Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Short-Chain Fatty Acids, Produced by Anaerobic Bacteria, in the Cystic Fibrosis Airway.

RATIONALE Anaerobic bacteria are present in large numbers in the airways of people with cystic fibrosis (PWCF). In the gut, anaerobes produce short-chain fatty acids (SCFAs) that modulate immune and inflammatory processes. OBJECTIVES To investigate the capacity of anaerobes to contribute to cystic fibrosis (CF) airway pathogenesis via SCFAs. METHODS Samples of 109 PWCF were processed using anaerobic microbiological culture with bacteria present identified by 16S RNA sequencing. SCFA levels in anaerobic supernatants and bronchoalveolar lavage (BAL) were determined by gas chromatography. The mRNA and/or protein expression of two SCFA receptors, GPR41 and GPR43, in CF and non-CF bronchial brushings and 16HBE14o(-) and CFBE41o(-) cells were evaluated using reverse transcription polymerase chain reaction, Western blot analysis, laser scanning cytometry, and confocal microscopy. SCFA-induced IL-8 secretion was monitored by ELISA. MEASUREMENTS AND MAIN RESULTS Fifty-seven (52.3%) of 109 PWCF were anaerobe positive. Prevalence increased with age, from 33.3% to 57.7% in PWCF younger (n = 24) and older (n = 85) than 6 years of age. All evaluated anaerobes produced millimolar concentrations of SCFAs, including acetic, propionic, and butyric acids. SCFA levels were higher in BAL samples of adults than in those of children. GPR41 levels were elevated in CFBE41o(-) versus 16HBE14o(-) cells; CF versus non-CF bronchial brushings; and 16HBE14o(-) cells after treatment with cystic fibrosis transmembrane conductance regulator inhibitor CFTR(inh)-172, CF BAL, or inducers of endoplasmic reticulum stress. SCFAs induced a dose-dependent and pertussis toxin-sensitive IL-8 response in bronchial epithelial cells, with a higher production of IL-8 in CFBE41o(-) than in 16HBE14o(-) cells. CONCLUSIONS This study illustrates that SCFAs contribute to excessive production of IL-8 in CF airways colonized with anaerobes via up-regulated GPR41.
Barriers and Facilitators to Participation in Work among Canadian Women Living with HIV/AIDS

Background. The impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) on the participation of women in paid/unpaid work is a little understood phenomenon. Purpose. A research study exploring the lived experiences of Canadian women's engagement in paid/unpaid work and the barriers and facilitators mediating this phenomenon. Method. Study design employed a phenomenological approach using data subanalysis of transcripts, double coded for agreement and to ensure saturation of themes. Results. Analysis of the data revealed an overarching theme of engagement mediated by interacting forces with eight subthemes: active management, agency constrained by structure, the nature of supports, HIV/AIDS sequelae, work as a galvanizing force, the presence of children, the element of fear, and negotiation of self. Implications. Insights gained indicate a need for further education, resources, supports, and policy changes at the systems level. Occupational therapy is positioned to broaden the role of rehabilitation in the context of HIV/AIDS, episodic disability, and work participation.
Regulation of SIVmac239 Basal Long Terminal Repeat Activity and Viral Replication in Macrophages

CCAAT/enhancer-binding protein (C/EBP) β and C/EBP sites in the HIV-1 long terminal repeat (LTR) are crucial for HIV-1 replication in monocyte/macrophages and for the ability of interferon β (IFNβ) to inhibit ongoing active HIV replication in these cells. This IFNβ-mediated down-regulation involves induction of the truncated, dominant-negative isoform of C/EBPβ referred to as liver-enriched transcriptional inhibitory protein (LIP). Although binding of the C/EBPβ isoform to C/EBP sites in the simian immunodeficiency virus (SIV) LTR has previously been examined, the importance of these sites in core promoter-mediated transcription, virus replication, IFNβ-mediated regulation, and the relative binding of the two isoforms (C/EBPβ and LIP) has not been investigated. Here, we specifically examine two C/EBP sites, JC1 (−100 bp) and DS1 (+134 bp), located within the minimal region of the SIV LTR, required for core promoter-mediated transcription and virus replication in macrophages. Our studies revealed that the JC1 but not DS1 C/EBP site is important for basal level transcription, whereas the DS1 C/EBP site is imperative for productive virus replication in primary macrophages. In contrast, either JC1 or DS1 C/EBP site is sufficient to mediate IFNβ-induced down-regulation of SIV LTR activity and virus replication in these cells. We also characterized the differential binding properties of C/EBPβ and LIP to the JC1 and DS1 sites. In conjunction with previous studies from our laboratory, we demonstrate the importance of these sites in virus gene expression, and we propose a model for their role in establishing latency and persistence in macrophages in the brain.
Cadmium Tolerance and Its Phytoremediation by Two Oil Yielding Plants Ricinus Communis (L.) and Brassica Juncea (L.) From The Contaminated Soil

