpancreatic precut sphincterotomy in difficult biliary cannulation.

AIM To compare the outcomes between double-guidewire technique (DGT) and transpancreatic precut sphincterotomy (TPS) in patients with difficult biliary cannulation. METHODS This was a prospective, randomized study conducted in single tertiary referral hospital in Korea. Between January 2005 and September 2010. A total of 71 patients, who bile duct cannulation was not possible and selective pancreatic duct cannulation was achieved, were randomized into DGT (n = 34) and TPS (n = 37) groups. DGT or TPS was done for selective biliary cannulation. We measured the technical success rates of biliary cannulation, median cannulation time, and procedure related complications. RESULTS The distribution of patients after randomization was balanced, and both groups were comparable in baseline characteristics, except the higher percentage of endoscopic nasobiliary drainage in the DGT group (55.9% vs 13.5%, P < 0.001). Successful cannulation rate and mean cannulation times in DGT and TPS groups were 91.2% vs 91.9% and 14.1 ± 13.2 min vs 15.4 ± 17.9 min, P = 0.732, respectively. There was no significant difference between the two groups. The overall incidence of post- endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis was 38.2% vs 10.8%, P < 0.011 in the DGT group and the TPS group; post-procedure pancreatitis was significantly higher in the DGT group. But the overall incidence of post-ERCP hyperamylasemia was no significant difference between the two groups; DGT group vs TPS group: 14.7% vs 16.2%, P < 1.0. CONCLUSION When free bile duct cannulation was difficult and selective pancreatic duct cannulation was achieved, DGT and TPS facilitated biliary cannulation and showed similar success rates. However, post-procedure pancreatitis was significantly higher in the DGT group.
Significance of microvascular density (MVD) in cervical cancer recurrence.

The purpose of this retrospective study of 118 patients with squamous cell cervical cancer from January 1990 to December 1993 was to evaluate angiogenesis as predictive factor of recurrence in cervical cancer stages II-III treated with standard radiotherapy. Microvessel density (MVD) was evaluated and correlated with other prognostic factors. MVD was greater than 20 in 67.8% of patients with recurrence (P = 0.002) in comparison to 39% of patients without. Disease-free survival was shorter in stage IIA and MVD >20 (P = 0.0193) as well as for stage IIB (P < 0.05 ), but not for IIIB (P = 0.1613 ). Global survival was significantly shorter when MVD was >20 (P = 0.0316). For stage IIA and MVD >20 survival was shorter (P = 0.0008) for stage IIB (P < 0.05) but not for IIIB (P = 0.14). Patients younger than 40 years and MVD >20 had poorer disease-free interval and survival (P = 0.0029). MVD in patients with squamous cell cervical cancer stage II and age younger than 40 may play a role in predicting recurrence and survival.
How to use published complete case results from weight loss studies in a missing data sensitivity analysis

In randomized controlled trials of weight loss interventions, high dropout rates are a problem resulting in a large amount of missing outcome data. It is common for participants with missing data to be excluded from analysis (complete‐case analysis). The aim of this article is to demonstrate how published complete‐case results can be used to explore how study results would change depending on assumptions about dropout weight loss.
SPECT image noise power: effects of nonstationary projection noise and attenuation compensation.

The effects of nonstationary projection noise and attenuation compensation are included in a theoretic calculation of the radial noise power spectrum (NPS) of single photon emission computed tomographic (SPECT) images. The nonstationary projection noise is shown to cause a relatively large d.c. component in the NPS, especially for small objects; whereas, attenuation compensation increases the total noise variance while only changing the d.c. component slightly. The theoretic calculation agrees well with a radial NPS estimated from 1,250 SPECT images simulated from projections of random Gaussian noise, even though the effects of discrete data collection and reconstruction were not included in the theoretical model.
Weak State, Strong Community? Promoting Community Participation in Post-Conflict Countries.

Introduction Promoting "community participation" in managing social services is a new orthodoxy among governments and international organizations. It has circumnavigated the globe, appearing in countries as varied as the United States and Malawi, Nicaragua and Bosnia-Herzegovina. It is a buzzword in international development work, edging out the "poverty alleviation" and "human capital" themes that came before it (Botchway, 2000; Cornwall, 2003; Ackerman; 2003). And it has emerged recently in programs that promote international humanitarian assistance for countries or regions at war or in conflict, thus establishing itself in the new relief paradigm. In relief work, the increased role of participation is evident from the mushrooming of parent-teacher associations, parent-school councils, and other varieties of community-based school management organizations. The belief that small civic associations are key ingredients for strengthening civil society and enhancing democracy provides persuasive theoretical support for these interventions. Thus, community participation in educational governance has become part of the formula to achieve both traditional development goals and social reconstruction after a conflict.
Estimated Conductance of G lutamate Receptor Channels Activated during EPSCs at the Cerebellar Mossy F iber-G ranule Cell Synapse

We have analyzed the variance associated with the decay of the non-NMDA receptor component of synaptic currents, recorded from mossy fiber-granule cell synapses in cerebellar slices, to obtain a conductance estimate for the synaptic channel. Current fluctuations arising from the random channel gating properties were separated from those arising from the fluctuations in the population of channels by subtracting the mean excitatory postsynaptic current (EPSC) waveform scaled to the EPSC peak amplitude. A weighted mean single-channel conductance of approximately 20 pS was determined from the relationship between the mean current and the variance around the mean during the decay of evoked and spontaneous synaptic currents. This result suggests that high conductance non-NMDA channels, such as the 1 O-30 pS glutamate receptor channel previously characterized in granule cells, carry the majority of the fast component of the EPSC at this synapse. In addition, otir data are consistent with the activation of surprisingly few (approximately 10) non-NMDA channels by a single packet of transmitter.