The effect of increasing level of cadmium in soil was investigated on biomass production, antioxidants, Cd bioaccumulation and translocation in Ricinus communis vis-à-vis a commonly studied oil crop Brassica juncea. The plants were exposed to 25, 50, 75, 100, and 150 mg Cd/Kg soil for up to 60 days. It was found that R. communis produced higher biomass at all the contamination levels than that of B. juncea. Proline and malondialdehyde in the leaves increased with increase in Cd level in both the species, whereas soluble protein decreased. The bioaccumulation of Cd was higher in B. juncea on the basis of the per unit biomass, total metal accumulation per plant was higher in R. communis. The translocation of Cd from roots to shoot was also higher in B. juncea at all Cd concentrations. R. communis appeared more tolerant and capable to clean Cd contaminated soil for longer period in one sowing than B. juncea and the former can grow in wasteland soil also in which later cannot be cultivated.
Sensitivity and specificity of quantitative difference SPECT analysis in seizure localization.

UNLABELLED True ictal SPECT can accurately demonstrate perfusion increases in the epileptogenic area but often requires dedicated personnel waiting at the bedside to accomplish the injection. We investigated the value of perfusion changes as measured by ictal or immediate postictal SPECT in localizing the epileptogenic region in refractory partial epilepsy. METHODS Quantitative perfusion difference images were calculated by registering, normalizing and subtracting ictal (or immediate postictal) from interictal SPECT for 53 patients with refractory epilepsy. Perfusion difference SPECT results were compared with visually interpreted SPECT, scalp electroencephalography (EEG), MRI, PET and intracranial EEG. RESULTS In 43 patients (81%), discrete areas of increased perfusion (with ictal injections) or decreased perfusion (with postictal injections) were noted. Interictal scalp EEG was localizing in 28 patients (53%), ictal scalp EEG was localizing in 35 patients (66%) and intracranial EEG was localizing in 22 patients (85%) (of 26 patients who underwent invasive study). MRI was localizing in 34 patients (64%), PET was localizing in 32 of 45 patients (71%), interictal SPECT was localizing in 26 patients (49%) and peri-ictal SPECT (visual interpretation) was localizing in 30 patients (57%). By comparison with an intracranial EEG standard of localization, SPECT subtraction analysis had 86% sensitivity and 75% specificity. CONCLUSION Our data provide evidence that SPECT perfusion difference analysis has higher sensitivity and specificity than any other noninvasive localizing criterion and can localize epileptogenic regions with accuracy comparable with that of intracranial EEG. To obtain these results, one must apply knowledge of the timing of the ictal injection relative to seizure occurrence.
Postselection Thymocyte Maturation and Emigration Are Independent of IL-7 and ERK5

The transcription factor Krüppel-like factor 2 (KLF2) controls the emigration of conventional T cells from the thymus through its regulation of the cell surface receptor S1P1. Prior to KLF2 expression, developing T cells require a positive selection signal through the TCR. However, following positive selection there are time, spatial, and maturational events that occur before KLF2 is finally upregulated and emigration occurs. We are interested in determining the signals that upregulate KLF2 and allow thymocytes to emigrate into circulation and whether they are linked to functional maturation. In endothelial cells KLF2 expression has been shown to be dependent on the mitogen-activated protein kinase ERK5. Furthermore, it has been reported that IL-7 signaling leads to the phosphorylation of ERK5. Thus, we hypothesized that IL-7R signaling through ERK5 could drive the expression of KLF2. In this study, we provide evidence that this hypothesis is incorrect. We also found that CD8 lineage specification occurred normally in the absence of IL-7R signaling, in contrast to a recently proposed model. We showed that both CD4 and CD8 T cells complete maturation and express KLF2 independently of ERK5 and IL-7.
Implant Retention in Infected Joint Replacements: A Surgeon's Perspective

There is no standard treatment for infected joint replacements. The surgical options are varied and treatment choices may pose problems in relation to both efficacy and cost effectiveness. Surgical debridement combined with antibiotic therapy is an appealing option for surgeons and patients as it can lead to eradication of the infection with implant retention and good functional outcome. It avoids major revision surgery which can result in significant morbidity and mortality in an elderly group of patients. The author reviewed 73 patients with hip and knee periprosthetic infections and the data was analyzed in terms of outcome of primary treatment and final outcome, including bacteriology and prosthesis retention. Out of the 73 patients (53 hips and 20 knees), the majority (69%) were managed by primary surgical debridement followed by antibiotics and about one third (34%) lost their implants as a result of the infection. Retention of implants was higher in acute infections (85–100%) as opposed to late infections (20–50%). The microbiological analysis showed that Staphylococcus and Streptococcus caused the majority (76%) of infections. In this series, patients with an infected joint replacement had roughly the same probability (30%) of retaining the original prosthesis, undergoing a successful revision, or having no implants in situ at the end of treatment. (Int J Artif Organs 2008; 31: 804–9)
Endometrioid Stromal Sarcoma: A Clinicopathologic Study of 63 Cases

Endometrioid stromal sarcoma (also known as extrauterine endometrial stromal sarcoma [EESS]) is an uncommon tumor that occurs in women over a wide age range. The extrauterine location, non-gynecologic symptoms and signs at presentation, and confounding histologic features can pose a diagnostic challenge. In this study, we present the clinicopathologic features of 63 cases of EESS seen during a period of 21 years at our institution. Clinical information and pathology material were reviewed. Ages ranged from 27 to 87 years (median: 50 years). The most common symptoms and signs were an abdominal or pelvic mass, pain, vaginal bleeding, and gastrointestinal symptoms. The tumor size ranged from 1.2 to 24.5 cm. The most common sites of involvement were the ovaries (25), bowel wall (28), abdomen/peritoneum (37), pelvis (20), and vagina (6). Multiple sites were involved in 40 cases. Forty-six of 49 tumors had a classic microscopic appearance, and 3 had dedifferentiation; in 20 cases, there was vascular invasion. Fibroma-like stroma was seen in 30, hyaline plaques in 23, sex cord elements in 11, smooth muscle differentiation in 4, and myxoid change in 4 cases. Endometriosis was noted in 30 cases. Immunohistochemical results included: CD10 positivity in 31, desmin positivity in 9 (focal), estrogen receptor positivity in 28, and progesterone receptor positivity in 33 cases. In 25% of cases, an initial diagnosis other than EESS was made: sex cord-stromal tumors (4), gastrointestinal stromal tumor (3), leiomyosarcoma (3), liposarcoma (1), müllerian adenosarcoma (1), synovial sarcoma (1), malignant peripheral nerve sheath tumor (1), small round blue cell tumor (1), and atypical stromal endometriosis (1). Primary treatment was cytoreductive surgery for 61 patients and hormonal therapy for 2 patients. Adjuvant treatment included hormonal therapy, chemotherapy, and radiation therapy. Follow-up (5 to 336 months) information was available for 53 patients: alive with no evidence of disease, 29; alive with disease, 15; and dead of disease, 9 (median period of 70 months from diagnosis to death). Thirty-three patients had recurrent disease, and 10 patients were lost to follow-up. EESS is commonly associated with endometriosis and tends to be indolent with a propensity for recurrence. Seven of 9 patients who died of the disease had bowel involvement, and 3 had tumors with dedifferentiation. Besides the latter, no other histologic finding correlated with the clinical behavior of these tumors.
Mitochondrial DNA deletions in mitochondrial cytopathies

Among 56 patients with mitochondrial myopathies or cytopathies, 19 had large-scale deletions of mitochondrial DNA (mtDNA). Consistent with previous observations, all 19 had progressive external ophthalmoplegia and 12 had complete or partial Kearns-Sayre syndrome. One of two patients in whom mitochondrial rather than whole muscle DNA was analyzed had multiple populations of deleted mtDNA (dmtDNA). In all patients, the length of dmtDNA was inversely related to age of onset, but was not related to multiplicity of organ involvement. Patients with >50% dmtDNA tended to have an earlier onset of symptoms and a higher proportion of ragged-red fibers and cytochrome c oxidase (CCO)-negative fibers than patients with <50% dmtDNA, but these differences did not reach statistical significance. In some patients, CCO-negative fibers were more abundant than ragged-red fibers, indicating that the distribution of abnormal mitochondria can be more widespread than suggested by the frequency of ragged-red fibers. In biochemical assays, citrate synthase activity was a better reference for detecting defects in the respiratory complexes than the wet weight of muscle. Using this reference, 10 of 14 patients had one or more respiratory complex defects, and 74% of the observed defects could be correlated with an appropriate mtDNA deletion.
Prophylactic knee bracing in college football

American football can be harmful to knees. In an at tempt to reduce the number and severity of knee injuries, the intercollegiate football team at the Univer sity of Arizona (Pacific Ten Conference) has been using protective braces since 1981. Objective evaluation of the effectiveness of this program is the purpose of this study. All linemen, offensive and defensive, as well as linebackers and tight ends were considered to be the players at greatest risk and were required to use the braces. The brace used was the Anderson Knee Sta bler. Each player at each practice session or game was counted as one exposure. During the 4 years of brace use, there were 28,191 exposures, while the control group numbered 29,293 exposures. The data were analyzed from the perspectives of days lost from prac tice or games, player's position, the type and severity of injury, and the rate of injury per 100 players per season. Players at risk showed no trend to change in injury rate. Of the players at risk, the type and severity of injury in nonbraced and in braced groups were similar. A significant finding in players at risk was a two fold increase in knee ligament injury rate per 100 players when compared to rates for an entire team. The number of season-ending injuries remained unchanged. Prac tice time missed for third-degree medial ligament, and for medial meniscus injuries, was significantly lower in the braced group, but this was due to improved treat ment techniques initiated in 1981. Seven NCAA rule changes, directed at reducing knee injuries, have been introduced since 1981. Neither the rule changes nor the braces nor the combination thereof have had any apparent effect on the trend to knee injury in this study. We conclude that, in this study, knee injury prevention in a college football team was not improved by prophy lactic knee bracing.
The steroid interaction site in transmembrane domain 2 of the large conductance, voltage- and calcium-gated potassium (BK) channel accessory β1 subunit

Large conductance, voltage- and calcium-gated potassium (BK) channels regulate several physiological processes, including myogenic tone and thus, artery diameter. Nongenomic modulation of BK activity by steroids is increasingly recognized, but the precise location of steroid action remains unknown. We have shown that artery dilation by lithocholate (LC) and related cholane steroids is caused by a 2× increase in vascular myocyte BK activity (EC50 = 45 μM), an action that requires β1 but not other (β2–β4) BK accessory subunits. Combining mutagenesis and patch-clamping under physiological conditions of calcium and voltage on BK α- (cbv1) and β1 subunits from rat cerebral artery myocytes, we identify the steroid interaction site from two regions in BK β1 transmembrane domain 2 proposed by computational dynamics: the outer site includes L157, L158, and T165, whereas the inner site includes T169, L172, and L173. As expected from computational modeling, cbv1+rβ1T165A,T169A channels were LC-unresponsive. However, cbv1 + rβ1T165A and cbv1 + rβ1T165A,L157A,L158A were fully sensitive to LC. Data indicate that the transmembrane domain 2 outer site does not contribute to steroid action. Cbv1 + rβ1T169A was LC-insensitive, with rβ1T169S being unable to rescue responsiveness to LC. Moreover, cbv1 + rβ1L172A, and cbv1 + rβ1L173A channels were LC-insensitive. These data and computational modeling indicate that tight hydrogen bonding between T169 and the steroid α-hydroxyl, and hydrophobic interactions between L172,L173 and the steroid rings are both necessary for LC action. Therefore, β1 TM2 T169,L172,L173 provides the interaction area for cholane steroid activation of BK channels. Because this amino acid triplet is unique to BK β1, our study provides a structural basis for advancing β1 subunit–specific pharmacology of BK channels.
Support and continuity during the first 2 weeks postpartum.

OBJECTIVES To investigate mothers' perceived satisfaction with support from antenatal care (AC), postpartum care (PC) and child health care (CHC), respectively, during the first two weeks after childbirth. DESIGN Cross-sectional survey, mixed-method design. ETHICAL ISSUES The study was approved by the Regional Research and Ethics Committee at the Karolinska Insititutet, Sweden. METHODS Data were collected using a study-specific questionnaire that focused on mothers' satisfaction with support from AC, PC and CHC during the first 2 weeks after childbirth. All mothers in Stockholm County (n = 546) who gave birth to a live infant during a 1-week period in 2009 were invited to participate. Descriptive and logistic regression analyses and a content analysis were performed. RESULTS A large discrepancy was found between levels of satisfaction with AC, PC and CHC. Mothers were satisfied with the support from CHC healthcare nurses, but missed follow-up contact from AC and PC midwives. Nearly 40% of all mothers commented on insufficient support including that continuity in the chain of care was lacking and support for mothers' physical and emotional health was insufficient. Delivery at <37 weeks of gestation was associated with reduced satisfaction with both AC and CHC, but not with PC. Mothers who made emergency visits during the first two weeks were more likely to be dissatisfied with support from PC. CONCLUSION All links in the chain of care are important for the support of mothers during the first 2 weeks after childbirth, but continuity needs to be improved to raise the quality of care for mothers.
Adherence to Medications by Patients After Acute Coronary Syndromes

BACKGROUND Nonadherence to medication may lead to poor medical outcomes. OBJECTIVE To describe medication-taking behavior of patients with a history of acute coronary syndromes (ACS) for 4 classes of drugs and determine the relationship between self-reported adherence and patient characteristics. METHODS Consenting patients with the diagnosis of ACS were interviewed by telephone approximately 10 months after discharge. The survey elicited data characterizing the patient, current medication regimens, beliefs about drug therapy, reasons for discontinuing medications, and adherence. The survey included the Beliefs About Medicine Questionnaire providing 4 scales: Specific Necessity, Specific Concerns, General Harm, and General Overuse, and the Medication Adherence Scale (MAS). Multivariate regression was used to determine the independent variables with the strongest association to the MAS. A p value ≤0.05 was considered significant for all analyses. RESULTS Two hundred eight patients were interviewed. Mean ± SD age was 64.9 ± 13.0 years, with 60.6% male, 95.7% white, 57.3% with a college education, 87.9% living with ≥1 other person, and 42% indicating excellent or very good health. The percentage of patients continuing on medication at the time of the survey category ranged from 87.4% (aspirin) to 66.0% (angiotensin-converting enzyme inhibitors). Reasons for stopping medication included physician discontinuation or adverse effects. Of patients still on drug therapy, the mean MAS was 1.3 ± 0.4, with 53.8% indicating nonadherence (score >1). The final regression model showed R2 = 0.132 and included heart-related health status and Specific Necessity as significant predictor variables. CONCLUSIONS After ACS, not all patients continue their drugs or take them exactly as prescribed. Determining beliefs about illness and medication may be helpful in developing interventions aimed at improving adherence.
The evolution of the star formation rate function and cosmic star formation rate density of galaxies at z ∼ 1–4

We investigate the evolution of the galaxy star formation rate function (SFRF) and cosmic star formation rate density (CSFRD) of z ˜ 1-4 galaxies, using cosmological smoothed particle hydrodynamic (SPH) simulations and a compilation of ultraviolet (UV), infrared (IR) and Hα observations. These tracers represent different populations of galaxies with the IR light being a probe of objects with high star formation rates and dust contents, while UV and Hα observations provide a census of low star formation galaxies where mild obscuration occurs. We compare the above SFRFs with the results of SPH simulations run with the code P-GADGET3(XXL). We focus on the role of feedback from active galactic nuclei (AGN) and supernovae in form of galactic winds. The AGN feedback prescription that we use decreases the simulated CSFRD at z < 3 but is not sufficient to reproduce the observed evolution at higher redshifts. We explore different wind models and find that the key factor for reproducing the evolution of the observed SFRF and CSFRD at z ˜ 1-4 is the presence of a feedback prescription that is prominent at high redshifts (z ≥ 4) and becomes less efficient with time. We show that variable galactic winds which are efficient at decreasing the SFRs of low-mass objects are quite successful in reproducing the observables.